Lily polysaccharide ultrafine particle preparation method

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a lily polysaccharide ultrafine particle preparation method which comprises the following steps: step 1, preparing a solution: dissolving lily polysaccharide in pure water to prepare a lily polysaccharide aqueous solution with the concentration of 1-20mg / ml; step 2, spray drying: carrying out spray drying on the lily polysaccharide aqueous solution obtained in the step 1 by using a spray dryer to obtain lily polysaccharide ultrafine particles, and controlling the air inlet temperature of spray drying to be 1100-250 DEG C and the feeding rate to be 1-10ml / min; and step 3, collecting and storing: packaging and sealing the dry particles obtained in the step 2 to obtain the finished product lily polysaccharide superfine particles. According to the preparation method, the lily polysaccharide powder is adopted as a raw material, and the lily polysaccharide powder aerosol particles which are appropriate in size, uniform in morphology, good in vitro aerodynamic performance and capable of achieving effective drug pulmonary delivery are prepared through spray drying under the condition that other reagent materials are not used.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a method for preparing ultrafine lily polysaccharide particles. Background Art

[0002] Lily is a perennial bulbous plant of the genus Lilium in the Liliaceae family. It has a wide variety of resources and rich nutrition. It is an excellent economic crop with both edible and medicinal value. The main components of lily are starch, protein, pectin and various biologically active ingredients, such as polysaccharides, steroidal saponins, phenols and alkaloids. Lily polysaccharide is one of the important functional components of lily. It is mainly composed of C, H and a small amount of S elements. It has become a research hotspot in recent years because of its multiple biological activities such as lowering blood sugar, inhibiting bacteria, anti-fatigue, enhancing immunity, anti-tumor, and delaying lung tissue fibrosis. Studies have shown that lily polysaccharide has a good blood sugar-lowering effect.

[0003] As one of the main active ingredients of traditional Chinese medicine, Chinese herbal polysaccharides have the effects of reducing oxidative stress, inhibiting inflammatory response, regulating intestinal flora, and improving insulin resistance. The use of plant polysaccharides provides a new idea for the development of effective hypoglycemic drugs to treat diabetes. However, the preparation of existing plant polysaccharide particles usually requires the help of other carriers and excipients, and has poor dispersibility. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and propose a method for preparing ultrafine particles of lily polysaccharide, which can accurately control the spray drying environment of the particle size and distribution of lily polysaccharide without the aid of other carriers and auxiliary materials, thereby being able to control the preparation of ultrafine particles of lily polysaccharide with a micro-nano wrinkled structure and excellent dispersibility.

[0005] The technical solution adopted by the present invention to solve the technical problem is:

[0006] A method for preparing ultrafine lily polysaccharide particles comprises the following steps:

[0007] Step 1, preparing a solution: dissolving lily polysaccharide in pure water to prepare a lily polysaccharide aqueous solution with a concentration of 1 to 20 mg / ml;

[0008] Step 2, spray drying: using a spray dryer, spray drying the lily polysaccharide aqueous solution obtained in step 1 to obtain lily polysaccharide ultrafine particles, the spray drying air inlet temperature is 100-250° C., and the feed rate is 1-10 ml / min;

[0009] Step 3, collection and preservation: the dry particles obtained in step 2 are packaged and sealed to obtain finished lily polysaccharide ultrafine particles.

[0010] Furthermore, the spray drying air inlet temperature is 150-180°C.

[0011] Furthermore, the lily polysaccharide aqueous solution is 5-7 mg / ml.

[0012] Furthermore, the spray drying feed rate is 2.52-5.88 ml / min.

[0013] Furthermore, the concentration of the lily polysaccharide aqueous solution is 5 mg / ml, the spray drying inlet air temperature is 165° C., and the feed rate is 4.2 ml / min.

[0014] Furthermore, the concentration of the lily polysaccharide aqueous solution is 5 mg / ml, the spray drying inlet air temperature is 180° C., and the feed rate is 4.2 ml / min.

[0015] Furthermore, the concentration of the lily polysaccharide aqueous solution is 7 mg / ml, the spray drying inlet air temperature is 150° C., and the feed rate is 4.8 ml / min.

[0016] Furthermore, the concentration of the lily polysaccharide aqueous solution is 7 mg / ml, the spray drying inlet air temperature is 165° C., and the feed rate is 4.2 ml / min.

[0017] Furthermore, the particle size of the ultrafine lily polysaccharide particles is 1 to 10 μm.

[0018] Technical effects of the present invention:

[0019] Compared with the prior art, the method for preparing ultrafine lily polysaccharide particles of the present invention has the following advantages:

[0020] Beneficial effects:

[0021] The present invention uses lily polysaccharide powder as a raw material, and without using reagent materials that may be toxic to the human body and have a negative impact on the environment, prepares lily polysaccharide powder aerosol particles with suitable size, uniform morphology, good in vitro aerodynamic performance, and capable of achieving effective drug delivery to the lungs through spray drying;

[0022] Compared with oral preparations, the lily polysaccharide powder spray prepared by the present invention can avoid the first-pass effect of the liver and reduce the hepato-renal toxicity of the drug. In addition, the lungs are rich in capillaries, the drug is absorbed quickly, and the bioavailability of the drug is improved.

