CN101658677A - Lovastatin-sulfobutyl ether-beta-cyclodextrin inclusion compound, preparation and preparation method thereof - Google Patents
Lovastatin-sulfobutyl ether-beta-cyclodextrin inclusion compound, preparation and preparation method thereof Download PDFInfo
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- CN101658677A CN101658677A CN200910190808A CN200910190808A CN101658677A CN 101658677 A CN101658677 A CN 101658677A CN 200910190808 A CN200910190808 A CN 200910190808A CN 200910190808 A CN200910190808 A CN 200910190808A CN 101658677 A CN101658677 A CN 101658677A
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Abstract
The invention discloses a lovastatin-sulfobutyl ether-beta-cyclodextrin inclusion compound, a preparation and a preparation method thereof. Sulfobutyl ether-beta-cyclodextrin is mixed with lovastatinby using proper water for injection to produce a cyclodextrin solution, wherein the weight of the sulfobutyl ether-beta-cyclodextrin is 1-100 times larger than that of the lovastatin; the lovastatin is dissolved into 25%-95% ethanol to produce a solution; the sulfobutyl ether-beta-cyclodextrin solution is mixed with the lovastatin ethanol solution for inclusion and for vacuum drying/freeze drying/spray drying to produce a crystallized lump lovastatin-cyclodextrin inclusion compound, and further to produce various preparations. By the employ of the invention, such problems as the low dissolution rate and small dissolution velocity of the lovastatin are solved; in addition, the invention has the advantages of good water solubility, strong stability, and good curative effect as well as fewerside effects.
Description
Technical field
The present invention relates to medical technical field, definite saying so utilized sulfobutyl ether-beta-cyclodextrin and lovastatin to form clathrate or improved dissolubility, the stability of lovastatin in water by the adding sulfobutyl ether-beta-cyclodextrin, makes sulfobutyl ether-beta-cyclodextrin inclusion compound and preparation thereby reduce side effect.
Background technology
Lovastatin has remarkable lipid-lowering effect, and extensive use treatment primary hypercholesterolemia, Secondary cases hypercholesterolemia prevent coronary heart disease to take place clinically, prevents sacculus plasty (PTCA) back restenosis in the percutaneous coronary artery angiography.Its mechanism of action is 1. to suppress the undue growth of newborn endothelium after the blood vessel endothelium breakage; 2. the migration and the propagation that suppress smooth muscle cell.The side effect of lovastatin has two aspects, and the first, owing to hydroxyl first valeric acid is suppressed the influence that produces.The metabolic end product of hydroxyl first valeric acid mainly is a cholesterol, the pure and mild ubiquinone of many mushrooms.Can reduce evidence of coronary heart diseases and mortality rate, and can make the atherosclerosis that has formed pull piece development to slow down, even go down, thereby provide new approach for the mankind prevent and treat coronary heart disease.
Up to the present, the lovastatin dosage form of having gone on the market is based on tablet and capsule.In recent years, along with lovastatin use increasingly extensive, have some new dosage forms to occur again.The lovastatin durative action preparation that Merck ﹠ Co., Inc. develops, it has used patent SCOT (one pack system osmotic membrane) technology of company, 24 hours blood drug level that can keep relative stability.The domestic ordinary tablet of also developing lovastatin, principal item has Luo Huaning, lovastatin, Teroltrat, slow releasing tablet, the capsule etc. in addition of other listings, common in the medication process have a gastrointestinal reaction: abdominal pain diarrhea, constipation, headache, insomnia, idol can cause that blood ammonia based transferase reversibility raises.
Summary of the invention
The method that the purpose of this invention is to provide a kind of lovastatin sulfobutyl ether-beta-cyclodextrin inclusion compound and preparation thereof.
The clathrate that the present invention proposes contains sulfobutyl ether-beta-cyclodextrin and lovastatin, both weight ratios are 1-100: 1, preferred weight ratio is 1-50: 1, preferred weight ratio is 1-25: 1,1-12: 1,1-6: 3 or 1-3: 1, described sulfobutyl ether-beta-cyclodextrin has 1,4,7 average substitution degree respectively.
