CN103800297B - A kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof - Google Patents
A kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof Download PDFInfo
- Publication number
- CN103800297B CN103800297B CN201410054176.5A CN201410054176A CN103800297B CN 103800297 B CN103800297 B CN 103800297B CN 201410054176 A CN201410054176 A CN 201410054176A CN 103800297 B CN103800297 B CN 103800297B
- Authority
- CN
- China
- Prior art keywords
- praziquantel
- floating type
- composition
- type sustained
- release sheet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The invention belongs to technical field of medicine, disclose a kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof. This praziquantel composition in-stomach floating type sustained-release sheet comprises following supplementary material: the praziquantel of 65～85 weight portions, the HP-β-CD of 50～60 weight portions, the hydroxypropyl methylcellulose of 40～60 weight portions, 30～50 weight portion xanthans. Praziquantel composition in-stomach floating type sustained-release sheet slow release effect provided by the invention is good, and after administration, the plasma concentration curve of praziquantel is more mild, has significantly improved the bioavilability of praziquantel, is more conducive to the promotion and application of praziquantel.
Description
Technical field
The invention belongs to technical field of medicine, particularly a kind of praziquantel composition in-stomach floating typeSustained release tablets and preparation method thereof.
Background technology
Animal parasitosis is to invade by parasite the disease that body causes. After zoogenetic infection parasite,Pathological change mainly comprises the mechanical injuries of parasite polypide to host tissue, the toxin of polypide secretion orThe necrosis that enzyme causes, and the infiltration of the EC that causes of host response and other inflammatory cells,Even form EC's property abscess and the EC's property granuloma to larva or worm's ovum generation. MovingThing parasitic disease serious threat animal health, has brought huge harm to animal feeding, and some animal is postedInfested disease even can be propagated by people and animals. At present, for parasitic control, mainly adopt drug therapy,Praziquantel is one of conventional anti-parasite medicine.
Praziquantel (Praziquantel, PZQ) is a kind of isoquinoline compound, for the anti-fluke of wide spectrum andTapeworm medicine, the blood fluke, tapeworm, cysticercus, clonorchis sinensis, lung fluke that humans and animals is infected,Fasciolopsis is all effective. Praziquantel, has structure shown in formula I, and relative molecular mass is 312.42, is whiteLook or off-white color crystalline powder, fusing point is 136 DEG C～141 DEG C, is insoluble in water, is soluble in chloroform,Distribution coefficient in phosphate buffer and cyclohexane is 14:86, and oral have an excitant,
Although the mechanism of action of praziquantel is not also got across completely, existing evidence shows that it is mainBe by making the impaired two aspect generation effects of polypide spasm and cortex, be specially: praziquantel increases on the one handThe cationic permeability of polypide cell membrane, calcium ion content in polypide cortical cell is reduced, increaseThereby the picked-up of the calcium ion of intramuscular causes polypide spasm and destroys cephalomere; On the other hand, can cause polypide skin, there is cavity diabrosis in the damage of layer, causes polypide surface antigen to expose and attacked by host immune. GrindStudy carefully and show that praziquantel is mainly rapidly absorbed in small intestine, praziquantel is after absorption, first by passive diffusionFirst be distributed in liver, kidney, be distributed to rapidly afterwards whole body, its dynamic metabolism feature is liver " first mistakeEffect ", after oral absorption, rapidly by liver metabolism, and its metabolite does not have biologically active.
At present, only have a kind of Droncit, i.e. conventional tablet, when the application of this formulation first pass effect strong,Metabolite non-activity, bioavilability are low, have limited the promotion and application of praziquantel.
Summary of the invention
In view of this, goal of the invention of the present invention is to provide a kind of praziquantel composition in-stomach floating type slowRelease sheet and preparation method thereof. This praziquantel composition in-stomach floating type sustained-release sheet slow release effect is good, administrationThe plasma concentration curve of rear praziquantel is more mild, has significantly improved the bioavilability of praziquantel, more hasBe beneficial to the promotion and application of praziquantel.
In order to realize goal of the invention of the present invention, the present invention adopts following technical scheme:
The invention provides a kind of praziquantel composition in-stomach floating type sustained-release sheet, it comprises following weight portionSupplementary material:
HP-β-CD is inclusion material, can significantly improve the bioavilability of insoluble drug,And HP-β-CD is water-soluble large, good biocompatibility, local irritation is little, does not cause that immunity is anti-Should, security performance is compared other inclusion materials and is wanted high. The present invention is using HP-β-CD as inclusion materialExpect, can increase solubility and the dissolution rate of praziquantel, be conducive to praziquantel and dissolve fast in intestines and stomach,Improve the bioavilability of praziquantel.
Hydroxypropyl methylcellulose is cellulose derivative class hydrophilic gel matrix material, when it is applied to medicineWhen thing preparation, form layer of gel barrier in dosage surface, the proportion that maintains pharmaceutical preparation skeleton is less than stomachContent, makes medicine float on gastric juice top, and then makes medicine not be subject to the impact of gastric emptying, stagnant for a long timeStay in stomach. And the gel skeleton that hydroxypropyl methylcellulose forms also has the effect of storage of pharmaceutical,Make medicine slowly to gastric juice, move (diffusion or corrosion discharge) from gel skeleton, until the medicine of institute's loadDischarge completely.
Xanthans is natural gum class hydrophilic gel matrix material, and its slow-release capability is strong, without burst drug release effect,Medicine discharges favorable reproducibility. Hydroxypropyl in praziquantel composition in-stomach floating type sustained-release sheet provided by the inventionMethylcellulose and xanthans form composite material skeleton, have ensured praziquantel composition provided by the inventionIn-stomach floating type sustained-release sheet is long-time delay and good sustained release performance in stomach.
Praziquantel composition in-stomach floating type sustained-release sheet provided by the invention adopts HP-β-CD to doFor inclusion material, hydroxypropyl methylcellulose-xanthans forms skeleton as composite material, has significantly improvedThe dissolubility of praziquantel, has ensured the sustained release performance of this praziquantel composition in-stomach floating type sustained-release sheet, carriesThe high bioavilability of praziquantel.