[0023] The preparation method adopted by the present invention has the advantages of simple operation, stable products, high production efficiency, low energy consumption, etc. in industrial production. The drug can be administered by inhalation, which effectively reduces the dosage, improves the drug administration efficiency, and takes effect quickly.

[0024] The invention obtains high-yield ultrafine lily polysaccharide ultrafine particles under the coordinated coordination of spray drying inlet temperature, solution concentration and feed rate, thereby improving its atomization performance and enhancing the blood sugar lowering effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a schematic diagram showing the effect of the spray drying air inlet temperature on the yield and particle size of lily polysaccharides in the present invention;

[0026] Figure 2 This is a schematic diagram showing the effect of the concentration of the spray drying solution on the yield and particle size of lily polysaccharides in the present invention;

[0027] Figure 3 This is a schematic diagram showing the effect of the spray drying feed rate on the yield and particle size of lily polysaccharide in the present invention;

[0028] Figure 4 This is a scanning electron microscope image of lily polysaccharide powder aerosol particles prepared based on spray drying in Example 1;

[0029] Figure 5 This is a differential scanning calorimetry diagram of the lily polysaccharide powder aerosol particles prepared based on spray drying in Example 1;

[0030] Figure 6 This is a graph showing the mass ratio of lily polysaccharide powder aerosol particles deposited in various collectors of the Next Generation Pharmaceutical Impactor (NGI) prepared based on spray drying in Example 1. DETAILED DESCRIPTION

[0031] The technical solution of the present invention is described in detail below through specific embodiments, but the protection scope of the present invention is not limited to the embodiments.

[0032] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0033] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0034] Embodiment 1:

[0035] The present embodiment relates to a method for preparing ultrafine lily polysaccharide particles, comprising the following steps:

[0036] Step 1, solution preparation: weigh 2.5g lily polysaccharide, dissolve in 500ml pure water, stir magnetically to fully dissolve, the concentration is 5mg / ml, and place in a beaker;

[0037] Step 2, spray drying: using a small spray dryer H-Spray Mini sold by Beijing Halls Biotechnology Co., Ltd., spray drying the liquid obtained in step 1 at an inlet air temperature of 165° C. and a feed rate of 4.2 ml / min to obtain the lily polysaccharide powder aerosol particles;

[0038] Step 3, collection and storage: Pack and seal the qualified dry particles obtained in step 2, and store the finished product in a cool and dry place at low temperature.

[0039] Embodiment 2:

[0040] The present embodiment relates to a method for preparing ultrafine lily polysaccharide particles, comprising the following steps:

[0041] Step 1, solution preparation: weigh 2.5g lily polysaccharide, dissolve in 500ml pure water, stir magnetically to fully dissolve, the concentration is 5mg / ml, and place in a beaker;

[0042] Step 2, spray drying: using a small spray dryer H-Spray Mini sold by Beijing Halls Biotechnology Co., Ltd., spray drying the liquid obtained in step 1 at an inlet air temperature of 180° C. and a feed rate of 4.2 ml / min to obtain the lily polysaccharide powder aerosol particles;

[0043] Step 3, collection and storage: Pack and seal the qualified dry particles obtained in step 2, and store the finished product in a cool and dry place at low temperature.

[0044] Figure 1 , Figure 2 and Figure 3 Schematic diagram of the effects of spray drying inlet temperature (solution concentration = 5 mg / ml, feed rate = 4.2 ml / min), solution concentration (inlet temperature = 165°C, feed rate = 4.2 ml / min), and feed rate (inlet temperature = 165°C, solution concentration = 5 mg / ml) on the yield and particle size of lily polysaccharide.

[0045] Experimental Example 1:

[0046] Characterization of the physical and chemical properties of lily polysaccharide powder aerosol particles:

[0047] The powder aerosol particle product obtained in Example 1 was placed under a laser particle size analyzer for analysis, and the D50 was 3.23 μm;

[0048] The powder aerosol particle product obtained in Example 1 was placed under a scanning electron microscope to take a SEM picture. The SEM picture of the powder aerosol particle product taken by scanning electron microscope is shown in Figure 4 , showing a spherical particle morphology with indentations on the surface;

[0049] The powder aerosol particle product obtained in Example 1 was placed under differential scanning calorimetry for analysis. The DSC graph of the powder aerosol particle product obtained is shown in FIG. Figure 5 , appears amorphous.