The method for preparing described Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate may further comprise the steps:
(1) be 1-100 in sulfobutyl ether-beta-cyclodextrin and lovastatin weight ratio: 1 ratio is got raw material, and it is dissolved in respectively in aqueous systems or the organic solvent-aqueous systems.Selected suitable solvent has: water, methanol, ethanol, propanol, acetone, toluene, ethylene glycol, glycerol, isopropyl alcohol or the like, or its mixture; Preferred solvent is an alcoholic solution, and the ethanol of electing 25%-95% as is more arranged.
(2) two of blend step kinds of solution carry out enclose, and its inclusion method can adopt any of solvent method, polishing, spray drying method, ultrasonic method, preferred ultrasonic method.The inclusion reaction time is 5 minutes to 36 hours, and the preferred time is 1 hour; 10 ℃-80 ℃ of reaction temperatures, preferred temperature is 25 ℃-65 ℃
The present invention further proposes described Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate preferred manufacturing procedure and may further comprise the steps:
(1) be 1-25 in sulfobutyl ether-beta-cyclodextrin and lovastatin weight ratio: 1 ratio is got raw material, and lovastatin is dissolved in the 25%-95% ethanol;
(2) sulfobutyl ether-beta-cyclodextrin is dissolved in the distilled water;
(3) two kinds of solution of blend step (1) and step (2) carry out ultrasonic enclose, and the inclusion reaction time is 1 hour; Reaction temperature is 25 ℃-65 ℃.
Method of the present invention causes being formed on and has the deliquescent lovastatin sulfobutyl ether-beta-cyclodextrin inclusion compound of obvious improvement (or clathrate) in the water.Therefore the dissolubility of improving makes lovastatin easier being absorbed to patient's administration the time, thereby causes more effectively lovastatin physiological effect.
It constantly enlarges in the application of aspects such as medicine, food, agricultural, cosmetics, weaving cyclodextrin (cyclodextrin is called for short CD) at present.Common CD has α-CD, β-CD, γ-CD.Wherein, the intracavity diameter of α-CD has only 47nm～53nm, and is bad to the clathration of general medicine, and the present price comparison height of γ-CD has also limited its application.At present, in pharmaceutics extensive use be β-CD and derivant thereof.But the β-CD of unmodified can not satisfy the pharmaceutics application requirements in character aspect dissolubility, toxicity and the hemolytic, and after 1970, research emphasis has turned to the development and application of β-CDYan Shengwu.Wherein sulfobutyl ether-beta-cyclodextrin is exactly a kind of sulfonic group derivant of β CD, has that nephrotoxicity is little, an advantage such as good water solubility, haemolysis are little.In pharmaceutics, be mainly used in aspects such as increasing drug solubility, increase medicine stability and raising medicine biological activity.As shown in the table:
| Sample | Dissolubility (μ g/mL) |
| Lovastatin | ??2.14 |
| Lovastatin-Benexate Hydrochloride | ??28.46 |
| The lovastatin sulfobutyl ether-beta-cyclodextrin inclusion compound | ??57.32 |
As can be seen from the above table, lovastatin made lovastatin-Benexate Hydrochloride after, its dissolubility in aqueous solution is brought up to 28.46 μ g/mL, has improved about 13.3 times.After lovastatin made the lovastatin sulfobutyl ether-beta-cyclodextrin inclusion compound, its dissolubility in aqueous solution was brought up to 171.58 μ g/mL, has improved about 26.8 times (dissolubility of lovastatin crude drug in water is 2.14 μ g/mL).
The lovastatin Preparation methods of cyclodextrin inclusion complexes can adopt any in solvent method, polishing, spray drying method, the ultrasonic method etc. among the present invention.The preferred ultrasonic method that adopts of reaction.
Reaction preferably in Aquo System, is perhaps carried out in organic solvent-aqueous systems.Reaction is more preferably carried out in ethanol-water mixture.