In some embodiments of the invention, praziquantel composition in-stomach floating type sustained-release provided by the inventionSheet comprises the supplementary material of following weight portion:
Preferably, the supplementary material in praziquantel composition in-stomach floating type sustained-release sheet provided by the invention also wrapsDraw together a kind of in blowing agent, lubricant, diluent, glidant, bleach activator, flavouring agent or more than bothMixture.
Blowing agent produces gas, increases the aquation rate of framework material; When blowing agent is applied in slow release formulationTime, the gas that blowing agent produces can be adsorbed on the skeleton of gelation, makes tablet floating. ThisIn the bright praziquantel composition in-stomach floating type sustained-release sheet providing by adding blowing agent to make this sustained release tablets at stomachIn the interior short time, rise and float, further improved praziquantel composition in-stomach floating type sustained-release provided by the inventionThe performance of sheet.
When lubricant can make compressing tablet on the one hand, pressure distribution is even, improves the tablet uniformity, on the other hand canTo improve the outward appearance of tablet, make tablet surface light, smooth.
Diluent, also referred to as filler, for increasing the weight or volume of formulation, contributes to the shape of tabletBecome.
Glidant, for reducing the frictional force between particle, is more conducive to the preparation of tablet.
Bleach activator, the hydration rate of reduction framework material, the retentivity of raising sustained release tablets, has extended pyrroleQuinoline one compositions in-stomach floating type sustained-release sheet is in the time of Entogastric lingering.
Flavouring agent can improve the bad smell of medicine, is applied to the faunichron that dog, cat etc. have a sharp sense of taste,Can produce certain food calling effect. Experimental result shows, in praziquantel composition stomach provided by the inventionFloating slowly releasing sheet has food calling effect to animal, and convenient drug administration is more conducive to the popularization of praziquantel and makesWith.
In some embodiments of the invention, praziquantel composition in-stomach floating type sustained-release provided by the inventionIn sheet, blowing agent is a kind of in calcium carbonate, magnesium carbonate, sodium acid carbonate, lauryl sodium sulfate or bothAbove mixture.
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionIn sustained release tablets, lubricant is the one or two in dolomol, microcrystalline cellulose, tricalcium phosphate, sodium silicoaluminateThe above mixture of person.
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionIn sustained release tablets, diluent is a kind of or both the above mixing in lactic acid, starch, dextrin, pregelatinized starchThing.
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionIn sustained release tablets, glidant is the one in talcum powder, superfine silica gel powder, APEO lauryl alcohol sodium sulfovinateOr both above mixtures.
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionIn sustained release tablets, bleach activator is 18 alcohol.
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionIn sustained release tablets, flavouring agent is one in chicken essence, the fresh perfume (or spice) of liver, 902 meat perfume (or spice), 608 fish raw meat perfume (or spice), saccharin sodiumPlant or both above mixtures.
In some embodiments of the invention, praziquantel composition in-stomach floating type sustained-release provided by the inventionSheet comprises the supplementary material of following weight portion:
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionSustained release tablets comprises the supplementary material of following weight portion:
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionSustained release tablets comprises the supplementary material of following weight portion:
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionSustained release tablets comprises the supplementary material of following weight portion:
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionSustained release tablets comprises the supplementary material of following weight portion:
In other embodiment of the present invention, praziquantel composition in-stomach floating type provided by the inventionSustained release tablets comprises the supplementary material of following weight portion:
The present invention also provides a kind of preparation method of praziquantel composition in-stomach floating type sustained-release sheet, this pyrroleQuinoline one compositions in-stomach floating type sustained-release sheet comprises the supplementary material of following weight portion:
This preparation method comprises the following steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 26～34 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion,Dry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained blowing agent, step 1 gainedDiluent, mix with step 1 gained glidant, obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, through softwood processed, granulate,After dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
First preparation method provided by the invention adopts inclusion technique by part praziquantel and hydroxy propyl-Beta-ringDextrin carries out inclusion and obtains praziquantel inclusion compound, praziquantel inclusion compound can increase praziquantel solubility andDissolution rate, while having overcome insoluble drug as sustained release tablets, the slower shortcoming of dissolution rate in early stage.
In some embodiments of the invention, preparation method provided by the invention comprises the following steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 30 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion, dryDry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained blowing agent, step 1 gainedDiluent, mix with step 1 gained glidant, obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, through softwood processed, granulate,After dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 26～34 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion,Dry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained bleach activator, step 1 gainedBlowing agent, step 1 gained diluent, mix with step 1 gained glidant, obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, through softwood processed, granulate,After dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the following steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 30 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion, dryDry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained bleach activator, step 1 gainedBlowing agent, step 1 gained diluent, mix with step 1 gained glidant, obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, softwood processed, granulates, dryAfter dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 26～34 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion,Dry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained bleach activator, step 1 gainedBlowing agent, step 1 gained diluent, step 1 gained glidant, mix with step 1 gained flavouring agent,Obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, through softwood processed, granulate,After dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
In other embodiment of the present invention, preparation method provided by the invention comprises the steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 30 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion, dryDry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained bleach activator, step 1 gainedBlowing agent, step 1 gained diluent, step 1 gained glidant, mix with step 1 gained flavouring agent,Obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, through softwood processed, granulate,After dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
Preferably, in preparation method provided by the invention, in g/mL, hydroxy propyl-Beta-ring in step 2In dextrin in aqueous solution, the quality percent by volume of HP-β-CD is 20%～30%.
Preferably, in preparation method provided by the invention, in step 2, the time of inclusion is 3h～10h.
Preferably, in preparation method provided by the invention, in step 2, the temperature of inclusion is 45 DEG C～55 DEG C.
Preferably, in preparation method provided by the invention, before being dried after step 2 inclusion, also comprise coldHide operation, be specially under-4 DEG C～4 DEG C conditions and place 16h～20h. Inclusion gained solution is carried out coldAfter the processing of Tibetan, be convenient to inclusion compound separates out from solution.
Preferably, in preparation method provided by the invention, in step 4 in ethanol water, the body of ethanolLong-pending percentage concentration is 70%～90%.
Preferably, in preparation method provided by the invention, in L/kg, in step 4 ethanol water withThe volume mass ratio of the second product is 0.2～0.4:1.
Preferably, in preparation method provided by the invention, the order number of the sieve used of granulating in step 4 is 18Order～20 order.
