CN117695337A - Slow-release suspension of lignum sappan and preparation method thereof - Google Patents
Slow-release suspension of lignum sappan and preparation method thereof Download PDFInfo
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- CN117695337A CN117695337A CN202311755312.9A CN202311755312A CN117695337A CN 117695337 A CN117695337 A CN 117695337A CN 202311755312 A CN202311755312 A CN 202311755312A CN 117695337 A CN117695337 A CN 117695337A
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a lignum naucleae sustained-release suspension and a preparation method thereof. The invention prepares the lignum naucleae resin microcapsule by using an aqueous dispersion coating technology based on a fluidized bed coating method; uniformly dispersing the danshenmu resin microcapsules in a suspension matrix to obtain a danshenmu slow-release suspension. The preparation method has simple process and lower cost, replaces the traditional film coating process which adopts organic solvents such as acetone, ethanol and the like as mediums at present, can solve the problems of inflammability and explosiveness of the organic solvents, and is convenient for industrial production; after coating, the medicine is released slowly, so that the irritation to gastrointestinal tract is reduced, the acting time of the medicine is prolonged, and the administration times of patients are reduced. Compared with the common preparation, the sustained-release preparation is convenient to carry, reduces the administration frequency, is more suitable for children and dysphagia patients to take, and greatly improves the medication compliance of patients. Meanwhile, the medicine hardly undergoes ion exchange in the oral cavity, and the bitter taste of the medicine can be effectively covered.
Description
Technical Field
The invention belongs to the technical field of preparation of pharmaceutical preparations, and particularly relates to a lignum sappan sustained-release suspension and a preparation method thereof.
Background
The lignum Dalbergiae Odoriferae is also called lignum Santali albi, fel Ursi, xiong Danshu, etc., and is prepared from radix Rubiae family plant lignum Santali albiNaucLea officinaLisPierre, ex Pitard) dried stems and roots, harvested annually. The Ardisia japonica has the effects of clearing heat, detoxicating, detumescence and relieving pain, is always used as a folk medicinal plant, is mainly used as a medicine in stem parts (1977 edition pharmacopoeia), is used for treating cold and fever, acute pharyngitis, pneumonia and the like, is mainly distributed in Hainan, guangdong, guangxi, yunnan and other places in China, and is one of the important traditional Chinese medicines in Hainan. Modern pharmacological researches show that the nauclea officinalis has the effects of resisting virus, resisting bacteria, resisting inflammation, relieving fever, easing pain, regulating immunity and the like, and is called as a plant antibiotic. The currently marketed dan wood preparation comprises dan wood extract tablets, dan wood extract capsules, dan wood injection, dan wood extract syrup and the like, and is clinically used for treating diseases such as cold fever, viral influenza, acute pharyngitis, acute tonsillitis, acute conjunctivitis, upper respiratory tract infection and the like.
In order to overcome the problems of uncomfortable taste, dysphagia, difficult dosage division and the like of the solid preparation, and achieve the effects of reducing the administration times of children and enhancing the curative effect, the development of an oral liquid sustained-release preparation with a sustained-release effect and good curative effect is very important.
The oral sustained-release suspension has the advantages of sustained-release tablets or capsules, and has the following advantages:
(1) Is convenient for oral administration, is particularly suitable for dysphagia patients such as children and old people, and improves medication compliance;
(2) The fluidity is good, and the dosage is easy to be divided;
(3) After oral administration, the oral liquid has large distribution area in the gastrointestinal tract, quick absorption and high bioavailability, and the suspension particles are uniformly dispersed and have small local irritation to the gastrointestinal tract;
(4) The suspended particles are small, the effect of gastric emptying rate is little after oral administration, and the individual difference is small;
(5) Is suitable for medicines with large dosage;
(6) The slow release preparation is added with a flavoring agent and the like, so that bad smell can be covered, and palatability is improved.
At present, no biliary tree sustained-release suspension exists at home and abroad, and the preparation method of the biliary tree sustained-release suspension described by the invention can greatly fill the market blank and has extremely high clinical application value and market value.