In especially preferred experimental program, lovastatin is dissolved in the 25%-95% ethanol, sulfobutyl ether-beta-cyclodextrin is dissolved in the water, in any case alcoholic acid volume is unrestricted, as long as it is enough to dissolve lovastatin.Equally, in any case the volume of water is unrestricted, as long as it is enough to dissolve sulfobutyl ether-beta-cyclodextrin.
If the weight ratio of sulfobutyl ether-beta-cyclodextrin and lovastatin is lower than 1: 1 lower limit, the then not obvious increase of the dissolubility of lovastatin, if and it was greater than 100: 1, then excessive sulfobutyl ether-beta-cyclodextrin hinders the formation (dissolubility of lovastatin crude drug in water is 2.14 μ g/mL) of clathrate.As shown in the table:
| The weight ratio of sulfobutyl ether-beta-cyclodextrin and lovastatin | Dissolubility (μ g/mL) |
| ??1∶2 | ??7.08 |
| ??1∶1 | ??31.63 |
| ??50∶1 | ??31.85 |
| ??100∶1 | ??32.12 |
| ??110∶1 | ??26.26 |
Be apparent that when lovastatin mixed with sulfobutyl ether-beta-cyclodextrin with height ratio, the part lovastatin still kept not dissolving, in this case, undissolved chemical compound can be by filtering by removing in the reactant mixture.
In preferred embodiments, the response time is 5 minutes-36 hours.
In preferred embodiments, be reflected under about 10 ℃ of-80 ℃ of temperature and carry out, the temperature of carrying out inclusion reaction is not specifically limited, enough degree are at room temperature carried out in reaction, and the response time is generally-several hours a few minutes.
In especially preferred experimental program, carry out under 20 ℃ of-50 ℃ of temperature.
The microimaging figure of prepared Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate both had been different from the microimaging figure of lovastatin among the present invention, the microimaging figure that is different from sulfobutyl ether-beta-cyclodextrin again, also be different from the microimaging figure that lovastatin and sulfobutyl ether-beta-cyclodextrin get mixture, obviously visible lovastatin is the elongated tubular product such crystallization, sulfobutyl ether-beta-cyclodextrin is the amorphous crystallization, the both has in the physical mixture, and clathrate is the crystallization of tetragonal body shape.
The infrared spectrum of prepared Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate both had been different from the infrared spectrum of lovastatin among the present invention, the infrared spectrum that is different from sulfobutyl ether-beta-cyclodextrin again also is different from the infrared spectrum that lovastatin and sulfobutyl ether-beta-cyclodextrin get mixture.
The made Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate of the present invention can be prepared into various preparations, as various oral formulations (comprising tablet, granule, pill, mixture, drop pill, capsule etc.), injection (comprising injection, aseptic powder injection or freeze-dried powder and transfusion etc.).
Injection of the present invention is meant the clathrate and the water for injection of Lovastatin-sulfobutyl ether-beta-cyclodextrin.Wherein be as the criterion concentration for being respectively 5mg/ml with lovastatin content.
Freeze-dried powder of the present invention mainly is meant the inclusion complex in solution of Lovastatin-sulfobutyl ether-beta-cyclodextrin, suitable proppant/excipient, gets by lyophilization.Wherein be as the criterion with lovastatin content, specification is respectively two kinds of 5mg, 10mg.
Aseptic powder injection of the present invention mainly contains the clathrate of Lovastatin-sulfobutyl ether-beta-cyclodextrin, suitable proppant/excipient, and the powder that obtains by lyophilization/spray drying carries out aseptic subpackaged getting.Wherein be respectively two kinds of 5mg, 10mg with the lovastatin content specification that is as the criterion.
Transfusion of the present invention mainly contains the clathrate, water for injection of Lovastatin-sulfobutyl ether-beta-cyclodextrin, the instrumentality (reconciling thing as acceptable etc. oozing on sodium chloride, glucose and other pharmaceuticss) that oozes such as an amount of.Wherein be as the criterion concentration for being respectively 5mg/ml with lovastatin content.
The made enclose product of the present invention can mix with medicinal diluent, carrier or excipient, binding agent, lubricant, suspending agent, solubilizing agent, antioxidant, disintegrating agent (comprising their intermediary one or more mixture), makes various preparations.