Preferably, in preparation method provided by the invention, in step 4, dry temperature is 40 DEG C～60 DEG C.
The present invention also provides a kind of praziquantel composition in-stomach floating type sustained-release sheet, and its preparation method comprisesFollowing steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get step 1 gained HP-β-CD and mix with water, obtain HP-β-CD waterSolution; Get 26～34 weight portion step 1 gained praziquantels and the HP-β-CD aqueous solution through inclusion,Dry, pulverize, obtain the first product;
Step 3: step 1 gained praziquantel, the step 1 of getting step 2 gained the first product, surplusObtain hydroxypropyl methylcellulose, step 1 gained xanthans, step 1 gained blowing agent, step 1 gainedDiluent, mix with step 1 gained glidant, obtain the second product;
Step 4: get step 3 gained the second product and mix with ethanol water, through softwood processed, granulate,After dry, with step 1 gained mix lubricant, compressing tablet, to obtain final product.
The invention provides a kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof. This pyrroleQuinoline one compositions in-stomach floating type sustained-release sheet comprises following supplementary material: the praziquantel of 65～85 weight portions,The HP-β-CD of 50～60 weight portions, the hydroxypropyl methylcellulose of 40～60 weight portions, 30～50 weight portion xanthans. Release dynamics result of study shows, praziquantel composition stomach provided by the inventionIt is short that interior floating slowly releasing sheet works the time of floating, and continues the flotation time long, and sustained release performance is good; In body, in medicine generation, is movingMechanics study result shows, the blood medicine of praziquantel composition in-stomach floating type sustained-release sheet provided by the invention is denseThe line of writing music is more mild, and the effective blood drug concentration time remains longer, has significantly improved the biology profit of praziquantelExpenditure, is more conducive to the promotion and application of praziquantel.
Brief description of the drawings
Fig. 1 shows average blood concentration-time graph that in embodiment 13, A organizes and B organizes, and wherein 1 is AGroup, the i.e. average blood concentration-time graph of praziquantel tablets in healthy volunteers; 2 is B group, and embodiment 7 makesAverage blood concentration-the time graph of praziquantel composition in-stomach floating type sustained-release sheet.
Detailed description of the invention
The invention discloses a kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof. AbilityField technique personnel can be with reference to this paper content, obtains this praziquantel composition in-stomach floating type sustained-release sheet, spyNot it is pointed out that all similar replacements and changing is apparent for a person skilled in the art, they are all deemed to be included in the present invention. Preparation method of the present invention and application are by betterEmbodiment be described, related personnel obviously can be not departing from content of the present invention, spirit and scopeThis paper preparation method and application are changed or suitably changed and combination, realize and apply skill of the present inventionArt.
Used in a kind of praziquantel composition in-stomach floating type sustained-release sheet provided by the invention and preparation method thereofTo reagent and raw material all can be buied by market.
In order to make those skilled in the art can understand better technical scheme of the present invention, belowIn conjunction with the embodiments, further set forth the present invention:
The screening of embodiment 1 praziquantel composition in-stomach floating type sustained-release slice prescription
The present embodiment is to framework material in praziquantel composition in-stomach floating type sustained-release sheet provided by the inventionThe consumption of kind, consumption and bleach activator screens, wherein, and xanthans and hydroxypropyl methyl fiberElement has formed mixed matrix material, and 18 alcohol are bleach activator. Experimental design is specially: Three factors-levelsL9（33) orthogonal test, L9（33) orthogonal test factor be horizontally disposed with in table 1.
Table 1L9（33) orthogonal test factor and water-glass
Formula:
According to Three factors-levels L in table 19（33) orthogonal test, design 9 different praziquantel groupsCompound in-stomach floating type sustained-release slice prescription, each formula composition is in table 2.
The formula of table 2 praziquantel composition of the present invention in-stomach floating type sustained-release sheet
Preparation method:
According to the formula of table 2, get 60g HP-β-CD and be dissolved in 180g water, obtain quality percentageContent is 25% the HP-β-CD aqueous solution; Get 30g praziquantel, in 50 DEG C of stirrings 5 hours,4 DEG C refrigerate 16 hours, dry, and pulverize, and obtain praziquantel inclusion compound; Get gained praziquantel inclusion compound,45g praziquantel, according to the formula of table 2, get xanthans, hydroxypropyl methylcellulose, 18 alcohol, carbonAcid calcium, lactose, talcum powder, fully mix, and with the 80% ethanolic solution softwood processed of 60mL, crosses 18Mesh sieve is granulated, in 60 DEG C dry, whole grain, adds dolomol, after mixing, TDP single-punch tablet press is pressedSheet, pressure maintains 4～6kgcm-2. Tablet weight remains on 300mg left and right, diameter 10mm.
The performance evaluation of the praziquantel composition in-stomach floating type sustained-release sheet that different formulations makes:
Adopt study in vitro dissolution to test to investigate the praziquantel composition floating in stomach that the present embodiment makesThe performance of type sustained release tablets, concrete grammar is as follows:
Study in vitro dissolution experiment:
External flotation property is observed: get the praziquantel composition in-stomach floating type sustained-release sheet throwing that each formula makesEnter in 900mL simulated gastric fluid, temperature is 37 ± 0.5 DEG C, observes its flotation property, and tablet is at 30minInterior is floated and continue floating 10h is qualified products above. The results are shown in Table 3.