Disclosure of Invention
The invention aims to solve the problem that the traditional conventional preparation has short drug effect maintaining time, reduce the times of taking medicines by patients, especially improve the medication compliance of children patients, and provides the lignum sappan sustained-release suspension capable of improving the medication palatability and compliance of patients, prolonging the action time of the medicines and maintaining the stable blood concentration and the preparation method thereof.
The invention provides a biliary tree slow-release suspension which is prepared from a biliary tree resin microcapsule and a suspension matrix, wherein the biliary tree resin microcapsule is prepared by a fluidized bed coating method after being immersed by a biliary tree resin compound, and the fluidized bed coating method relates to a coating liquid.
The 'danmu resin compound' is prepared by mixing and stirring danmu medicine solution and medicine carrying resin.
In the lignum naucleae resin compound, the mass ratio of the lignum naucleae extract powder to the resin is within the range of 2:1-1:3.
In the lignum naucleae resin microcapsule, the mass ratio of the lignum naucleae resin compound to the coating liquid is 1:2-1:3.
The suspension matrix comprises a suspending agent, pure water, a flavoring agent, a wetting agent and a preservative.
The lignum naucleae solution is prepared by completely dissolving the lignum naucleae extract powder in ethanol-water solution.
The drug-loaded resin is a strong acid cation exchange resin, and the strong acid cation exchange resin is amberlite IRP69.
The impregnant is PEG4000.
The coating liquid is ethyl cellulose water dispersion suspension.
The suspending agent is one or more of xanthan gum, povidone and hydroxypropyl methyl cellulose.
The flavoring agent is one or the combination of sucrose and strawberry essence.
The wetting agent is one or the combination of glycerin and propylene glycol.
The preservative is propyl p-hydroxybenzoate.
The preparation method of the lignum naucleae sustained-release suspension comprises the following steps:
(1) Mixing lignum et radix Arisaema cum bile extract powder with cation exchange resin in ethanol-water solution, and stirring to obtain medicinal resin composition;
(2) Treating the drug resin compound in the step (1) with an impregnant, drying and sieving to obtain an impregnated drug resin compound;
(3) Coating the impregnated drug resin compound in the step (2) by adopting coating liquid based on a fluidized bed coating technology to prepare a lignum naucleae resin microcapsule;
(4) And (3) mixing the lignum naucleae resin microcapsule in the step (3) with auxiliary materials and pure water to prepare the lignum naucleae slow-release suspension.
The mass ratio of the nauclea officinalis extract powder to the cation exchange resin in the step (1) is 2:1-1:3, preferably 1:1.
The preparation method of the drug-resin compound in the step (1) comprises the following steps: dissolving lignum naucleae extract powder in ethanol-water solution, adding ion exchange resin after dissolving completely, filtering when the drug concentration in the solution no longer changes with time, and oven drying to obtain the final product; the concentration of the biliary tree solution is 2-10 mg/mL; the temperature of the preparation process is 25-45 ℃.
The temperature of the impregnation in the step (2) is 50-60 ℃, preferably 60 ℃.
The coating liquid in the step (3) is ethyl cellulose water dispersion suspension; the mass ratio of the drug resin compound to the coating liquid is 1:2-1:3, preferably 1:2.
The air inlet amount of the fluidized bed in the fluidized bed coating method in the step (3) is 25-55 m 3 /h, preferably 40m 3 And/h, wherein the air inlet temperature is 35-60 ℃, preferably 50 ℃, and the atomization pressure of the coating liquid during atomization spraying is 0.2-0.35 MPa, preferably 0.25MPa.