[0050] Experimental Example 2:

[0051] Aerodynamic performance evaluation of lily polysaccharide powder aerosol granule products:

[0052] The 10 capsules containing the powder inhaler of Example 1 were separated using a new generation pharmaceutical disc impactor NGI, with the air flow rate set at 60 L / min, and the number of particles deposited on each stage was determined by gravimetric analysis. The dry powder particle mass ratio of the obtained powder inhaler particle product in each stage of the NGI collector is shown in the figure Figure 6 , most of the particles are deposited in the 2nd to 5th layers, which is consistent with the particle size test results and meets the inhalation size.

[0053] Experimental Example 3:

[0054] Animal experiment on the evaluation of hypoglycemic effect of ultrafine lily polysaccharide particles

[0055] 1. Materials and Methods

[0056] 1.1 Sample: The sample prepared in Example 1.

[0057] 1.2 Animals: Male SPF-grade C57BL / 6 mice (6 weeks old, 20±2 g) were purchased from Nanjing Zhonghua Biotechnology Co., Ltd.

[0058] 1.3 Instruments and reagents: High-fat feed, purchased from Beijing Boaigang Biotechnology Co., Ltd.; Streptozotocin, purchased from Shanghai MacLean Biochemical Technology Co., Ltd.; Blood glucose meter, purchased from Roche.

[0059] 1.4 Experimental methods: 20 6-week-old SPF C57BL / 6 mice were selected and adaptively raised for 1 week with free food and water. Five mice were randomly selected as blank control group and fed with basic feed, and the remaining 15 mice were fed with high-fat feed as experimental group. After 6 weeks, mice in the experimental group were intraperitoneally injected with fresh STZ buffer (60 mg / kg) for three consecutive days, and mice in the blank control group were injected with the same volume and concentration of saline buffer. Fasting blood glucose was measured after 1 week. Fasting blood glucose values ​​greater than 11.1 mmol / L and polydipsia, polyphagia, and polyuria were considered to be successful models. They were randomly divided into model group, polysaccharide oral group (100 mg / kg / d), and polysaccharide inhalation group (100 mg / kg / d), with 5 mice in each group. During the entire animal experiment, the healthy mice in the blank control group were fed with basic feed, and the model group, polysaccharide oral group, and polysaccharide inhalation group were fed with high-fat feed. After 5 consecutive days of administration, fasting for 10 hours, fasting blood glucose levels were measured, and the effects of the test substance on the fasting blood glucose of normal animals were observed.

[0060] 2. Results

[0061] Table 1 Effect of the lily polysaccharide dry powder granules of the present invention on fasting blood glucose in hyperglycemic mice

[0062]

[0063] The experimental results show that the particles of the present invention have no effect on the fasting blood sugar of normal mice, lily polysaccharide has a hypoglycemic effect at a dose of 100 mg / kg / d, and the effect of the inhalation administration group is significantly better than that of the oral administration group.

[0064] The above-mentioned specific implementation modes are only specific cases of the present invention. The patent protection scope of the present invention includes but is not limited to the above-mentioned specific implementation modes. Any appropriate changes or modifications made thereto by any ordinary technician in the technical field in accordance with the claims of the present invention shall fall within the patent protection scope of the present invention.

Claims

1. A method for preparing ultrafine lily polysaccharide particles, characterized in that: The following steps are involved: Step 1, preparing a solution: dissolving lily polysaccharide in pure water to prepare a lily polysaccharide aqueous solution with a concentration of 1 to 20 mg / ml; Step 2, spray drying: using a spray dryer, spray drying the lily polysaccharide aqueous solution obtained in step 1 to obtain lily polysaccharide ultrafine particles, the spray drying air inlet temperature is 100-250° C., and the feed rate is 1-10 ml / min; Step 3, collection and preservation: the dry particles obtained in step 2 are packaged and sealed to obtain finished lily polysaccharide ultrafine particles.

2. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The spray drying air inlet temperature is 150-180°C.

3. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The lily polysaccharide aqueous solution is 5-7 mg / ml.

4. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The spray drying feed rate was 2.52-5.88 ml / min.

5. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The concentration of the lily polysaccharide aqueous solution is 5 mg / ml, the spray drying inlet air temperature is 165° C., and the feed rate is 4.2 ml / min.

6. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The concentration of the lily polysaccharide aqueous solution is 5 mg / ml, the spray drying inlet air temperature is 180° C., and the feed rate is 4.2 ml / min.

7. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The concentration of the lily polysaccharide aqueous solution is 7 mg / ml, the spray drying inlet air temperature is 150° C., and the feed rate is 4.8 ml / min.

8. The method for preparing ultrafine lily polysaccharide particles according to claim 1, characterized in that: The concentration of the lily polysaccharide aqueous solution is 7 mg / ml, the spray drying inlet air temperature is 165° C., and the feed rate is 4.2 ml / min.

9. The method for preparing ultrafine lily polysaccharide particles according to any one of claims 1 to 8, characterized in that: The particle size of the lily polysaccharide ultrafine particles is 1 to 10 μm.

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