Drug release determination: get respectively the praziquantel composition in-stomach floating type sustained-release sheet 6 that each formula makesSheet, measures by dissolution method the second method, is specially: in stripping rotor, add dissolution medium500mL (pH=1.2), measures 37 ± 0.5 DEG C of temperature, rotating speed 100rmin-1, operation in accordance with the law, respectively at 1h,4h, 6h, 8h, 12h sampling 5mL(adds the simulated gastric fluid 5mL of preheating simultaneously), use immediately microporeMembrane filtration, gets subsequent filtrate and measures its absorbance at 263 ± 1mn place. This experiment adopts dissolution rate process 5The quality of individual sample point control tablet, i.e. 1h, 4h, 6h, 8h, the sample point that 12h is corresponding, wherein:1h accumulative total discharges to reach 10%～30%, 6 hours and reach 40%～60%, 12h and reaches more than 80%. AdoptWith evaluate formula: S=│ 20-1h │+│ 50-6h │+│ 90-12h │, to gained praziquantel compositionThe dissolution rate of in-stomach floating type sustained-release sheet is marked, and scoring reckling is excellent. The results are shown in Table 4.The external flotation property statistics of praziquantel composition in-stomach floating type sustained-release sheet that table 3 different formulations makes
The praziquantel composition in-stomach floating type sustained-release sheet dissolution rate testing result that table 4 different formulations makes
It is bright and clean slightly yellow that the praziquantel composition in-stomach floating type sustained-release sheet that each formula makes is outward appearanceSustained release tablets. The praziquantel composition floating in stomach that the known formula 6,7,8,9 of data makes from table 3Type sustained release tablets can be floating within 30min, and lasting meeting the requirements above for 10 hours of flotation time,Therefore formula 6,7,8, the 9 praziquantel composition in-stomach floating type sustained-release sheets that make are qualified products. From tableIn 4, data can draw, formula 9 is optimum formula, the quality hundred of mixed matrix material in this formulaPoint content be 30%(wherein hydroxypropyl methylcellulose account for 20%, xanthans accounts for 10%), 18 alcohol account for5%。
Flavouring agent screening:
Because medicine all has certain smell, cause, in the time of animals administer, being not easy by animals received,Especially the animal that dog, cat etc. have a sharp sense of taste, in order to facilitate administration, the present invention investigates at praziquantel simultaneouslyIn composition in-stomach floating type sustained-release sheet, add the food calling effect of diverse fragrant flavour agent to animal. Concrete grammar asUnder:
Experiment arranges 6 kinds of different given the test agent, is labeled as respectively A-F, by percentage to the quality, and itsMiddle A-E has added respectively in 1% the corresponding praziquantel composition of formula 9 stomach of diverse fragrant flavour agentFloating slowly releasing sheet, F does not add in the corresponding praziquantel composition of formula 9 stomach of any flavouring agentFloating slowly releasing sheet. The flavouring agent that A-E adds corresponds to respectively: chicken perfume (or spice), the fresh perfume (or spice) of liver, 902 meatPerfume, 608 fish raw meat perfume (or spice), saccharin sodium, these flavouring agents are all purchased from Chengdu, Sichuan the earth biotechnology company.
The preparation method of the corresponding praziquantel composition of A-E in-stomach floating type sustained-release sheet is: according to table 2The consumption of middle formula 9 corresponding various components, gets 60g HP-β-CD and is dissolved in 180g water,The quality percentage composition HP-β-CD aqueous solution that is 25%; Get 30g praziquantel, in 50 DEG CStir 5 hours, 4 DEG C refrigerate 16 hours, dry, and pulverize, and obtain praziquantel inclusion compound; Get gained pyrroleQuinoline ketone inclusion compound, praziquantel 45g, xanthans 30g, hydroxypropyl methylcellulose 60g, 18 alcohol 15g,Calcium carbonate 18g, lactose 33.9g, talcum powder 6g, flavouring agent 3g, fully mixes, with 80% of 60mLEthanolic solution softwood processed, crosses 18 mesh sieves and granulates, in 60 DEG C dry, whole grain, adds dolomol 2.1g,After mixing, TDP single-punch tablet press compressing tablet, pressure maintains 4～6kgcm-2. Tablet weight remains on300mg left and right, diameter 10mm.
Experimental technique:
30 of Healthy Dogs (being provided by Sichuan Agricultural University parasite laboratory) are provided, and body weight is14～18kg. Given the test agent A-F is placed on respectively in different plates, and a pair of to each plate oneShould be labeled as A-F. Plate is placed on the ground, between plate at intervals (more than 30cm),The taste that prevents several flavouring agents is obscured. Afterwards dog is placed on to plate limit, sees that it is to diverse fragrant flavour agentReaction. When each experiment, only put an animal, be numbered (1,2,3 by animal character ... 30)To note down. According to the reacting record data of dog, test sample is initiatively licked with "+" and represented, rightTablet do not react or away from represent with "-". In order to ensure the accuracy of data, carry out three timesRepeat experiment. Represent the food calling effect of test sample to dog with grazing rate.
Grazing rate=lick quantity/30 × 100% of the dog of test sample.
Data are arranged to calculating by biometric method, draw final result. Experimental result is shown inTable 5.
The food calling effect of the different praziquantel composition of table 5A-F in-stomach floating type sustained-release sheet
| Given the test agent | A | B | C | D | E | F |
| The search for food quantity of dog | 9 | 26 | 10 | 9 | 10 | 3 |
| Grazing rate | 30.00% | 86.67% | 33.33% | 30.00% | 33.33% | 10.00% |
From table 5, data can be found out, with the F given the test agent comparison of not adding flavouring agent, other are testedSample has all produced certain food calling effect to dog, wherein, the most obvious with the food calling effect of the fresh perfume (or spice) of liver again.Experimental result shows, by percentage to the quality, in praziquantel composition in-stomach floating type sustained-release sheet, adds1% the fresh perfume (or spice) of liver has good food calling effect to dog. Therefore, can make initiatively food of animal by adding flavouring agentWith praziquantel composition in-stomach floating type sustained-release sheet, convenient drug administration, is more conducive to the popularization of praziquantel and makesWith.
The preparation of embodiment 2 praziquantel composition in-stomach floating type sustained-release sheets
Get 500g HP-β-CD and be dissolved in 1166.7g water, obtain quality percentage composition and be 30%The HP-β-CD aqueous solution; Get 260g praziquantel, stir after 3h in 50 DEG C, be placed in-4 DEG C coldHide 20h, dry at 60 DEG C, pulverize, obtain praziquantel inclusion compound; Get gained praziquantel inclusion compound, pyrrole(K4M buys the limited public affairs of brilliant pure biochemical technology share in Shanghai for quinoline ketone 390g, hydroxypropyl methylcelluloseDepartment) 400g, xanthans 500g, calcium carbonate 200g, lactose 400g, talcum powder 40g, fully mix,With 90% the ethanol water softwood processed of 538mL, select after 20 mesh sieve granulate, in 40 DEG CDry under condition, whole grain, adds 15g dolomol, after mixing, and TDP single-punch tablet press compressing tablet,Pressure maintains 4～6kgcm-2, compacting, obtains approximately 6500, to obtain final product. Every praziquantel combination of gainedThe weight of thing in-stomach floating type sustained-release sheet remains on 300mg left and right, diameter 10mm.