Compared with the prior art, the invention has the following beneficial effects:
the invention is characterized in that a biliary tree resin compound is prepared firstly; treating with impregnant, and oven drying to obtain impregnated medicinal resin compound; preparing the lignum naucleae resin microcapsule by using a fluidized bed coating technology; and preparing a suspension matrix, and uniformly dispersing the danwood resin microcapsules in the suspension matrix to finally obtain the danwood slow-release suspension. The resin material can cover the bitter taste of the medicine, so that the patient can swallow the medicine more easily; the water-based coating technology based on the fluidized bed coating method is adopted to replace the traditional film coating technology which adopts organic solvents such as acetone, ethanol and the like as mediums at present, so that the problems that the organic solvents are inflammable and explosive, an independent explosion-proof workshop is required for production, the investment is large and the like can be solved, the coating operation is facilitated, the coating time is shortened, and the method has important significance for industrialization; after coating, the medicine is slowly released, the acting time of the medicine is prolonged, the irritation of the medicine to gastrointestinal tract is reduced, and the medicine taking times of patients are reduced. The invention takes the danwood as a model drug for the first time, adopts the ion exchange resin technology to prepare the drug resin compound, and combines the dipping technology and the coating technology to prepare the drug resin slow-release microcapsule with better slow-release effect. The medicine has almost no ion exchange in the oral cavity, can effectively mask the taste, is very friendly to dysphagia patients such as children and old people, and enriches the choices of children for medicine application to a certain extent.
Description of the embodiments
The invention discloses a lignum naucleae sustained-release suspension and a preparation method thereof. The following is a complete description of the technical solutions of embodiments of the present invention, and the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. The materials and reagents used in the practice of the invention are commercially available.
Example 1 preparation of a sustained-release suspension of lignum naucleae, this example includes the following adjuvants: 200mg of xanthan gum, 220mg of sucrose, 8mg of propyl p-hydroxybenzoate, 15mg of strawberry essence, 60mL of pure water and 40mg of propylene glycol.
Step (1): preparing a drug resin compound, mixing 5mg/mL of a lignum naucleae solution with AmberLitetIRP 69 cation exchange resin according to a mass ratio of 1:1, magnetically stirring at 37 ℃, reacting for 3 hours, standing after the reaction is finished, performing suction filtration, washing away unbound drugs on the surface by using pure water, drying at 55 ℃, and sieving for later use;
step (2): preparing impregnated drug-loaded resin, weighing 3g of PEG4000, adding pure water, heating to 60 ℃ to dissolve the PEG4000, adding the drug-loaded resin compound prepared in the step (1), uniformly stirring, standing, carrying out suction filtration, drying at 55 ℃, and sieving for later use;
step (3): preparing coated microcapsule, taking the impregnated drug-loaded resin prepared in the step (2), placing the impregnated drug-loaded resin on a fluidized bed, and introducing air into the fluidized bed with the air inlet volume of 40m 3 And (h) allowing the material of the impregnated drug-carrying resin to be in a fluidized state at the air inlet temperature of 50 ℃, atomizing and spraying the coating liquid of the ethyl cellulose water dispersion, wherein the atomization pressure is 0.25MPa when the coating liquid is atomized and sprayed, so that the coating liquid is coated on the surface of the impregnated drug-carrying resin to prepare the coating resin, and then drying and sieving the coating resin for later use;
step (4): preparing a suspension matrix, namely taking a container 1, measuring pure water, dissolving the prescription amount of sucrose in the pure water, stirring to form a solution, taking a container 2, adding the prescription amount of propylene glycol, heating to 55 ℃, adding the prescription amount of propyl parahydroxybenzoate, cooling after dissolving, adding the prescription amount of xanthan gum into the solution, completely dissolving, adding the solution in the container 2 into the container 1, and finally adding strawberry essence, mixing until uniform, thus forming the suspension matrix. Taking 5mL of suspension matrix, adding 150mg of lignum naucleae resin microcapsule, stirring uniformly, and filling into a brown bottle to obtain the lignum naucleae slow-release suspension.
Example 2, preparation of a sustained-release suspension of lignum naucleae, this example includes the following adjuvants: povidone 200mg, sucrose 220mg, propyl p-hydroxybenzoate 8mg, strawberry essence 15mg, pure water 60mL and propylene glycol 40mg.
