37 results about "Pharmaceutics technology" patented technology

The invention relates to the field of amino acid polypeptide and medicated diet and food treatment particles series health-care soup. Every 100 parts of finished product contain the following components in parts by weight: 30-95 parts of conventional bone and flesh stewed soup stock, 5-30 parts of amino acid polypeptide particles 0-20 parts of medicated diet and food treatment particles, 0-20 parts of meat particles, 0.02-6 parts of seasoning agent, 0.02-6 parts of stabilizer and the balance of water. A meat amino acid polypeptide anzymolysis technology, a conventional medicated diet and food treatment technology, an advanced beverage production technology, an advanced pharmacy technology and a new packaging technology are combined, and a new field for application of meat foods is created. The invention has the real intention that: a series of particle-containing health-care soup and health-care essence rich in amino acid polypeptide and medicated diet and food treatment particles is available on the most food and beverage markets in the form of upgrading nutritional beverage to fourth-generation nutritional health-care beverage different from the forms of functional beverage, health-care food beverage and protein-containing milk nutritious food beverage. Self-heating and easy-pull package is adopted, so that a product of the health-care soup integrates smooth mouthfeel, high nutrition absorption, convenience and fashion, various healthy and sub-healthy crowds and middle and old age crowds can drink hot high-nutrition health-care soup even in the field in winter, and broad market development prospect is realized.

The invention belongs to the technical field of pharmacy, and relates to a membrane separation method and device for recycling ceftazidime mother liquor. Ceftazidime belongs to a third generation antibiotics and has wider application than other third generation cephalosporin antibiotics. In a present production process of ceftazidime, due to the salting-out effect of the mother liquor in the crystallization process, the yield of ceftazidime is only 82%, 18% of ceftazidime is still in the mother liquor, and therefore not only is the production cost increased, but also certain pollution to the environment is caused. According to the membrane separation method and device for recycling the ceftazidime mother liquor, by utilizing the membrane separation technology and the adjustment of the process, the products in the mother liquor can be recycled, the production cost can be saved greatly, and pollution to environment can be reduced; besides, the device is simple to operate so that industrial amplification can be achieved easily.

The present invention discloses a parecoxib sodium impurity S, namely, N-{3-[(5-methyl-4-phenylisoxazol-3-yl)phenyl]sulfonyl}propionamide, and an preparation method thereof, and belongs to the technical field of chemical pharmacy. The method comprises the following steps: 5-methyl-3,4-diphenylisoxazole is used as a starting raw material, and the reaction conditions and an auxiliary reagent are controlled to increase the ratio of a sulfonyl chloride group connected to the meta-position of a phenyl ring at a 3-position of an isoxazole ring; and an amination reaction is performed, a crystallization mother liquid is concentrated to dryness, the obtained product is subjected to propionylation, and finally through preparative liquid chromatography separation, the parecoxib sodium impurity S is obtained. The high-purity parecoxib sodium impurity S provided by the present invention can be used as an impurity standard product in the detection and analysis of a finished product of parecoxib sodium, so that the accurate positioning and chemical composition determination of impurities in the detection and analysis of the finished product of the parecoxib sodium are promoted, reinforcement of control of the impurities is facilitated, and the quality of the finished product of the parecoxib sodium is further improved. The method provided by the invention has the advantages of cheap and easyraw materials, simple operation, good reproducibility, and an HPLC purity of 99.5% or more.

The invention belongs to the technical field of pharmacy, and specifically relates to stomach bismuth-magnesium granules and a preparation method thereof. The stomach bismuth-magnesium granules are granules prepared by combining main medicines namely bismuth aluminate, heavy magnesium carbonate, sodium bicarbonate, extractum glycyrrhizae powder, Frangulae cortex, fennel, aloe and rhizoma acori graminei, and then adding pharmaceutic adjuvants, wherein the volatile oil extracted from rhizoma acori graminei is included by starch sodium octenylsuccinate to obtain an inclusion compound, and then the inclusion compound is combined with other components. In the preparation method disclosed by the invention, the volatile oil extracted from rhizoma acori graminei is included by starch sodium octenylsuccinate, so that the volatile components of rhizoma acori graminei in the stomach bismuth-magnesium granules are not liable to volatilize, and the utilization rate of the volatile oil is high and superior to that of a beta-cyclodextrin method in the prior art; moreover, the curative effect of the stomach bismuth-magnesium granules prepared by the method is superior to that of the stomach bismuth-magnesium granules prepared by a rhizoma acori graminei cyclodextrin inclusion compound in the prior art.