Diluent of the present invention comprises ethanol, glycerol, water etc.
Carrier of the present invention or excipient comprise lactose, starch, glucose, methylcellulose, ethyl cellulose, mannitol, sorbose etc.
Binding agent of the present invention comprises hydroxypropyl cellulose, sodium carboxymethyl cellulose, ethanol, Polyethylene Glycol etc.
Lubricant of the present invention comprises enuatrol, sodium stearate, magnesium stearate, sodium acetate, micropowder silica gel etc.
Suspending agent of the present invention, solubilizing agent or antioxidant comprise nitrogen, carbon dioxide gas, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, disodiumedetate, cysteine etc.
Disintegrating agent of the present invention adopts polyvinylpyrrolidone, carboxymethyl starch sodium, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose etc.
Lovastatin enclose product of the present invention has the dissolubility of obvious improvement at aqueous phase, and stability improves greatly.Therefore, can more effective mode be delivered to patient's medicine-feeding part, have good effect, the advantage that toxic and side effects is low.
The specific embodiment
Embodiment 1: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 6g, lovastatin 1g, add the methanol solution of 75ml 35% and the distilled water of 25ml respectively, these two kinds of solution are mixed in the dissolving back fully, heating, temperature is under 25 ℃, stirred 30 minutes, and be cooled to room temperature, filter solution, the solution of gained carries out vacuum drying/lyophilization/spray drying, is Lovastatin-sulfobutyl ether-beta cyclodextrin clathrate.
Embodiment 2: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 3g, lovastatin 1g, add respectively and the alcoholic solution of 50ml 55% and the distilled water of 25ml, these two kinds of solution are mixed in the dissolving back fully, heating, temperature is under 45 ℃, stirred 1 hour, and be cooled to room temperature, filter solution, the solution of gained carries out vacuum drying/lyophilization/spray drying, is the Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 3: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 1g, lovastatin 1g, add the propanol solution of 25ml 75% and the distilled water of 25ml respectively, these two kinds of solution are mixed in the dissolving back fully, heating, temperature is under 65 ℃, stirred 90 minutes, and be cooled to room temperature, filter solution, the solution of gained carries out vacuum drying/lyophilization/spray drying, is the Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 4: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 1g, lovastatin 1g, add the acetone soln of % and the distilled water of 25ml respectively, these two kinds of solution are mixed in the dissolving back fully, heating, temperature is under 85 ℃, stirred 2 hours, and be cooled to room temperature, filter solution, the solution of gained carries out vacuum drying/lyophilization/spray drying, is the Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 5: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: press sulfobutyl ether-beta-cyclodextrin 5g, lovastatin 1g.In sulfobutyl ether-beta-cyclodextrin, the distilled water stirring and dissolving that adds 25ml, other gets the ethylene glycol solution dissolving that lovastatin adds 70ml 65%, mix in above-mentioned two kinds of solution, ultrasonic 30 minutes, with the membrane filtration of reuse 0.22 μ behind the membrane filtration of 0.45 μ, the solution of gained was after vacuum drying/lyophilization/spray drying, get white powder, i.e. Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 6: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 2g, lovastatin 1g.In sulfobutyl ether-beta-cyclodextrin, the distilled water stirring and dissolving that adds 25ml, other gets the toluene solution dissolving that lovastatin adds 35ml85%, mix in above-mentioned two kinds of solution, ultrasonic 1 hour, with the membrane filtration of reuse 0.22 μ behind the membrane filtration of 0.45 μ, the solution of gained was after vacuum drying/lyophilization/spray drying, get white powder, i.e. Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 7: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 4g, lovastatin 1g.In sulfobutyl ether-beta-cyclodextrin, the distilled water stirring and dissolving that adds 25ml, other gets lovastatin and adds the dissolving of 55ml80% aqueous isopropanol, mix in above-mentioned two kinds of solution, ultrasonic 90 minutes, with the membrane filtration of reuse 0.22 μ behind the membrane filtration of 0.45 μ, the solution of gained was after vacuum drying/lyophilization/spray drying, get white powder, promptly get the Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 8: the preparation of Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate: take by weighing sulfobutyl ether-beta-cyclodextrin 1g, lovastatin 1g.In sulfobutyl ether-beta-cyclodextrin, the distilled water stirring and dissolving that adds 25ml, other gets lovastatin and adds the dissolving of 20ml90% glycerol solution, mix in above-mentioned two kinds of solution, ultrasonic 2 hours, with the membrane filtration of reuse 0.22 μ behind the membrane filtration of 0.45 μ, the solution of gained was after vacuum drying/lyophilization/spray drying, get white powder, be the Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate.