Step (1): preparing a drug resin compound, mixing 5mg/mL of a lignum naucleae solution with AmberLitetIRP 69 cation exchange resin according to a mass ratio of 1:1, magnetically stirring at 37 ℃, reacting for 3 hours, standing after the reaction is finished, performing suction filtration, washing away unbound drugs on the surface by using pure water, drying at 55 ℃, and sieving for later use;
step (2): preparing impregnated drug-loaded resin, weighing 3g of PEG4000, adding pure water, heating to 60 ℃ to dissolve the PEG4000, adding the drug-loaded resin compound prepared in the first step, uniformly stirring, standing, carrying out suction filtration, drying at 55 ℃, and sieving for later use;
step (3): preparing coated microcapsule, taking the impregnated drug-loaded resin prepared in the step (2), placing the impregnated drug-loaded resin on a fluidized bed, and introducing air into the fluidized bed with the air inlet volume of 40m 3 And (h) allowing the material of the impregnated drug-carrying resin to be in a fluidized state at the air inlet temperature of 50 ℃, atomizing and spraying the coating liquid of the ethyl cellulose water dispersion, wherein the atomization pressure is 0.25MPa when the coating liquid is atomized and sprayed, so that the coating liquid is coated on the surface of the impregnated drug-carrying resin to prepare the coating resin, and then drying and sieving the coating resin for later use;
step (4): preparing a suspension matrix, namely taking a container 1, measuring pure water, dissolving the prescription amount of sucrose in the pure water, stirring to form a solution, taking a container 2, adding the prescription amount of propylene glycol, heating to 55 ℃, adding the prescription amount of propyl parahydroxybenzoate, cooling after dissolving, adding the prescription amount of povidone into the solution, completely dissolving, adding the solution in the container 2 into the container 1, and finally adding strawberry essence, mixing until uniform, thus forming the suspension matrix. Taking 5mL of suspension matrix, adding 150mg of lignum naucleae resin microcapsule, stirring uniformly, and filling into a brown bottle to obtain the lignum naucleae slow-release suspension.
Example 3, preparation of a sustained-release suspension of lignum naucleae, this example includes the following adjuvants: 200mg of hydroxypropyl methylcellulose, 220mg of sucrose, 8mg of propyl p-hydroxybenzoate, 15mg of strawberry essence, 60mL of pure water and 40mg of propylene glycol.
Step (1): preparing a drug resin compound, mixing 5mg/mL of a lignum naucleae solution with AmberLitetIRP 69 cation exchange resin according to a mass ratio of 1:1, magnetically stirring at 37 ℃, reacting for 3 hours, standing after the reaction is finished, performing suction filtration, washing away unbound drugs on the surface by using pure water, drying at 55 ℃, and sieving for later use;
step (2): preparing impregnated drug-loaded resin, weighing 3g of PEG4000, adding pure water, heating to 60 ℃ to dissolve the PEG4000, adding the drug-loaded resin compound prepared in the first step, uniformly stirring, standing, carrying out suction filtration, drying at 55 ℃, and sieving for later use;
step (3): preparing coated microcapsule, taking the impregnated drug-loaded resin prepared in the step (2), placing the impregnated drug-loaded resin on a fluidized bed, and introducing air into the fluidized bed with the air inlet volume of 40m 3 And (h) allowing the material of the impregnated drug-carrying resin to be in a fluidized state at the air inlet temperature of 50 ℃, atomizing and spraying the coating liquid of the ethyl cellulose water dispersion, wherein the atomization pressure is 0.25MPa when the coating liquid is atomized and sprayed, so that the coating liquid is coated on the surface of the impregnated drug-carrying resin to prepare the coating resin, and then drying and sieving the coating resin for later use;
step (4): preparing a suspension matrix, namely taking a container 1, measuring pure water, dissolving the prescription amount of sucrose in the pure water, stirring to form a solution, taking a container 2, adding the prescription amount of propylene glycol, heating to 55 ℃, adding the prescription amount of propyl parahydroxybenzoate, cooling after dissolving, adding the prescription amount of hydroxypropyl methylcellulose into the solution, completely dissolving, adding the solution in the container 2 into the container 1, and finally adding strawberry essence, mixing until uniform, thus forming the suspension matrix. Taking 5mL of suspension matrix, adding 150mg of danmu resin microcapsule, stirring, and filling into a brown bottle after stirring uniformly, thus obtaining the danmu slow-release suspension.