The invention provides a small molecular activator taking human M2 type pyruvate kinase (M2 type pyruvate kinase, PKM2) as a target spot and application of the small molecular activator, and belongs to the technical field of pharmacy. According to the small molecular activator, the PKM2 is taken as the target spot, and the small molecule activator is screened by combining virtual screening based on butt joint and in-vitro biological activity evaluation. In-vitro activity test results show that two screened compounds have good PKM2 activation activity and good cancer cell inhibition activity, and discovered small molecules can provide a basis for research and development of new drugs for treating PKM2 related diseases, such as cervical cancer, breast cancer, ovarian cancer, prostate cancer,liver cancer, lung cancer, pancreatic cancer, colorectal cancer, leukemia, melanoma and multiple myeloma. A lead compound of the small molecular activator can be further optimized in structure, and arelatively good application prospect is achieved.

The invention discloses a preparation method of imidocarb dipropionate and an intermediate thereof and belongs to the technical field of chemical pharmacy. According to the method, m-nitrobenzonitrilereacts with ethylenediamine with sodium sulfide taken as a catalyst; palladium on carbon-ammonium formate reduction is performed; a product and urea are subjected to condensation reaction, so that imidazole phenylurea dihydrochloride can be obtained; dissociated imidazole phenylurea reacts with propionic acid, so that the imidazole phenylurea dipropionate can be obtained. The method has the advantages o reduced wastes, cheap and easily available raw materials, simple operation, high product yield, simple process operation and high safety, and is suitable for industrial production.

The invention relates to the technical field of pharmaceutics and discloses the application of the compound AM-1241, namely (R,S)-3-(2-iodo-5-nitrobenzene formyl)-1-(1-methyl-2-piperidinyl methyl)-1H-indol to preparation of a drug for treating Parkinson's disease. According to the compound, a cannabinoid receptor CB2 is used as the effective target spot of Parkinson's disease treatment, and symptoms of Parkinson's disease can be relieved greatly; furthermore, a molecular mechanism shows that CB2 expression of substantia nigra and hippocampus are activated, the occurrence rate of neuronal apoptosis is reduced, and a remarkable neuroprotective effect is realized; besides, by preparing the compound into solid lipid nanoparticle preparations for administration, drug absorption rate and brain-targeting effect can be improved, so that Parkinson's disease treatment effect is further improved. It is expected to prepare the drug for treating Parkinson's disease with the compound as the effective constituent, and the drug can become the substitution of existing levodopa drugs.

Belonging to the technical field of biology and pharmacy, the invention relates to a serum / plasma miRNA marker related to drug-induced liver injury (DILI) and application of its detection kit in early detection of DILI as well as drug liver toxicity safety evaluation, etc. The marker can be one or more of miR-122, miR-192 and miR-193. The detection kit of the marker is conducive to early detection of DILI, and has better early sensitivity than traditional blood biochemical indexes. Thus, the detection kit has potentials to be applied in preclinical laboratories as well as clinical diagnosis of various hospitals nationwide, and simultaneously provides a powerful reference for liver toxicity safety evaluation during new drug development, as well as improves the detection rate of drug liver toxicity to a greater extent.

The invention discloses application of apatinib and a combination of the apatinib and CCI-779 in preparation of drugs for preventing and treating small cell lung cancer, and relates to the technical field of pharmacy. In-vitro tests prove that the apatinib has a concentration-dependent characteristic on the action of a small cell lung cancer cell strain (NCI-H446), and high-concentration apatinibcan inhibit cell proliferation and migration of the small cell lung cancer cell strain and induce cell apoptosis, and can improve the sensitivity of small cell lung cancer cells to the apatinib when combined with an mTOR inhibitor CCI-779, and can inhibit proliferation and migration of the small cell lung cancer cells at a relatively low concentration to cause cell cycle arrest and induce cell apoptosis.