The preparation of embodiment 3 praziquantel composition in-stomach floating type sustained-release sheets
Get 550g HP-β-CD and be dissolved in 2200g water, obtain quality percentage composition and be 20% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 340g praziquantel, stir after 10h in 45 DEG C, be placed in 4 DEG C coldHide 18h, dry at 60 DEG C, pulverize, obtain praziquantel inclusion compound; Get gained praziquantel inclusion compound, pyrroleQuinoline ketone 510g, hydroxypropyl methylcellulose 500g, xanthans 400g, magnesium carbonate 80g, calcium carbonate 80g,Starch 200g, superfine silica gel powder 100g, fully mix, soft by 70% the ethanol water system of 1104mLMaterial, after selection 18 mesh sieve are granulated, dry under 60 DEG C of conditions, whole grain, adds 30g hardFatty acid magnesium, after mixing, TDP single-punch tablet press compressing tablet, pressure maintains 4～6kgcm-2, compacting,Obtain approximately 6500, to obtain final product. The weight of every praziquantel composition in-stomach floating type sustained-release sheet of gained keepsAt 300mg left and right, diameter 10mm.
The preparation of embodiment 4 praziquantel composition in-stomach floating type sustained-release sheets
Get 600g HP-β-CD and be dissolved in 1800g water, obtain quality percentage composition and be 25% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 300g praziquantel, after 55 DEG C are stirred 5h, be placed in 0 DEG C of refrigeration18h, dries at 60 DEG C, pulverizes, and obtains praziquantel inclusion compound; Get gained praziquantel inclusion compound, praziquantel450g, hydroxypropyl methylcellulose 600g, xanthans 300g, sodium acid carbonate 90g, dodecyl sulphateSodium 90g, dextrin 200g, pregelatinized starch 139g, superfine silica gel powder 30g, talcum powder 30g, fully mixedClose, with 80% ethanol water softwood processed of 1100mL, after selection 18 mesh sieve are granulated,Dry under 55 DEG C of conditions, whole grain, adds 21g dolomol, after mixing, and TDP one-shot compressing tabletMachine compressing tablet, pressure maintains 4～6kgcm-2, compacting, obtains approximately 6500, to obtain final product. Every pyrrole of gainedThe weight of quinoline one compositions in-stomach floating type sustained-release sheet remains on 300mg left and right, diameter 10mm.
The preparation of embodiment 5 praziquantel composition in-stomach floating type sustained-release sheets
Get 520g HP-β-CD and be dissolved in 1560g water, obtain quality percentage composition and be 25% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 260g praziquantel, stir after 10h in 50 DEG C, be placed in 4 DEG C coldHide 19h, dry at 60 DEG C, pulverize, obtain praziquantel inclusion compound; Get gained praziquantel inclusion compound, pyrroleQuinoline ketone 590g, hydroxypropyl methylcellulose 400g, xanthans 470g, 18 alcohol 100g, magnesium carbonate 80g,Calcium carbonate 80g, starch 100g, dextrin 50g, lactose 50g, talcum powder 30g, superfine silica gel powder 30g,APEO lauryl alcohol sodium sulfovinate 40g, fully mixes, with 70% the ethanol water of 560mLSoftwood processed, after selection 18 mesh sieve are granulated, dry under 60 DEG C of conditions, whole grain, adds 15gDolomol, after mixing, TDP single-punch tablet press compressing tablet, pressure maintains 4～6kgcm-2, pressSystem, obtains approximately 6500, to obtain final product. The weight of every praziquantel composition in-stomach floating type sustained-release sheet of gainedRemain on 300mg left and right, diameter 10mm.
The preparation of embodiment 6 praziquantel composition in-stomach floating type sustained-release sheets
Get 500g HP-β-CD and be dissolved in 1351.9g water, obtain quality percentage composition and be 27%The HP-β-CD aqueous solution; Get 340g praziquantel, after 50 DEG C are stirred 10h, be placed in-4 DEG CRefrigeration 16h, dries at 60 DEG C, pulverizes, and obtains praziquantel inclusion compound; Get gained praziquantel inclusion compound,Praziquantel 310g, hydroxypropyl methylcellulose 580g, xanthans 500g, 18 alcohol 200g, magnesium carbonate200g, starch 400g, talcum powder 40g, fully mix, by 80% the ethanol water system of 800mLSoftwood, after selection 18 mesh sieve are granulated, dry under 50 DEG C of conditions, whole grain, adds 10gDolomol, 20g microcrystalline cellulose, after mixing, TDP single-punch tablet press compressing tablet, pressure maintains4～6kg·cm-2, compacting, obtains approximately 6500, to obtain final product. Every praziquantel composition floating in stomach of gainedThe weight of type sustained release tablets remains on 300mg left and right, diameter 10mm.
The preparation of embodiment 7 praziquantel composition in-stomach floating type sustained-release sheets
Get 600g HP-β-CD and be dissolved in 1800g water, obtain quality percentage composition and be 25% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 300g praziquantel, after 50 DEG C are stirred 5h, be placed in 0 DEG C of refrigeration16h, dries at 60 DEG C, pulverizes, and obtains praziquantel inclusion compound; Get gained praziquantel inclusion compound, praziquantel450g, hydroxypropyl methylcellulose 600g, xanthans 300g, 18 alcohol 150g, calcium carbonate 180g,Lactose 339g, talcum powder 60g, fully mix, with 80% the ethanol water softwood processed of 800mL,Select after 18 mesh sieve granulate, dry under 50 DEG C of conditions, whole grain, adds 21g stearic acidMagnesium, after mixing, TDP single-punch tablet press compressing tablet, pressure maintains 4～6kgcm-2, compacting, obtainsMust approximately 6500, to obtain final product. The weight of every praziquantel composition in-stomach floating type sustained-release sheet of gained keepsAt 300mg left and right, diameter 10mm.