Example 4 preparation of a sustained-release suspension of lignum naucleae, this example includes the following adjuvants: 200mg of xanthan gum, 220mg of sucrose, 8mg of propyl p-hydroxybenzoate, 15mg of strawberry essence, 80mL of pure water, 0.2g of glycerol and 0.6g of propylene glycol.
Step (1): preparing a drug resin compound, adding 10mg/mL of a lignum naucleae solution into AmberLiteIRP69 cation exchange resin according to a ratio of 1:1, magnetically stirring at 37 ℃, reacting for 3 hours, standing after the reaction is finished, filtering, washing away the unbound drugs on the surface by pure water, drying at 55 ℃, and sieving for later use;
step (2): preparing impregnated drug-loaded resin, weighing 1.5g of PEG4000, adding pure water, heating to 60 ℃ to dissolve the PEG4000, adding the drug-loaded resin compound prepared in the step one, uniformly stirring, standing, carrying out suction filtration, drying at 55 ℃, and sieving for later use;
step (3): preparing coated microcapsule, taking the impregnated drug-loaded resin prepared in the step (2), placing the impregnated drug-loaded resin on a fluidized bed, and introducing air into the fluidized bed with the air inlet volume of 40m 3 And (h) allowing the material of the impregnated drug-carrying resin to be in a fluidized state at the air inlet temperature of 50 ℃, atomizing and spraying the coating liquid of the ethyl cellulose water dispersion, wherein the atomization pressure is 0.25MPa when the coating liquid is atomized and sprayed, so that the coating liquid is coated on the surface of the impregnated drug-carrying resin to prepare the coating resin, and then drying and sieving the coating resin for later use;
step (4): preparing a suspension matrix, namely taking a container 1, measuring pure water, dissolving the prescription amount of sucrose in the pure water, stirring to form a solution, taking a container 2, adding the prescription amount of propylene glycol and glycerol, heating to 55 ℃, adding the prescription amount of propyl parahydroxybenzoate, cooling after dissolving, adding the prescription amount of xanthan gum into the solution, completely dissolving, adding the solution in the container 2 into the container 1, and finally adding strawberry essence, mixing until uniform, thus forming the suspension matrix. Taking 5mL of suspension matrix, adding 150mg of danmu resin microcapsule, stirring uniformly, and filling into a brown bottle, thus obtaining the danmu slow-release suspension.
Example 5, this example includes the following adjuvants: 200mg of povidone, 220mg of sucrose, 8mg of propyl p-hydroxybenzoate, 15mg of strawberry essence, 80mL of pure water, 0.2g of glycerol and 0.6g of propylene glycol.
Step (1): preparing a drug resin compound, adding 10mg/mL of a lignum naucleae solution into AmberLiteIRP69 cation exchange resin according to a ratio of 1:1, magnetically stirring at 37 ℃, reacting for 3 hours, standing after the reaction is finished, filtering, washing away the unbound drugs on the surface by pure water, drying at 55 ℃, and sieving for later use;
step (2): preparing impregnated drug-loaded resin, weighing 1.5g of PEG4000, adding pure water, heating to 60 ℃ to dissolve the PEG4000, adding the drug-loaded resin compound prepared in the step one, uniformly stirring, standing, carrying out suction filtration, drying at 55 ℃, and sieving for later use;
step (3): preparing a coating microcapsule, namely placing the impregnated drug-loaded resin prepared in the step (2) on a fluidized bed, introducing air with the air inlet quantity of 40m < 3 >/h and the air inlet temperature of 50 ℃ to enable the impregnated drug-loaded resin material to be in a fluidized state, atomizing and spraying ethyl cellulose water dispersion coating liquid, wherein the atomization pressure during atomization and spraying of the coating liquid is 0.25MPa, enabling the coating liquid to be coated on the surface of the impregnated drug-loaded resin, preparing the coating resin, drying and sieving for later use;
step (4): preparing a suspension matrix, namely taking a container 1, measuring pure water, dissolving the prescription amount of sucrose in the pure water, stirring to form a solution, taking a container 2, adding the prescription amount of propylene glycol and glycerol, heating to 55 ℃, adding the prescription amount of propyl parahydroxybenzoate, cooling after dissolving, adding the prescription amount of povidone into the solution, completely dissolving, adding the solution in the container 2 into the container 1, and finally adding strawberry essence, mixing until uniform, thus forming the suspension matrix. Taking 5mL of suspension matrix, adding 150mg of danmu resin microcapsule, stirring uniformly, and filling into a brown bottle, thus obtaining the danmu slow-release suspension.