The invention discloses a drying machine suitable for powder mixing and a drying method of the drying machine, and belongs to the technical field of biological pharmacy. The drying machine comprises a base, a drying barrel, stirring blades, a driving motor and a vibrating mechanism; the stirring blades are located in the drying barrel; the vibrating mechanism comprises a vibrating platform and an impact hammer; the vibrating platform is located above the base, and the drying barrel is mounted on the upper surface of the vibrating platform; the impact hammer is rotationally mounted on the base; the top of the impact hammer makes contact with the lower surface of the vibrating platform; an output shaft of the driving motor is connected with the bottom of the impact hammer; the top of the impact hammer is connected with the stirring blades in the impact hammer. The driving motor drives the impact hammer to act, the impact hammer continuously impacts the vibrating platform, the drying barrel vibrates, and therefore the medicinal powder attached to the inner wall of the drying barrel can fall to the bottom of the drying barrel; meanwhile, the driving motor drives the stirring blades to rotate, the medicinal powder in the drying barrel is mixed, the mixing efficiency is high, and the heating and drying time is short.

The invention provides a separation and purification device for biopharmacy, relates to the technical field of biopharmacy, and solves the problem that rapid fishing of traditional Chinese medicine straws cannot be realized through structural improvement, and a fishing structure can enhance the purification efficiency and effective dissolution of traditional Chinese medicine liquid and additives; even heating of the bottom of a barrel body cannot be achieved, and a heating structure cannot be organically combined with a purification strengthening structure. The separation and purification device for biological pharmacy comprises the barrel body, a slag removing structure is mounted in the barrel body, a mixing structure is further mounted in the barrel body, and a stirring structure is mounted on the barrel body. A rotating shaft B is rotationally connected to the barrel body, and a handle is welded to the rotating shaft B; a stirring plate is welded to the rotating shaft B, after the stirring plate rotates by 90 degrees, the stirring plate makes elastic contact with the stress plate, at the moment, the cleaning plate is flush with the cleaning pipe, and therefore cleaning of the traditional Chinese medicine straw can be completed through the scraping plate.

The invention belongs to the technical field of pharmacy, and particularly relates to a composite medicine and a preparation method and application thereof. The invention relates to a composite medicine, the composite medicine at least comprises red blood cells and artesunate, and the artesunate is entrapped in the red blood cells. Compared with the traditional artesunate injection, the composite medicine disclosed by the invention can realize slow release of the medicine after entering the body, the medicine effect can be maintained for about 9 days, the composite medicine has an obvious slow release effect, and the problems of rapid reduction of the blood concentration of the traditional artesunate injection and side effects caused by short-time multiple administration can be solved, so that malaria can be effectively prevented or treated.

The invention discloses benzenesulfonamide phenylbutyric acid podophyllotoxin carboxylic ester derivatives as well as a synthesis method and application thereof, belongs to the technical field of chemical pharmacy. The invention particularly relates to podophyllotoxin derivatives and application thereof in tumor inhibition. Corresponding benzene sulfonamide phenylbutyric acid is connected with podophyllotoxin through a synthesis means to obtain corresponding ester derivatives, and in-vitro anti-tumor activity research shows that the podophyllotoxin carboxylic ester derivatives have very strong inhibitory activity on tumor cell strains.

The invention relates to a preparation method of a traditional Chinese medicine effective part for treating endoxemia, belonging to the technical field of Chinese medicine production. The preparation method comprises the following steps of: crushing dry scirpus yagara ohw tubers, adding 85% ethanol-water solution three times amount of the material, soaking for 24 hours, then carrying out reflux extraction for 2 times, wherein each reflux extraction lasts for 2 hours, filtering, combining extracting solutions and concentrating; adding water, the volume of which is 1.5 times of the volume of the concentrated extracting solution, to the concentrated extracting solution, respectively extracting by using extracting solvents, the polarities of which are from small to large, thus obtaining extract liquor, then concentrating, passing through a normal phase column for chromatography, and eluting by using an elution solvent; drying the collected eluant so as to obtain the scirpus yagara ohw effective part. According to the preparation method, the collected extracting solvent in the extract liquor is ethyl acetate, and the eluant solvent at least comprises an elution solvent formed by petroleum ether and ethyl acetate in a volume ratio of 100: 1, 100: 10 or 100: 12. Pharmacology experiments prove that the scirpus yagara ohw effective part prepared by the method has very good anti-endoxemia effect.