The preparation of embodiment 8 praziquantel composition in-stomach floating type sustained-release sheets
Get 500g HP-β-CD and be dissolved in 1500g water, obtain quality percentage composition and be 25% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 340g praziquantel, after 50 DEG C are stirred 5h, be placed in 0 DEG C of refrigeration18h, dries at 60 DEG C, pulverizes, and obtains praziquantel inclusion compound; Get gained praziquantel inclusion compound, praziquantel510g, hydroxypropyl methylcellulose 400g, xanthans 450g, 18 alcohol 100g, magnesium carbonate 160g,Starch 200g, talcum powder 40g, chicken essence 45g, fully mixes, with 80% the ethanol of 900mLAqueous solution softwood processed, after selection 18 mesh sieve are granulated, dry under 50 DEG C of conditions, whole grain,Add 15g microcrystalline cellulose, after mixing, TDP single-punch tablet press compressing tablet, pressure maintains4～6kg·cm-2, compacting, obtains approximately 6500, to obtain final product. Every praziquantel composition floating in stomach of gainedThe weight of type sustained release tablets remains on 300mg left and right, diameter 10mm.
The preparation of embodiment 9 praziquantel composition in-stomach floating type sustained-release sheets
Get 570g HP-β-CD and be dissolved in 1710g water, obtain quality percentage composition and be 25% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 260g praziquantel, after 50 DEG C are stirred 5h, be placed in 0 DEG C of refrigeration18h, dries at 60 DEG C, pulverizes, and obtains praziquantel inclusion compound; Get gained praziquantel inclusion compound, praziquantel390g, hydroxypropyl methylcellulose 550g, xanthans 500g, 18 alcohol 200g, magnesium carbonate 200g,Starch 200g, dextrin 200g, talcum powder 100g, the fresh fragrant 10g of liver, the fragrant 5g of 902 meat, fully mixes,With 80% the ethanol water softwood processed of 1000mL, select after 18 mesh sieve granulate, inDry under 50 DEG C of conditions, whole grain, adds 15g microcrystalline cellulose, 15g tricalcium phosphate, and after mixing,TDP single-punch tablet press compressing tablet, pressure maintains 4～6kgcm-2, compacting, obtains approximately 6500, to obtain final product.The weight of every praziquantel composition in-stomach floating type sustained-release sheet of gained remains on 300mg left and right, diameter10mm。
The preparation of embodiment 10 praziquantel composition in-stomach floating type sustained-release sheets
Get 600g HP-β-CD and be dissolved in 1800g water, obtain quality percentage composition and be 25% hydroxylThe third group-beta-cyclodextrin aqueous solution; Get 290g praziquantel, after 50 DEG C are stirred 8h, be placed in 2 DEG C of refrigerations18h, dries at 60 DEG C, pulverizes, and obtains praziquantel inclusion compound; Get gained praziquantel inclusion compound, praziquantel460g, hydroxypropyl methylcellulose 600g, xanthans 300g, 18 alcohol 150g, magnesium carbonate 60g, carbonAcid hydrogen sodium 60g, lauryl sodium sulfate 60g, lactose 339g, talcum powder 60g, the fresh fragrant 10g of liver, 608The fragrant 10g of fish raw meat, saccharin sodium 10g, fully mixes, with 85% the ethanol water softwood processed of 800mL,Select after 20 mesh sieve granulate, dry under 55 DEG C of conditions, whole grain, adds 21g crystallite fibreDimension, after mixing, TDP single-punch tablet press compressing tablet, pressure maintains 4～6kgcm-2, compacting, obtainsMust approximately 6500, to obtain final product. The weight of every praziquantel composition in-stomach floating type sustained-release sheet of gained remains on300mg left and right, diameter 10mm.
Embodiment 11 praziquantel composition in-stomach floating type sustained-release sheet release dynamics researchs
For release dynamics and the mechanism of research praziquantel composition in-stomach floating type sustained-release sheet, get embodiment76 of the praziquantel composition in-stomach floating type sustained-release sheets that make, survey according to dissolution method the second methodThe release of determining praziquantel composition in-stomach floating type sustained-release sheet, is specially: in stripping rotor, add strippingMedium 500mL (pH=1.2), measures 37 ± 0.5 DEG C of temperature, rotating speed 100rmin-1, operation in accordance with the law, pointNot in 1h, 4h, 6h, 8h, 12h sampling 5mL(adds the simulated gastric fluid 5mL of preheating simultaneously), verticalUse filtering with microporous membrane, get subsequent filtrate and measure its absorbance at 263 ± 1mn place, obtain drug release data.Drug release data is carried out to matching by following Mathematical Modeling:
Zeroth order equation:
Qt=K0·t
Wherein, QtThe dissolution rate of medicine at time t; K0It is constant rate of release.
First-order equation:
ln(100-Qt)=ln100-K1·t
Wherein, QtThe dissolution rate of medicine at time t; K1It is rate of release constant.
Higuchi equation:
Qt=KH·t1/2
Wherein, QtThe dissolution rate of medicine at time t; KHIt is rate of release constant.
Study in vitro dissolution experimental result:
The drug release data of the praziquantel composition in-stomach floating type sustained-release sheet that embodiment 7 is made is being countedAfter learning models fitting, find, the release of praziquantel composition in-stomach floating type sustained-release sheet provided by the invention is movingMechanics meets first-order equation, illustrates that praziquantel composition in-stomach floating type sustained-release sheet provided by the invention meetsOne-level release equations.
Investigating embodiment 2 to embodiment 6, embodiment 8 to embodiment 10 according to identical experimental technique makesThe release dynamics of the praziquantel composition in-stomach floating type sustained-release sheet obtaining, obtains similar experimental result,The praziquantel composition stomach that makes of the embodiment of the present invention 2 to embodiment 6, embodiment 8 to embodiment 10The release dynamics of interior floating slowly releasing sheet meets first-order equation, and praziquantel combination provided by the invention is describedThing in-stomach floating type sustained-release sheet meets one-level release equations.
Pharmacokinetic in embodiment 12 praziquantel composition in-stomach floating type sustained-release lamellar bodies
Get the praziquantel composition in-stomach floating type sustained-release sheet that embodiment 7 makes, using dog as subjects,Study pharmacokinetics in its body.
