技术领域technical field
本发明涉及一种丹皮酚纳米缓释制剂及其制备方法，属于丹皮酚纳米缓释制剂技术领域。The invention relates to a paeonol nano sustained-release preparation and a preparation method thereof, belonging to the technical field of paeonol nano sustained-release preparations.
背景技术Background technique
丹皮酚（paeonol）为常用中药牡丹皮、徐长卿等的主要有效成分，具有显著的镇痛、镇静、抗感染、抗氧化和抗肿瘤等作用，临床上用于治疗风湿病、牙痛、胃痛、皮肤病、高血压、心率失常等。由于丹皮酚具有易挥发、易氧化、水溶性差、生物半衰期短和对胃肠道黏膜有刺激性等缺点，影响其在制剂中的稳定性和体内生物利用度。改善这些缺陷，很多研究者致力于丹皮酚制剂的研究，如丹皮酚乳剂，丹皮酚-β环糊精包合物，丹皮酚微囊和丹皮酚纳米结构脂质载体等制剂。但由于这些制剂具有制备的粒径大，不可用于注射，制备工艺复杂，制备条件要求复杂和制备过程可能产生有毒有害物质等不足。Paeonol (paeonol) is the main active ingredient of commonly used traditional Chinese medicine Moutan Cortex, Xu Changqing, etc. It has significant analgesic, sedative, anti-infective, anti-oxidative and anti-tumor effects. It is clinically used to treat rheumatism, toothache, stomach pain, Skin diseases, high blood pressure, arrhythmia, etc. Paeonol has the disadvantages of being volatile, easily oxidized, poorly water-soluble, short biological half-life, and irritating to the gastrointestinal mucosa, which affect its stability in preparations and bioavailability in vivo. To improve these defects, many researchers are devoted to the study of paeonol preparations, such as paeonol emulsions, paeonol-β cyclodextrin inclusion complexes, paeonol microcapsules and paeonol nanostructured lipid carriers and other preparations. However, due to the large particle size of these preparations, they cannot be used for injection, the preparation process is complex, the preparation conditions are complicated, and the preparation process may produce toxic and harmful substances.
发明内容Contents of the invention
本发明正是针对现有技术存在的不足，提供一种具有粒径小、分散性强、稳定性好、缓慢释药、靶向性强等优点的丹皮酚纳米缓释制剂。The present invention aims at the deficiencies of the prior art, and provides a paeonol nano-sustained-release preparation with the advantages of small particle size, strong dispersibility, good stability, slow drug release, strong targeting and the like.
为解决上述问题，本发明所采取的技术方案如下：In order to solve the above problems, the technical scheme adopted in the present invention is as follows:
一种丹皮酚纳米缓释制剂，以聚氰基丙烯酸正丁酯为载体，通过油相滴入水相的界面自发缩聚法制备而成。A paeonol nano-sustained-release preparation is prepared by taking poly(n-butyl cyanoacrylate) as a carrier and interfacial spontaneous polycondensation method in which an oil phase is dropped into a water phase.
作为上述技术方案的进一步优化，本发明提供的一种丹皮酚纳米缓释制剂，通过以下过程制得：以聚氰基丙烯酸正丁酯为载药载体，在室温磁力搅拌条件下，将含有丹皮酚、乙酸乙酯、α-氰基丙烯酸正丁酯、丙酮的油相逐滴滴入由表面活性剂和超纯水混匀的酸性水相中，经过自发界面聚合，然后低温旋转蒸发除去丙酮，过滤，调pH值为中性，通过搅拌完全聚合获得乳白色混悬液或通过冷冻干燥获得冻干粉。所述的丙酮既为油相助溶剂也为丹皮酚的溶解剂，且油相溶剂为丙酮和乙酸乙酯。As a further optimization of the above-mentioned technical scheme, a paeonol nano-sustained-release preparation provided by the present invention is prepared through the following process: using n-butyl cyanoacrylate as a drug-loading carrier, under the condition of magnetic stirring at room temperature, will contain The oil phase of paeonol, ethyl acetate, n-butyl α-cyanoacrylate, and acetone is dropped dropwise into the acidic water phase mixed with surfactant and ultrapure water, undergoes spontaneous interfacial polymerization, and then low-temperature rotary evaporation Remove acetone, filter, adjust the pH value to be neutral, and obtain a milky white suspension through complete polymerization by stirring or freeze-dry to obtain a freeze-dried powder. The acetone is both an oil-phase co-solvent and a dissolving agent for paeonol, and the oil-phase solvent is acetone and ethyl acetate.