Example 6 preparation of a sustained-release suspension of Nauclea officinalis, comprising 200mg of hydroxypropyl methylcellulose, 220mg of sucrose, 8mg of propyl p-hydroxybenzoate, 15mg of strawberry essence, 80mL of pure water, 0.2g of glycerol and 0.6g of propylene glycol.
Step (1): preparing a drug resin compound, adding 10mg/mL of a lignum naucleae solution into AmberLiteIRP69 cation exchange resin according to a ratio of 1:1, magnetically stirring at 37 ℃, reacting for 3 hours, standing after the reaction is finished, filtering, washing away the unbound drugs on the surface by pure water, drying at 55 ℃, and sieving for later use;
step (2): preparing impregnated drug-loaded resin, weighing prescribed amount of PEG4000, adding pure water, heating to 60 ℃ to dissolve the PEG4000, adding the drug-loaded resin compound prepared in the first step, uniformly stirring, standing, suction-filtering, and drying at 55 ℃ for later use;
step (3): preparing coated microcapsule, taking the impregnated drug-loaded resin prepared in the step (2), placing the impregnated drug-loaded resin on a fluidized bed, and introducing air into the fluidized bed with the air inlet volume of 40m 3 And (h) allowing the material of the impregnated drug-carrying resin to be in a fluidized state at the air inlet temperature of 50 ℃, atomizing and spraying the coating liquid of the ethyl cellulose water dispersion, wherein the atomization pressure is 0.25MPa when the coating liquid is atomized and sprayed, so that the coating liquid is coated on the surface of the impregnated drug-carrying resin to prepare the coating resin, and then drying and sieving the coating resin for later use;
step (4): preparing a suspension matrix, namely taking a container 1, measuring pure water, dissolving the prescription amount of sucrose in the pure water, stirring to form a solution, taking a container 2, adding the prescription amount of glycerin, heating to 55 ℃, adding the prescription amount of propyl parahydroxybenzoate, cooling after dissolving, adding the prescription amount of hydroxypropyl methylcellulose into the solution, completely dissolving, adding the solution in the container 2 into the container 1, and finally adding the strawberry essence, mixing until uniform, thus forming the suspension matrix. Taking 5mL of suspension matrix, adding 150mg of danmu resin microcapsule, stirring uniformly, and filling into a brown bottle, thus obtaining the danmu slow-release suspension.
Example 7, evaluation of the sedimentation volume ratio and redispersibility and mouthfeel of the biliary tree sustained-release suspension.
This example shows the results of evaluating the sedimentation volume ratio and redispersibility of the sustained-release suspension of biliary tree prepared in the previous examples, as shown in Table 1. The operation method of the sedimentation volume ratio is as follows: slowly releasing and mixing lignum et radix NaucleaeThe suspensions were placed in 50mL stoppered cylinders, respectively, and the height of the suspension at this time was recorded (H 0 ) The mixture was allowed to stand at 25℃for 3 hours, the height (H) was recorded, and the sedimentation volume ratio (F) was calculated. Redispersibility (RI) evaluation method: placing the suspension in the sedimentation volume ratio for 3h into a centrifuge tube, centrifuging at normal temperature in a high-speed refrigerated centrifuge for 10min at the rotating speed of 600r/min, taking out, turning over and shaking, and recording the required turning over times when the suspension is uniformly dispersed again. The results were evaluated for good, general, and poor grades (of which no more than 12 times were "good", 12 to 60 times were "good", more than 60 times were "general" and even dispersion was "poor"). Taste evaluation: the method is carried out by adopting a traditional subjective evaluation method.
TABLE 1 evaluation of the sedimentation volume ratio and redispersibility of the Nauclea officinalis sustained-release suspensions
As is clear from Table 1, the prepared slow-release suspension of Armillariella mellea had a volume ratio of more than 0.90 by volume ratio sedimentation and redispersibility evaluation, and the result of the redispersibility evaluation was good.
Example 8 in vitro release experiments of a sustained release suspension of danwood.
In vitro experiments are important for control and quality control, and mainly take dissolution rate as an index for investigation. In the embodiment, the biliary tree sustained-release suspension prepared in the embodiment 4 is taken as a solution to be tested, and the in-vitro release condition is examined by carrying out experiments for 3 times. 900mL of degassed 0.15mol/L NaCl was used as release medium; the rotation speed is 50r/min, and the temperature is 37+/-0.5 ℃. According to the method of pulp in the dissolution measurement of the 2020 edition of Chinese pharmacopoeia, 5ml of solution is respectively sucked from a dissolution instrument in 0.5, 1, 2, 4, 6, 8 and 12 hours, filtered by a microporous filter membrane with 0.22mm, the subsequent filtrate is taken for standby, corresponding medium with the same temperature and the same volume is timely added, the subsequent filtrate is sucked into HPLC, the peak area is recorded, and the concentration of each time point is calculated, so that the relation between the accumulated release amount and the time is investigated. The results are shown in Table 2.
Table 2 cumulative release of the biliary tree sustained-release suspension at different time points.
As shown in Table 2, the average cumulative release rate of the prepared biliary tree sustained-release suspension in vitro for 12 hours reaches 81.68%. Therefore, the prepared lignum naucleae sustained-release suspension meets the release requirement of sustained-release preparation, and the medicine can be slowly released into the body.
Example 9 stability experiments of a sustained-release suspension of danwood.
In this example, the stability of the sustained-release suspension of biliary tree prepared in each of the previous examples of the present invention was evaluated under conditions of exposure to high temperature, high humidity, light and air (specifically, as shown in table 3 below). The test was performed according to the relevant methods in the chinese pharmacopoeia version 2020. The content, in vitro release and the like are used as indexes. The stability of each suspension was evaluated. The results are shown in Table 4.
As is clear from Table 4, the content of the drug in the sustained-release suspension of Ardisia cochinchinensis under the conditions of high temperature, high humidity, light irradiation and air exposure was 96% or more, the related substances were not significantly changed, and the dissolution rate f of the drug was not significantly changed 2 Greater than 55 (respectively)
Proceeding f with the first day Release Curve 2 Factor evaluation, f 2 >55 illustrates that the two release curves are similar); therefore, the prepared danwood slow-release suspension has better stability.
TABLE 3 stability test conditions for the sustained-release suspension of Arisaema cum bile
TABLE 4 stability test results of the sustained-release suspension of Arisaema cum bile
In conclusion, the lignum sappan sustained-release suspension prepared by the invention has a good sustained-release effect, and the dissolution and stability of the suspension meet the sustained-release suspension standard, and the effective blood concentration can be provided after the preparation is taken for 1 time per day. Compared with the traditional medicinal preparation, the invention has obvious treatment effect, improves the medication compliance and palatability of patients, and simultaneously increases the selection of children medication.
While the embodiments of the present invention have been shown and described, it will be understood that the embodiments described above are illustrative and not restrictive, and that changes, modifications and substitutions may be made therein by those having ordinary skill in the art without departing from the scope of the present invention.
Claims (12)
1. The biliary tree sustained-release suspension is characterized by comprising the following preparation raw materials: the preparation comprises lignum naucleae extract powder, cation exchange resin, impregnant, coating material and other pharmaceutical excipients.
2. The sustained-release suspension of nauclea officinalis of claim 1, wherein the cation exchange resin is a strongly acidic cation exchange resin; the strong acid cation exchange resin is amberlite IRP69.
3. The sustained-release suspension of biliary tree according to claim 1, wherein the impregnating solution is PEG4000.
4. The sustained-release suspension of biliary tree according to claim 1, wherein the coating material is an aqueous ethylcellulose dispersion suspension.
5. The preparation method of the biliary tree sustained-release suspension is characterized by comprising the following steps:
(1) Mixing lignum et radix Arisaema cum bile extract powder with cation exchange resin in ethanol-water to obtain drug-loaded resin compound;
(2) Impregnating the drug resin compound obtained in the step (1) with an impregnating agent, stirring, drying and sieving to obtain impregnated drug-carrying resin;
(3) Coating the impregnated drug-carrying resin obtained in the step (2) and a coating material by adopting a fluidized bed coating method to obtain a lignum naucleae resin microcapsule;
(4) Mixing the lignum naucleae resin microcapsule obtained in the step (3) with pharmaceutical excipients and water to obtain the lignum naucleae slow-release suspension.
6. The preparation method of claim 5, wherein the mass ratio of the nauclea officinalis extract powder to the cation exchange resin in the step (1) is 2:1-1:3.
7. The method of claim 5, wherein the method of preparing the pharmaceutical resin composite in step (1) comprises: mixing the lignum naucleae extract powder with ethanol-water, adding ion exchange resin, filtering after the reaction is finished and drying at 50-60 ℃.
8. The method according to claim 5, wherein the method for preparing the lignum naucleae resin microcapsule in step (3) comprises the following steps: and (3) placing the impregnated drug-loaded resin prepared in the step (2) on a fluidized bed, carrying out air inlet to enable the impregnated drug-loaded resin material to be in a fluidized state, atomizing and spraying coating liquid of an ethyl cellulose water dispersion, enabling the coating liquid to be coated on the surface of the impregnated drug-loaded resin, preparing the coating resin, drying, and sieving for later use.
9. The method for preparing the lignum naucleae resin microcapsule according to claim 8, wherein the air inlet of the fluidized bed is 40m 3 And/h, the air inlet temperature is 50 ℃, and the atomization pressure is 0.25MPa when the coating liquid is atomized and sprayed; the mass ratio of the drug resin compound to the coating liquid is 1:2-1:3.
10. The method of claim 5, wherein the method of preparing the sustained-release suspension of nakedflower wood in step (4) comprises: firstly, preparing a suspension matrix, weighing according to the dosage, adding the required dosage of the danwood resin microcapsule, uniformly stirring, and then filling the mixture into a brown bottle, thus finishing the preparation of the danwood slow-release suspension.
11. The method for preparing a sustained-release suspension of nauclea officinalis as defined in claim 10, wherein the suspension matrix comprises suspending agent, pure water, flavoring agent, wetting agent, and antiseptic. Wherein the suspending agent is one or more of xanthan gum, povidone and hydroxypropyl methylcellulose; the flavoring agent is one or the combination of sucrose or strawberry essence; the wetting agent is one or two of glycerol and propylene glycol; the preservative is propyl p-hydroxybenzoate.
12. The method for preparing the biliary tree sustained-release suspension according to claim 10, wherein the suspension matrix is prepared by the following steps: taking a container 1, measuring pure water, dissolving a flavoring agent in the pure water, stirring to form a solution, taking a container 2, adding a wetting agent, heating to 55 ℃, adding a preservative, cooling after dissolution, adding a suspending agent into the solution, adding the solution in the container 2 into the container 1 after complete dissolution, and finally mixing until uniform to form a suspension matrix.
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