Dosage regimen and sample collection:
12 of Healthy Dogs (being provided by Sichuan Agricultural University parasite laboratory) are provided, and body weight is14～18kg, is divided into two groups of A, B at random, 6 every group. Dog is overnight fasting before taking medicine, praziquantel tabletsIn the praziquantel composition stomach that agent (buying in Anhui Dongsheng Pharmaceutical Co., Ltd) and embodiment 7 make, floatFloating type sustained release tablets dosage is 50mgkg-1. A group dog provides praziquantel tablets in healthy volunteers, B group dog to provide realExecute the praziquantel composition in-stomach floating type sustained-release sheet that example 7 makes. In experimentation, allow dog anyDrinking-water, food 8h after administration provides. A, B group take medicine after 0,0.5,1,2,3,4,5,Difference blood sampling 3.0mL when 6,8,10h, and in 3500rmin-1Centrifugal 10min, gets upper plasma,In-20 DEG C of preservations.
HPLC analysis condition and plasma sample processing:
Within 2011, on InternationalJournalofNanomedicine, send out according to people such as Pan Baoliang《SolidlipidnanoparticlesuspensionenhancedthetherapeuticefficacyofPraziquantelagainsttapeworm " the middle data of recording, correct obtains the present embodiment detection sideThe chromatographic condition of method: column temperature: 25 DEG C; Mobile phase: methyl alcohol: water=70:30 (v/v); Flow velocity: 1.0mLmin-1；Wavelength: 215nm. Plasma sample processing: get dog plasma 0.5mL in glass centrifuge tube, add in advanceThe volume ratio preparing is methyl-tertbutyl ether/carrene mixed solution 3mL of 2:1, and whirling motion mixes1min, puts into centrifuge 3500rmin-1Centrifugal 20min, by upper strata transfer to band fill in glass tube,Allow sample bone dry by the method vacuumizing (45 DEG C), then dissolve with 500 μ L mobile phases, at a high speed12000rmin in refrigerated centrifuge-1Centrifugal 5min, carries out HPLC detection after getting its supernatant liquid filtering.
The preparation of calibration curve:
Get 7 parts of each 1.0mL of blank plasma, adding respectively concentration is 0.10,0.20,0.50,1.00,2.00, 5.00，10.00μg·mL-1Praziquantel standard operation liquid 1.0mL, vortex makes to mix, by above-mentionedAfter plasma sample disposal methods, carry out HPLC analysis. Obtain calibration curve equation:y=27.26x-6.693（r2=0.9996）。
Method validation:
With 0.20,2.00,10.00 μ gmL-1The quality control of low middle Senior Three kind concentration Criterion curve,By above-mentioned HPLC analysis condition method operation. The average recovery rate of low middle Senior Three kind concentration is respectively 103.3± 5.5%, 96.0 ± 3.7%, 94.6 ± 3.3%(n=12); In a few days RSD is respectively 4.07%, 1.19%,3.20%(n=4); In the daytime RSD is respectively 6.52%, 3.53%, 2.60%(n=4). Show the partyMethod is applicable to the mensuration of biological sample.
Data statistical analysis method:
According to the sample HPLC analysis result of the different time points of collecting, bring calibration curve equation into:y=27.26x-6.693（r2=0.9996), can draw the pyrrole quinoline in the sample that each time point collectsThe concentration of ketone, the blood concentration of the praziquantel that this time point is corresponding. With blood concentration, the time is drawn to bloodConcentration-time graph, can directly obtain maximum plasma concentration (C according to time front of blood concentrationmax）With the time (T that reaches peak concentrationmax). Then, then calculate other parameters: eliminate speed (Ke），Half-life (t1/2），AUC0-t(trapezoidal method calculating).
Relative bioavailability (F%)=AUC0-∞(praziquantel composition in-stomach floating type sustained-release sheet)/AUC0-∞(praziquantel tablets in healthy volunteers) × 100%.
Experimental result:
Average blood concentration-the time graph of A group and B group is shown in Fig. 1, as can be seen from the figure, and praziquantelTablet has just reached Cmax at administration 1～2h, and floats in the praziquantel composition stomach that embodiment 7 makesFloating type sustained release tablets 4～6h after administration just reaches Cmax. And the praziquantel that embodiment 7 makes combinationThe time front of blood concentration of thing in-stomach floating type sustained-release sheet is more mild, and effective blood drug concentration is held timeLonger.
Draw according to above-mentioned data statistical analysis method the praziquantel group that praziquantel tablets in healthy volunteers and embodiment 7 makeThe pharmacokinetic parameter data of compound in-stomach floating type sustained-release sheet, in table 6.
The pharmacokinetic parameter of the different praziquantel formulations of table 6
Known according to data in table 6, compare praziquantel tablets in healthy volunteers, the praziquantel composition that embodiment 7 makesThe T of in-stomach floating type sustained-release sheetmaxAnd t1/2All significantly improve, significant difference, illustrates that embodiment 7 makesThe sustained release performance of praziquantel composition in-stomach floating type sustained-release sheet good. According to relative bioavailability meterCalculate formula and calculate the relatively biological of praziquantel composition in-stomach floating type sustained-release sheet that embodiment 7 makesAvailability is 140%, compares praziquantel tablets in healthy volunteers, in the praziquantel composition stomach that embodiment 7 makes, floatsThe bioavilability of floating type sustained release tablets has improved 40%. So, praziquantel composition stomach provided by the inventionThe time front of blood concentration of interior floating slowly releasing sheet is more mild, and the effective blood drug concentration time remains longer,Significantly improve the bioavilability of praziquantel.
Make according to identical Research on experimental methods embodiment 2 to embodiment 6, embodiment 8 to embodiment 10Pharmacokinetics in the body of the praziquantel composition in-stomach floating type sustained-release sheet obtaining, has obtained similar experimentAs a result, obtain the praziquantel composition stomach that embodiment 2 to embodiment 6, embodiment 8 to embodiment 10 makeThe time front of blood concentration of interior floating slowly releasing sheet is more mild, and bioavilability significantly improves. So,The time front of blood concentration of praziquantel composition in-stomach floating type sustained-release sheet provided by the invention is more flatSlow, the effective blood drug concentration time remains longer, has significantly improved the bioavilability of praziquantel.