The invention relates to the technical field of pharmaceuticals, and discloses traditional Chinese medicine decoction piece processing equipment and a processing method thereof. The traditional Chinese medicine decoction piece processing equipment comprises a fixing plate; front and rear side faces of the fixing plate are fixedly connected with front and rear side plates; grooves are formed in the right sides of the front and rear side plates and a sliding side plate is arranged in each groove in a sleeved manner; four sets of bottom plates A and bottom plates B are arranged on the front and rear side plates in a sleeved manner; the bottom plates A and the bottom plates B are arranged, and in the process of processing medicinal materials by the equipment, continuous switching between a corrugated state and a transverse state can be formed; in the corrugated state, a better cleaning effect on the medicinal materials can be achieved with the cooperation of sharp protrusions and pressing and pushing of a brush plate on the medicinal materials; sharp ends of connecting pads can conform to recesses in the medicinal materials through deformation after being in contact with the medicinal materials, so that wrinkles on the medicinal materials are cleaned, and the cleaning effect is improved; and the equipment can be in the transverse state after rubbing once, so that rubbed off impurities are accommodated in the connecting pads and are discharged alone, thus avoiding the problem that the impurities are adhered to or embedded into the medicinal materials in subsequent rubbing.

The invention discloses biopharmaceutical equipment convenient to clean, which belongs to the technical field of biopharmaceuticals. The equipment comprises a stirring box, a stirrer, a moving part, acleaning part, two collecting parts and a flushing part, wherein the stirring box is rectangular; a base is arranged below the stirring box; the stirring box, the moving part and the cleaning part are all arranged above the base; the stirring box is provided with a Y-shaped feeding port; two discharging ports are formed in the lower portion of the stirring box; the stirrer is arranged in the stirring box; the moving part is located on one side of the stirring box; the cleaning part is located on the other side of the stirring box; the two collecting components correspond to the two discharging ports in the lower portion of the stirring box respectively; the flushing part is located on one side of the base. The stirrer and the stirring box are cleaned more thoroughly through cooperation ofthe parts, and compared with traditional cleaning, the cleaning efficiency is higher.

The invention relates to the technical field of pharmacy, in particular to a purification method based on gonadotropin in urine. The invention relates to a purification method based on gonadotropin in urine. The purification method comprises the following steps: S1, collecting urine and carrying out dialysis treatment; s2, carrying out chromatography and collecting an eluent; s3, separating; and S4, further processing. According to the purification method based on the gonadotropin in the urine, the gonadotropin obtained through purification has the advantages of being high in titer and purity, and the prepared gonadotropin injection preparation does not cause adverse reactions such as pain or erythema.

The invention discloses a stirring processing equipment for biopharmaceuticals, which belongs to the technical field of biopharmaceuticals. The stirring box is driven by the follower on the second stirring box to perform rotating centrifugal stirring. The first stirring box is connected with the centrifugal stirring box through a connecting pipe, and the material once stirred by the first stirring box enters the centrifuge. The stirring box performs secondary stirring and overflows from the centrifugal stirring box into the second stirring box, and finally completes the discharge from the discharge port at the bottom of the second stirring box; the top of the first stirring box is provided with a motor, and the motor The output shaft of the output shaft is connected with the main shaft extending into the first mixing box, the main shaft is provided with a driving part, the driving part is located above the first mixing box, the driving part cooperates with the driven part and drives the driven part to rotate Thereby, the centrifugal stirring of the centrifugal stirring box is realized.

A biopharmaceutical capsule filling device, which relates to the technical field of biopharmaceuticals. The capsule body is provided with a first capsule head and a second capsule head. The first capsule head or the second capsule head is provided with a drug feeding tube. There is a sealing film and a drug sealing tray, and a pull rod is arranged in the drug feeding tube, and the pull rod passes through the sealing film and is connected with the sealing gasket in the capsule body; It is filled into the capsule, and the occurrence of defective products is greatly reduced. At the same time, the heating link is missing, which greatly reduces the production cost.