Embodiment 9: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 315mg, amylum pregelatinisatum 100mg, mannitol 100mg, PVP powder 100mg, magnesium stearate 15mg, Pulvis Talci 200mg mix homogeneously, and controlling particle size is in 35 μ m-80 mu m ranges, the dry method direct compression, its principal agent lovastatin content is the 5mg/ sheet, promptly gets dispersible tablet of the present invention.
Embodiment 10: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 315mg, lactose 200mg, PEG6000 powder 20mg, sodium lauryl sulphate 30mg, magnesium stearate 5mg, sodium thiosulfate 63mg, carboxymethyl cellulose 30mg mix homogeneously, carry out tabletting by direct pressure closing, its principal agent lovastatin content is the 5mg/ sheet, promptly gets instant.
Embodiment 11: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 315mg, carboxymethyl starch sodium 60mg, polyvinylpyrrolidone 30mg, 75% ethanol 15ml mix homogeneously, encapsulated,, its principal agent lovastatin content is the 5mg/ grain, promptly gets capsule.
Embodiment 12: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 31.5g and be dissolved in the water for injection, 25g lactose and 2g0.1-0.2% active carbon, stirred 15-30 minute, behind the depyrogenation, filter decarburization, with the membrane filtration of 0.22 μ, after transferring to ormal weight with water for injection, gained solution is sub-packed in 1000 cillin bottles, carries out lyophilization, gets lovastatin clathrate freeze-dried powder.
Embodiment 13: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 31.5g and be dissolved in the water for injection, add 25g mannitol and 2g0.1-0.2% active carbon, stirred 15-30 minute, behind the depyrogenation, filter decarburization, with the membrane filtration of 0.22 μ, after transferring to ormal weight with water for injection then, gained solution carries out lyophilization, carries out aseptic subpackagedly in 1000 cillin bottles, and must cut down his spit of fland clathrate aseptic powder injection.
Embodiment 14: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 31.5g and be dissolved in the water for injection, add 10g sodium sulfite, 2g0.1-0.2% active carbon, stirred 15-30 minute, and regulated PH to 11 with sodium hydrate aqueous solution, behind the depyrogenation, filter decarburization, membrane filtration with 0.22 μ transfers to ormal weight with water for injection, and the packing of gained solution is made 1000 bottles, flowing steam sterilization 30 minutes must cut down his spit of fland clathrate injection.
Embodiment 15: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 31.5g and be dissolved in the water for injection, add 100g glucose for injection and 5g0.1-0.3% active carbon, stirred 15-30 minute, behind the depyrogenation, filter decarburization, with the membrane filtration of 0.22 μ, transfer to ormal weight with water for injection, gained solution is sub-packed in makes 1000 bottles in the infusion bottle, 115 ℃ of flowing steam sterilizations 30 minutes, lovastatin clathrate glucose injection.
Embodiment 16: get Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate 31.5g and be dissolved in the water for injection, add 1000g sodium chloride for injection and 5g0.1-0.3% active carbon, stirred 15-30 minute, behind the depyrogenation, filter decarburization, with the membrane filtration of 0.22 μ, transfer to ormal weight with water for injection, gained solution is sub-packed in makes 1000 bottles in the infusion bottle, 115 ℃ of flowing steam sterilizations 30 minutes, lovastatin clathrate sodium chloride injection.