作为上述技术方案的进一步优化，所述表面活性剂为泊洛沙姆188和右旋糖苷-70的混合物。其中右旋糖苷-70也作为稳定剂。As a further optimization of the above technical solution, the surfactant is a mixture of poloxamer 188 and dextran-70. Among them, dextran-70 is also used as a stabilizer.
作为上述技术方案的进一步优化，本发明提供的一种丹皮酚纳米缓释制剂中，油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.04～0.10克，乙酸乙酯3.0～6.0毫升，α-氰基丙烯酸正丁酯0.15～0.35毫升；As a further optimization of the above technical solution, in the paeonol nano-sustained-release preparation provided by the present invention, the ratio of the oil phase raw materials is: 100 ml of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.04-0.10 g of paeonol , 3.0-6.0 ml of ethyl acetate, 0.15-0.35 ml of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.4～0.8克，右旋糖苷-70为0.6～1.1克；The raw material ratio of the water phase is: 100 ml of ultrapure water, 0.4-0.8 grams of poloxamer 188, and 0.6-1.1 grams of dextran-70;
进行自发界面聚合时的混合物pH值为1.5～3.5，磁力搅拌速率为750～950 r/min。The pH value of the mixture during spontaneous interfacial polymerization is 1.5-3.5, and the magnetic stirring speed is 750-950 r/min.
本发明与现有技术相比较，本发明的实施效果如下：The present invention compares with prior art, and implementation effect of the present invention is as follows:
本发明所述的一种丹皮酚纳米缓释制剂，形态为乳白色混悬液或白色冻干粉，形状为球形或椭球形，粒径小于200纳米，混悬液在超纯水中分散指数为0.128～0.213，电动势为-45.012～-30.102 mV；0.04%丹皮酚缓释制剂纳米囊包封率为63.182～77.6403%，载药量为28.241～41.253%，缓慢释药时间长达60小时。A paeonol nano-sustained-release preparation according to the present invention is in the form of milky white suspension or white freeze-dried powder, spherical or ellipsoidal in shape, with a particle diameter of less than 200 nanometers, and the dispersion index of the suspension in ultrapure water 0.128～0.213, the electromotive force is -45.012～-30.102 mV; the encapsulation rate of 0.04% paeonol sustained-release preparation nano-encapsulation is 63.182～77.6403%, the drug loading is 28.241～41.253%, and the slow release time is as long as 60 hours .
本发明所述的一种丹皮酚纳米缓释制剂，还具有粒径小，分散性强，稳定性好，缓慢释药，靶向性等优点；同时因包裹和吸附丹皮酚而形成聚氰基丙烯酸正丁酯纳米囊，使得丹皮酚的溶解性增加，稳定性增强，药效作用时间延长，药效作用增加，生物利用度增加。A paeonol nano-sustained-release preparation described in the present invention also has the advantages of small particle size, strong dispersibility, good stability, slow drug release, targeting, etc.; The n-butyl cyanoacrylate nanocapsule increases the solubility of paeonol, enhances the stability, prolongs the drug effect time, increases the drug effect, and increases the bioavailability.
本发明同时还提供了上述一种丹皮酚纳米缓释制剂的其制备方法，满足制备工艺简单、制备条件要求简单、制备过程不产生任何有毒有害物质且可用于注射的要求。At the same time, the present invention also provides a preparation method of the above-mentioned paeonol nano-sustained-release preparation, which meets the requirements of simple preparation process, simple preparation conditions, no toxic and harmful substances produced during the preparation process, and can be used for injection.
一种丹皮酚纳米缓释制剂的制备方法，包括以下步骤：A preparation method of paeonol nano sustained-release preparation, comprising the following steps:
步骤一、准确称取丹皮酚和丙酮水溶液或丙酮，将丹皮酚置于丙酮水溶液或丙酮中超声充分溶解得到溶液一，备用；Step 1, accurately weigh paeonol and acetone aqueous solution or acetone, place paeonol in acetone aqueous solution or acetone and ultrasonically dissolve fully to obtain solution 1, set aside;
步骤二、准确量取α-氰基丙烯酸正丁酯和乙酸乙酯充分混合，并立即将所述溶液一加入，混匀，得到溶液二，备用；Step 2. Accurately measure n-butyl α-cyanoacrylate and ethyl acetate and mix thoroughly, and immediately add the solution 1, mix well to obtain solution 2, and set aside;
步骤三、准确称量取泊洛沙姆188、右旋糖苷-70、水，混合后并用盐酸调溶液pH值为1.5～3.5，得到溶液三，备用；Step 3: Accurately weigh poloxamer 188, dextran-70, and water, mix them, and adjust the pH of the solution to 1.5-3.5 with hydrochloric acid to obtain solution 3, which is set aside;
步骤四、将所述溶液二在室温下缓慢逐滴加入到所述溶液三中，并在750～950 r/min的磁力搅拌条件下进行自发界面缩聚合，然后在30～40℃的条件下旋转蒸发除去丙酮，使用5～8微米滤纸过滤，用氢氧化钠调pH值为7.0±0.1，在750～950 r/min的磁力搅拌条件下制得丹皮酚纳米缓释制剂的混悬液，或在-80℃条件下经过48小时冷冻干燥可制得丹皮酚纳米缓释制剂的冻干粉。Step 4: Slowly add the solution 2 to the solution 3 dropwise at room temperature, and carry out spontaneous interfacial polycondensation under the condition of 750-950 r/min magnetic stirring, and then under the condition of 30-40°C Remove acetone by rotary evaporation, filter with 5-8 micron filter paper, adjust the pH value to 7.0±0.1 with sodium hydroxide, and prepare the suspension of paeonol nano-sustained-release preparation under the condition of magnetic stirring at 750-950 r/min , or freeze-dried at -80°C for 48 hours to prepare the freeze-dried powder of paeonol nano-sustained-release preparation.
本发明与现有技术相比较，本发明的实施效果如下：The present invention compares with prior art, and implementation effect of the present invention is as follows:
本发明所述的一种丹皮酚纳米缓释制剂的制备方法，制备工艺简单，耗能低；制备丹皮酚纳米缓释制剂的反应前后均无有害、有毒物质参与或生成，毒性小，安全性高；它不仅可作为丹皮酚的注射剂，控缓释、靶向等制剂，也可最大限度地充分利用丹皮酚的药用价值。The preparation method of a paeonol nano-sustained-release preparation according to the present invention has simple preparation process and low energy consumption; no harmful and toxic substances are involved or generated before and after the reaction of preparing the paeonol nano-sustained-release preparation, and the toxicity is small. High safety; it can not only be used as paeonol injection, controlled slow-release, targeted preparations, etc., but also can make full use of the medicinal value of paeonol.
附图说明Description of drawings
图1为本发明所述的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图；Fig. 1 is a transmission electron microscope (TEM) figure of a kind of paeonol nano-sustained-release preparation according to the present invention;
图2为本发明所述的一种丹皮酚纳米缓释制剂的粒径直观图；Fig. 2 is the direct view of the particle diameter of a kind of paeonol nano sustained-release preparation of the present invention;
图3为本发明所述的一种丹皮酚纳米缓释制剂的释放百分率图。Fig. 3 is a graph of the release percentage of a paeonol nano-sustained-release preparation according to the present invention.
具体实施方式Detailed ways
下面将结合具体的实施例来说明本发明的内容。The content of the present invention will be described below in conjunction with specific embodiments.
具体实施例1Specific embodiment 1
本实施例所述的一种丹皮酚纳米缓释制剂，其原料配比为：A kind of paeonol nano-sustained-release preparation described in the present embodiment, its raw material ratio is:
油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.04克，乙酸乙酯4.0毫升，α-氰基丙烯酸正丁酯0.26毫升；The proportion of oil phase raw materials is: 100 milliliters of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.04 grams of paeonol, 4.0 milliliters of ethyl acetate, and 0.26 milliliters of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.8克，右旋糖苷-70为0.8克。The raw material ratio of the water phase is: 100 ml of ultrapure water, 0.8 g of poloxamer 188, and 0.8 g of dextran-70.
本实施例所述的一种丹皮酚纳米缓释制剂的制备方法，包括以下步骤：A kind of preparation method of paeonol nano-sustained-release preparation described in the present embodiment, comprises the following steps:
步骤一、准确称取丹皮酚和丙酮水溶液或丙酮，将丹皮酚置于丙酮水溶液或丙酮中超声5分钟，充分溶解得到溶液一，备用；Step 1. Accurately weigh paeonol and acetone aqueous solution or acetone, place paeonol in acetone aqueous solution or acetone and sonicate for 5 minutes, fully dissolve to obtain solution 1, and set aside;
步骤二、准确量取α-氰基丙烯酸正丁酯和乙酸乙酯充分混合，并立即将所述溶液一加入，混匀，得到溶液二，备用；Step 2. Accurately measure n-butyl α-cyanoacrylate and ethyl acetate and mix thoroughly, and immediately add the solution 1, mix well to obtain solution 2, and set aside;
步骤三、准确称量取泊洛沙姆188、右旋糖苷-70、水，混合后并用1 mol/L盐酸调溶液pH值为2.5，得到溶液三，备用；Step 3: Accurately weigh Poloxamer 188, dextran-70, and water, mix them, and adjust the pH value of the solution to 2.5 with 1 mol/L hydrochloric acid to obtain Solution 3 for later use;
步骤四、将所述溶液二在室温下磁力搅拌20～30分钟后，缓慢逐滴加入到所述溶液三中，并在750～950 r/min的磁力搅拌条件下进行自发界面缩聚合3～4小时，然后在30～40℃的条件下旋转蒸发除去丙酮，使用5～8微米滤纸过滤，用1 mol/L氢氧化钠调pH值为7.0±0.1，在750～950 r/min的磁力搅拌条件下搅拌1小时制得丹皮酚纳米缓释制剂的混悬液，或在-80℃条件下经过48小时冷冻干燥可制得丹皮酚纳米缓释制剂的冻干粉。Step 4. After stirring the solution 2 magnetically at room temperature for 20-30 minutes, slowly add it to the solution 3 dropwise, and carry out spontaneous interfacial polycondensation under the condition of magnetic stirring at 750-950 r/min for 3- After 4 hours, remove acetone by rotary evaporation at 30-40°C, filter with 5-8 micron filter paper, adjust the pH value to 7.0±0.1 with 1 mol/L sodium hydroxide, and use a magnetic force of 750-950 r/min Stirring under stirring conditions for 1 hour to prepare a suspension of paeonol nano sustained-release preparation, or freeze-drying at -80°C for 48 hours to obtain a freeze-dried powder of paeonol nano sustained-release preparation.
本实施例制得的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图见图1，本实施例制得的一种丹皮酚纳米缓释制剂的粒径直观图见图2。The transmission electron microscope (TEM) image of a paeonol nano-sustained-release preparation prepared in this example is shown in Figure 1, and the particle size visual diagram of a paeonol nano-sustained-release preparation prepared in this example is shown in Figure 2.
以pH值为7.4的0.5％十二烷基硫酸钠磷酸盐缓冲液为释放介质，准确称取丹皮酚对照品溶液4 mg与20毫升释放介质均匀混合，丹皮酚纳米囊混悬液与释放介质均匀混合后总体积为20毫升，转入经蒸馏水浸泡处理过的透析袋中，将透析袋两端扎紧，绑于浆上，分别置于盛有250毫升释放介质的溶出三角瓶中，在恒温（37℃）摇床（120 r/min）中恒速震荡。With 0.5% sodium dodecyl sulfate phosphate buffer solution with a pH value of 7.4 as the release medium, accurately weigh 4 mg of paeonol reference solution and mix it evenly with 20 ml of release medium, paeonol nanocapsule suspension and After the release medium is evenly mixed, the total volume is 20 ml, and transferred to the dialysis bag soaked in distilled water, the two ends of the dialysis bag are tied tightly, tied to the slurry, and placed in the dissolution triangular flask containing 250 ml release medium , shaking at a constant speed in a constant temperature (37°C) shaker (120 r/min).
分别于0.25小时，0.5小时，1小时，2小时，3小时，5小时，7小时，9h，11小时，15小时，23小时，31小时，39小时，51小时，63小时取样2毫升置-20℃冰箱冷冻保存，每次取样后再补充2毫升的释放介质溶液，将所取样品经高速低温离心机2000 r/min、-4℃离心15分钟，取上清液1毫升经0.45微米微孔滤膜过滤，取续滤液。Take 2 ml of samples at 0.25 hours, 0.5 hours, 1 hour, 2 hours, 3 hours, 5 hours, 7 hours, 9 hours, 11 hours, 15 hours, 23 hours, 31 hours, 39 hours, 51 hours, and 63 hours. Store in a refrigerator at 20°C, add 2 ml of release medium solution after each sampling, centrifuge the sample at 2000 r/min at -4°C for 15 minutes at a high-speed low-temperature centrifuge, take 1 ml of the supernatant and wash it through a 0.45 micron micrometer Pore membrane filtration, take the continued filtrate.
采用HPLC法测定不同时间点样品上清液含量，每次进样20 μL，测定丹皮酚的峰面积，并按标准曲线回归方程计算丹皮酚的浓度，得出累积释药百分数并绘制释药曲线，实验结果如图3所示。The HPLC method was used to measure the supernatant content of samples at different time points, each time 20 μL was injected, the peak area of paeonol was determined, and the concentration of paeonol was calculated according to the standard curve regression equation, and the cumulative release percentage was obtained and the release rate was plotted. Drug curve, the experimental results are shown in Figure 3.
具体实施例2Specific embodiment 2
本实施例所述的一种丹皮酚纳米缓释制剂，其原料配比为：A kind of paeonol nano-sustained-release preparation described in the present embodiment, its raw material ratio is:
油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.05克，乙酸乙酯5.0毫升，α-氰基丙烯酸正丁酯0.30毫升；The proportion of oil phase raw materials is: 100 ml of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.05 g of paeonol, 5.0 ml of ethyl acetate, and 0.30 ml of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.5克，右旋糖苷-70为1.0克。The raw material ratio of the aqueous phase is: 100 ml of ultrapure water, 0.5 g of poloxamer 188, and 1.0 g of dextran-70.
本实施例所述的一种丹皮酚纳米缓释制剂的制备方法中，进行自发界面聚合时的混合物pH值为3.0，其余步骤与具体实施例1相同，本实施例制得的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图、粒径直观图以及释放百分率图与具体实施例1相近。In the preparation method of a paeonol nano-sustained-release preparation described in this example, the pH value of the mixture during spontaneous interfacial polymerization is 3.0, and the remaining steps are the same as in Example 1. A kind of paeonol prepared in this example The transmission electron microscope (TEM) image, particle size visualization image and release percentage image of the skin phenol nano-sustained-release preparation are similar to those in Example 1.
具体实施例3Specific embodiment 3
本实施例所述的一种丹皮酚纳米缓释制剂，其原料配比为：A kind of paeonol nano-sustained-release preparation described in the present embodiment, its raw material ratio is:
油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.06克，乙酸乙酯6.0毫升，α-氰基丙烯酸正丁酯0.35毫升；The proportion of oil phase raw materials is: 100 ml of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.06 g of paeonol, 6.0 ml of ethyl acetate, and 0.35 ml of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.6克，右旋糖苷-70为0.8克。The raw material ratio of the aqueous phase is: 100 ml of ultrapure water, 0.6 g of poloxamer 188, and 0.8 g of dextran-70.
本实施例所述的一种丹皮酚纳米缓释制剂的制备方法中，进行自发界面聚合时的混合物pH值为2.0，其余步骤与具体实施例1相同，本实施例制得的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图、粒径直观图以及释放百分率图与具体实施例1相近。In the preparation method of a paeonol nano-sustained-release preparation described in this example, the pH value of the mixture during spontaneous interfacial polymerization is 2.0, and the remaining steps are the same as in Example 1. A paeonol prepared in this example The transmission electron microscope (TEM) image, particle size visualization image and release percentage image of the skin phenol nano-sustained-release preparation are similar to those in Example 1.
具体实施例4Specific embodiment 4
本实施例所述的一种丹皮酚纳米缓释制剂，其原料配比为：A kind of paeonol nano-sustained-release preparation described in the present embodiment, its raw material ratio is:
油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.08克，乙酸乙酯3.0毫升，α-氰基丙烯酸正丁酯0.30毫升；The proportion of oil phase raw materials is: 100 ml of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.08 g of paeonol, 3.0 ml of ethyl acetate, and 0.30 ml of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.7克，右旋糖苷-70为1.1克。The raw material ratio of the water phase is: 100 ml of ultrapure water, 0.7 g of poloxamer 188, and 1.1 g of dextran-70.
本实施例所述的一种丹皮酚纳米缓释制剂的制备方法中，进行自发界面聚合时的混合物pH值为3.5，其余步骤与具体实施例1相同，本实施例制得的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图、粒径直观图以及释放百分率图与具体实施例1相近。In the preparation method of a paeonol nano-sustained-release preparation described in this example, the pH value of the mixture during spontaneous interfacial polymerization is 3.5, and the remaining steps are the same as in Example 1. A paeonol prepared in this example The transmission electron microscope (TEM) image, particle size visualization image and release percentage image of the skin phenol nano-sustained-release preparation are similar to those in Example 1.
具体实施例5Specific embodiment 5
本实施例所述的一种丹皮酚纳米缓释制剂，其原料配比为：A kind of paeonol nano-sustained-release preparation described in the present embodiment, its raw material ratio is:
油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.09克，乙酸乙酯5.0毫升，α-氰基丙烯酸正丁酯0.15毫升；The proportion of oil phase raw materials is: 100 ml of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.09 g of paeonol, 5.0 ml of ethyl acetate, and 0.15 ml of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.4克，右旋糖苷-70为0.6克。The raw material ratio of the aqueous phase is: 100 ml of ultrapure water, 0.4 g of poloxamer 188, and 0.6 g of dextran-70.
本实施例所述的一种丹皮酚纳米缓释制剂的制备方法中，进行自发界面聚合时的混合物pH值为1.5，其余步骤与具体实施例1相同，本实施例制得的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图、粒径直观图以及释放百分率图与具体实施例1相近。In the preparation method of a paeonol nano-sustained-release preparation described in this example, the pH value of the mixture during spontaneous interfacial polymerization is 1.5, and the remaining steps are the same as in Example 1. A paeonol prepared in this example The transmission electron microscope (TEM) image, particle size visualization image and release percentage image of the skin phenol nano-sustained-release preparation are similar to those in Example 1.
具体实施例6Specific embodiment 6
本实施例所述的一种丹皮酚纳米缓释制剂，其原料配比为：A kind of paeonol nano-sustained-release preparation described in the present embodiment, its raw material ratio is:
油相原料配比为：质量浓度大于20%的丙酮水溶液或丙酮100毫升，丹皮酚0.10克，乙酸乙酯4.0毫升，α-氰基丙烯酸正丁酯0.30毫升；The proportion of oil phase raw materials is: 100 ml of acetone aqueous solution or acetone with a mass concentration greater than 20%, 0.10 g of paeonol, 4.0 ml of ethyl acetate, and 0.30 ml of n-butyl α-cyanoacrylate;
水相原料配比为：超纯水100毫升，泊洛沙姆188为0.5克，右旋糖苷-70为0.9克。The raw material ratio of the aqueous phase is: 100 ml of ultrapure water, 0.5 g of poloxamer 188, and 0.9 g of dextran-70.
本实施例所述的一种丹皮酚纳米缓释制剂的制备方法中，进行自发界面聚合时的混合物pH值为2.5，其余步骤与具体实施例1相同，本实施例制得的一种丹皮酚纳米缓释制剂的透射电镜（TEM）图、粒径直观图以及释放百分率图与具体实施例1相近。In the preparation method of a paeonol nano-sustained-release preparation described in this example, the pH value of the mixture during spontaneous interfacial polymerization is 2.5, and the remaining steps are the same as in Example 1. A paeonol prepared in this example The transmission electron microscope (TEM) image, particle size visualization image and release percentage image of the skin phenol nano-sustained-release preparation are similar to those in Example 1.
以上内容是结合具体的实施例对本发明所作的详细说明，不能认定本发明具体实施仅限于这些说明。对于本发明所属技术领域的技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换，都应当视为属于本发明保护的范围。The above content is a detailed description of the present invention in conjunction with specific embodiments, and it cannot be assumed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the technical field of the present invention, without departing from the concept of the present invention, some simple deductions or substitutions can be made, which should be deemed to belong to the protection scope of the present invention.
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| CN201610137190.0ACN105663085B (en) | 2016-03-11 | 2016-03-11 | A kind of Paeonol nano controlled-release preparation and preparation method thereof |
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