The invention relates to a compound platycodon grandiflorum cough-stopping solution preparation for inhalation and a preparing method thereof, and belongs to the field of the pharmaceutics technology.The solution preparation is prepared from traditional Chinese medicine raw materials (platycodon grandiflorum, honey-stir-baked radix polygalae, honey-stir-baked flos farfarae and licorice root) andauxiliary materials (an isotonic agent and a solvent), wherein the consumption ratio of platycodon grandiflorum to honey-stir-baked radix polygalae to honey-stir-baked flos farfarae to licorice root used in the compound platycodon grandiflorum cough-stopping solution preparation for inhalation is (80-200):(20-60):(10-30):(5-20). The compound platycodon grandiflorum cough-stopping solution preparation for inhalation can rapidly form aerosol through an atomizer, the formed aerosol can directly and rapidly act on an affected part, and the medicine acting on the affected part can be rapidly absorbed to have an effect; the use dosage is small, the effect is rapidly realized, the treatment effect is good, and no other toxic or side effects exist.

The invention belongs to the technical field of pharmacy, and particularly relates to a preparation method of a clonazepam related substance B. The preparation method of the clonazepam related substance B provided by the invention comprises the following steps: dissolving chloride into a protonic solvent, adding an acid-binding agent, reacting at room temperature until the reaction is finished, and filtering to obtain a target compound. The protonic solvent is any one of methanol, ethanol and isopropanol; the acid-binding agent is any one of ammonia water and an ammonia methanol solution. According to the method, commercially available chlorides are used as starting materials, and a high-yield and high-purity clonazepam related substance B can be obtained through cascade reaction. The method provided by the invention is simple in operation steps, and after a crude product is obtained through filtration, the related substance B which is high in purity and meets the requirements of pharmacopoeia can be obtained without post-treatment purification such as recrystallization and the like. According to the clonazepam related substance B obtained by the method disclosed by the invention, the quality of a clonazepam product and the production safety and effectiveness are ensured.

The invention relates to a preparation method of aminothiazole acetyloxime acid with a controllable particle size, and belongs to the technical field of chemical pharmacy. The preparation method comprises the following steps: ahydrolysis step: hydrolyzing ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate serving as a raw material to generate a compound 1; an acylation step: dropwisely adding an acylating agent into the system to perform acylation reaction to obtain a compound 2; and a crystallization step: adding activated carbon into the reaction system for decolorization, then dropwise adding an acidic solution into the system at different temperatures to control the pH value of the system, and after the solid is separated out, carrying out centrifugal drying to obtain a compound 3 with controllable particle size. According to the method, by controlling different acid liquor adding temperatures, the particle size of the prepared aminothiazole acetyloxime acid is controllable; and the technological process is simple to operate and suitable for industrial production.

The invention relates to a control method of ethanol residues in chondroitin sulfate and belongs to the technical field of chemical pharmacy. Chondroitin sulfate with precipitated ethanol is crushed into particles with the diameter not larger than 2 mm and dehydrated with ethanol with the gradually increasing concentration, the ethanol in chondroitin sulfate precipitates is sucked, and chondroitin sulfate is placed in a plate, then placed in a hot air circulating oven, firstly heated to 55-65 DEG C and then dried for 3 h; chondroitin sulfate is heated to 75-88 DEG C after the plate is turned and dried until the moisture is up to the standard, and a chondroitin sulfate product with the ethanol content smaller than 1,000 ppm is obtained. The method has the benefits as follows: chondroitin sulfate is gradually dehydrated with ethanol with the gradually increasing concentration, and the treated chondroitin sulfate precipitates can be quickly dried to have very low ethanol residue level with a common hot air circulating oven instead of a vacuum oven; the technology facilitates enlarged production, requires no additional equipment and is easy to operate.

The invention belongs to the technical field of traditional Chinese medicine and particularly relates to a traditional Chinese medicine preparation for treating facial paralysis. The traditional Chinese medicine preparation is an orally taken preparation which is prepared from rhizoma gastrodiae, rhizoma arisaematis, fructus arctii, scorpion, centipede, bombyx batryticatus, unprocessed rhizoma pinelliae and auxiliary materials with a conventional pharmaceutic technology. According to the traditional Chinese medicine preparation, the rigorous prescription is formed according to the compatibility theory of monarch, minister, assistant and guide in traditional Chinese medicine, the preparation has pure taste and special effect, and the whole prescription has functions of expelling wind to dredge collaterals, removing stagnation, eliminating swelling, removing blood stasis, reducing phlegm, clearing away heat and relieving pain, so that treatment of facial paralysis is realized; clinical data shows that the traditional Chinese medicine preparation has good treatment effect on facial paralysis, and the total effective rate is 94%.

The invention discloses a post-treatment method for preparing sitagliptin by an enzymic method and sitagliptin free alkali, belonging to the technical field of chemical pharmacy. The method comprisesthe following steps: acidifying a reaction solution for preparing sitagliptin via the enzyme method, and removing enzymes, impurities and unreacted raw materials; adjusting the pH value of a residualreaction solution to 5-9, evaporating out water, and removing an organic solvent dissolved in water; conducting cooling, adjusting the pH value of the residual reaction solution to 11-13 so as to realize material solidification and dispersion, performing suction filtration, and then conducting drying to obtain the sitagliptin free alkali. The method is high in stability, simple to operate and lowin cost, high-purity and high-yield sitagliptin free alkali solid powder can be obtained, wastewater treatment is facilitated, and the method is suitable for industrial production.

The invention relates to an apixaban and fumaric acid eutectic and a preparation method and application thereof, and belongs to the technical field of chemical pharmacy. By using Cu-Kalpha radiation, the X-ray powder diffraction pattern of apixaban and fumaric acid disclosed by the invention has characteristic peaks at positions with diffraction angles 2 theta of 5.7 + / -0.2 degrees, 7.2 + / -0.2 degrees, 8.7 + / -0.2 degrees, 11.4 + / -0.2 degrees, 13.2 + / -0.2 degrees, 16.5 + / -0.2 degrees, 17.6 + / -0.2 degrees, 18.5 + / -0.2 degrees, 20.1 + / -0.2 degrees, 20.7 + / -0.2 degrees, 21.9 + / -0.2 degrees, 23.2 + / -0.2 degrees and 25.1 + / -0.2 degrees. The prepared eutecticum of apixaban and fumaric acid is good in physical stability and chemical stability, and meanwhile, compared with an apixaban N-1 anhydrous crystal form, the dissolution rate is remarkably improved, so that the in-vivo bioavailability is further improved.

The invention belongs to the technical field of pharmacy, and particularly discloses a gynecological leucorrhea arresting sustained release tablet and a preparation method thereof. The gynecological leucorrhea arresting sustained release tablet is composed of main drugs and pharmaceutic adjuvants, the main drugs are composed of cortex ailanthi, cortex phellodendri, Chinese yam, poria cocos, tortoise shells, donkey-hide gelatin and schisandra chinensis, and the pharmaceutic adjuvants comprise a surfactant, an adhesive, a lubricant and a filler. The medicine is prepared into the sustained-release preparation, the action time of the medicine in the body can be effectively prolonged, the medicine taking dosage and frequency of a patient are reduced, meanwhile, stains on the surfaces of the raw materials can be comprehensively removed by classifying and screening the raw materials and comprehensively cleaning and dipping the raw materials, and the cleanliness of the surfaces of traditional Chinese medicine is improved; the traditional Chinese medicinal materials are effectively extracted in the extraction process, the content of effective components of the medicine is reserved, the purity of the effective components of the medicine is kept, and the medicinal value and quality of the prepared gynecological leucorrhea stopping sustained release tablet are further improved.

The invention belongs to the technical field of pharmacy, and particularly relates to a musk ketone preparation method. A hot-pressing distiller adopted in the preparation method comprising a body, apartition plate is arranged in the body; the cross section of the partition plate is wavy, so that the heating area is increased; a distillation cavity is formed above the partition plate and is usedfor heating filter residues and filtrate; a feeding port is formed in one side of the top of the distillation cavity; a flow guide pipe is arranged in the center of the top of the distillation cavity,and the end, away from the body, of the flow guide pipe is communicated with a separation pipe; a valve is arranged at the bottom of the separation pipe, the top of the separation pipe is communicated with a condensation pipe, and the condensation pipe is sleeved with a cooling water pipe; a water outlet pipe is arranged at the top of the cooling water pipe, the bottom of the cooling water pipe is communicated with a water inlet pipe, and circulating cooling water is introduced into the cooling water pipe through cooperation of the water inlet pipe and the water outlet pipe; the heating areaof the distillation cavity is increased through the wavy partition plate, so that the heating efficiency of the distillation cavity is improved, fuel gas is saved, and the hot-pressing distillation extraction efficiency of filter residues and filtrate is improved.