Claims (8)
1. Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate, it is characterized in that: it contains sulfobutyl ether-beta-cyclodextrin and lovastatin, both weight ratios are 1-100: 1, and described sulfobutyl ether-beta-cyclodextrin has 1,4,7 average substitution degree respectively.
2. Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate according to claim 1 is characterized in that: the weight ratio of described sulfobutyl ether-beta-cyclodextrin and lovastatin is 1-50: 1.
3. Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate according to claim 1 is characterized in that: the weight ratio of described sulfobutyl ether-beta-cyclodextrin and lovastatin is 1-25: 1.
4. prepare the method for claim 1,2 or 3 described Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrates, it is characterized in that, said method comprising the steps of:
(1) gets raw material by the part by weight of sulfobutyl ether-beta-cyclodextrin and lovastatin, be dissolved in it in solvent respectively; Selected solvent is selected water, methanol, ethanol, propanol, acetone, toluene, ethylene glycol, glycerol, isopropyl alcohol for use, or their mixture;
(2) two kinds of solution obtaining of blend step (1) carry out enclose, and its inclusion method adopts any of solvent method, polishing, spray drying method, ultrasonic method; The inclusion reaction time is 5 minutes to 36 hours; 10 ℃-80 ℃ of reaction temperatures.
5, preparation method according to claim 4 is characterized in that: described solvent is the ethanol of 25%-95%.
6, preparation method according to claim 4 is characterized in that: described inclusion method uses ultrasonic method, and the described inclusion reaction time is 1 hour; Reaction temperature is 25 ℃-65 ℃.
7. the pharmaceutical preparation of adopting the described Lovastatin-sulfobutyl ether-beta-cyclodextrin clathrate of claim 1 to make, it is characterized in that: described pharmaceutical preparation is oral formulations or injection;
Wherein oral formulations comprises tablet, pill, granule, mixture, drop pill, capsule;
Injection comprises injection, freeze-dried powder, aseptic powder injection, transfusion;
In described pharmaceutical preparation, Lovastatin-sulfobutyl ether-beta-cyclodextrin is a principal agent, addition is a standard with two kinds of specifications of lovastatin content 5mg, 10mg in the preparation, and all the other are in medicinal diluent, carrier, binding agent, lubricant, suspending agent, solubilizing agent, antioxidant, disintegrating agent or the excipient one or more.
8, pharmaceutical preparation according to claim 7 is characterized in that:
Described medicinal diluent adopts one or more in ethanol, glycerol, the water;
Described carrier or excipient adopt one or more in lactose, starch, glucose, methylcellulose, ethyl cellulose, mannitol, the sorbose;
Described binding agent adopts one or more in hydroxypropyl cellulose, sodium carboxymethyl cellulose, ethanol, the Polyethylene Glycol;
Described lubricant adopts one or more in enuatrol, sodium stearate, magnesium stearate, sodium acetate, the micropowder silica gel;
Described suspending agent, solubilizing agent or antioxidant adopt one or more in nitrogen, carbon dioxide gas, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, disodiumedetate, the cysteine; Described disintegrating agent adopts one or more in polyvinylpyrrolidone, carboxymethyl starch sodium, cross linked polyvinyl pyrrolidone, the cross-linking sodium carboxymethyl cellulose.
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| CN105169407A (en) * | 2015-10-15 | 2015-12-23 | 重庆大学 | Sulfobutyl ether-beta-cyclodextrin inclusion compound of trimethoprim and powder injection preparation thereof |
| CN105194685A (en) * | 2015-10-15 | 2015-12-30 | 重庆大学 | Sulphaguanidine and sulfobutyl ether-beta-cyclodextrin inclusion compound and powder injection preparation |
| CN108813609A (en) * | 2018-06-22 | 2018-11-16 | 广东药科大学 | A kind of preparation method of grape seed extract sulfobutyl ether-beta-cyclodextrin inclusion compound |
| CN109771664A (en) * | 2019-01-30 | 2019-05-21 | 宁夏医科大学 | A kind of matrine-sulfobutyl ether beta-cyclodextrin composition and preparation method thereof |
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