Below be only the preferred embodiment of the present invention, it should be pointed out that above-mentioned preferred embodiment notShould be considered as limitation of the present invention, protection scope of the present invention should taking claim limited range asAccurate. For those skilled in the art, without departing from the spirit and scope of the present invention,Can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (4)
1. a praziquantel composition in-stomach floating type sustained-release sheet, is characterized in that, it comprises following weightThe supplementary material of part:
Described praziquantel composition in-stomach floating type sustained-release sheet prepares by the following method:
Step 1: the supplementary material of getting above-mentioned weight portion;
Step 2: get described HP-β-CD and mix with water, obtain the HP-β-CD aqueous solution;Get the described praziquantel of 30 weight portions and the described HP-β-CD aqueous solution through inclusion, dry,Pulverize, obtain the first product;
Step 3: get the described praziquantel of described the first product, surplus, described hydroxypropyl methyl fiberPlain, described xanthans, described 18 alcohol, described calcium carbonate, described lactose, mixed with described talcum powderClose, obtain the second product;
Step 4: get described the second product and mix with ethanol water, through softwood processed, granulate, dryAfter, mixing with described dolomol, compressing tablet, to obtain final product.
2. praziquantel composition in-stomach floating type sustained-release sheet according to claim 1, is characterized in that,Described supplementary material also comprises flavouring agent.
3. praziquantel composition in-stomach floating type sustained-release sheet according to claim 2, is characterized in that,Described flavouring agent be a kind of in chicken essence, the fresh perfume (or spice) of liver, 902 meat perfume (or spice), 608 fish raw meat perfume (or spice), saccharin sodium orBoth above mixtures.
4. a preparation method for praziquantel composition in-stomach floating type sustained-release sheet, is characterized in that, comprisesFollowing steps:
Step 1: the supplementary material of getting following weight portion:
Step 2: get described HP-β-CD and mix with water, obtain the HP-β-CD aqueous solution;Get the described praziquantel of 30 weight portions and the described HP-β-CD aqueous solution through inclusion, dry, pulverize,Obtain the first product;
Step 3: get the described praziquantel of described the first product, surplus, described hydroxypropyl methylcellulose,Described xanthans, described 18 alcohol, described calcium carbonate, described lactose, mix with described talcum powder,The second product;
Step 4: get described the second product and mix with ethanol water, through softwood processed, granulate, after being dried,Mix with described dolomol, compressing tablet, to obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410054176.5A CN103800297B (en) | 2014-02-18 | 2014-02-18 | A kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410054176.5A CN103800297B (en) | 2014-02-18 | 2014-02-18 | A kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103800297A CN103800297A (en) | 2014-05-21 |
| CN103800297B true CN103800297B (en) | 2016-05-11 |
Family
ID=50698003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410054176.5A Active CN103800297B (en) | 2014-02-18 | 2014-02-18 | A kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103800297B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106377504A (en) * | 2016-10-10 | 2017-02-08 | 朱隆娅 | Praziquantel premix and preparation method thereof |
| CN109432440B (en) * | 2018-11-30 | 2022-04-26 | 佛山科学技术学院 | Praziquantel hydroxypropyl cyclodextrin inclusion compound and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101468100A (en) * | 2007-12-29 | 2009-07-01 | 北京琥珀光华医药科技开发有限公司 | Method for preparing digitalis floating tablets and use thereof |
-
2014
- 2014-02-18 CN CN201410054176.5A patent/CN103800297B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101468100A (en) * | 2007-12-29 | 2009-07-01 | 北京琥珀光华医药科技开发有限公司 | Method for preparing digitalis floating tablets and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 吡喹酮-羟丙基-β-环糊精包合物的制备;冯桂芬等;《西北农业学报》;20071231;第16卷(第4期);摘要 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103800297A (en) | 2014-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69629797T2 (en) | CONTROLLED RELEASE OF MATERIALS MATRIX | |
| Malakar et al. | Use of response surface methodology in the formulation and optimization of bisoprolol fumarate matrix tablets for sustained drug release | |
| Huang et al. | A novel plug-controlled colon-specific pulsatile capsule with tablet of curcumin-loaded SMEDDS | |
| JPH09509184A (en) | Controlled release composition | |
| CN103800280A (en) | Fluvastatin sodium pharmaceutical composition | |
| CN105338970B (en) | Medicament capsule compound formulation comprising Tadalafei and Tamsulosin | |
| CN103237543A (en) | Capsule and powder formulations containing lanthanum compounds | |
| Kotagale et al. | Eudragit-S, Eudragit-L and cellulose acetate phthalate coated polysaccharide tablets for colonic targeted delivery of azathioprine | |
| CN103800297B (en) | A kind of praziquantel composition in-stomach floating type sustained-release sheet and preparation method thereof | |
| Zhang et al. | Preparation of a colon-specific sustained-release capsule with curcumin-loaded SMEDDS alginate beads | |
| Wang et al. | Formulation and evaluation of gastric-floating controlled release tablets of Ginkgolides | |
| CN102462675B (en) | A kind of Bezafibrate sustained release tablet and preparation method thereof | |
| CN106511348A (en) | Huperzine-A framework particles, orally disintegrating tablets and preparation methods thereof | |
| JP2021075686A (en) | Cellulose composition, tablet, and orally disintegrating tablet | |
| Pawar et al. | Formulation and evaluation of oral colon targeted tablet of budesonide | |
| CN103860495B (en) | Finasteride dispersible tablet and preparation method thereof | |
| US9358205B2 (en) | Modified starch derivative-based matrix for colon targeting | |
| Salve | Development and in vitro evaluation of gas generating floating tablets of metformin hydrochloride | |
| CN101703481B (en) | Ribavirin lipid microsphere effervescent granules | |
| CN1887312A (en) | Chinese medicine composition and its prepn process and quality control method | |
| CN110960501B (en) | Norfloxacin capsule and preparation method thereof | |
| CN107029240A (en) | Purposes of the dendritic macromole polyamide amine in rutaecarpin | |
| Deshmukh | Development and In-vitro evaluation of colon specific indomethacin matrix tablet for the treatment of inflammatory bowel disease | |
| Uwah et al. | Plants as pharmaceutical excipients in oral sustained drug delivery systems: a review | |
| CN108379235A (en) | It being capable of quickly disintegrated tacrolimus sustained-release tablet composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |