WO2016119114A1 - Puerarin nanocrystalline capsule and preparation method therefor - Google Patents

Abstract

A puerarin nanocrystalline capsule and a preparation method therefor. The preparation method comprises: (1) adding puerarin and lauryl sodium sulfate (a mass ratio ≥ 1:5 and < 1:1.5) into water, and mixing uniformly to obtain mixed liquor; (2) homogenizing the mixed liquor (40-45ºC and 700-2000Bar) for 5 times or more to obtain suspension (the particle size being 150-500nm); (3) using a method I or a method II: I pre-freezing the suspension at -50 to -40ºC for 1.5-2.5h, then keeping a temperature at -30 to -20ºC for 3.5-4.5h, lyophilizing under -5ºC for 12-16h, desorption-drying under 25℃ for 1.5-2.5h, smashing, sieving, and filling capsules with the suspension; II spray-drying the suspension at an air inlet under the temperature of 150-200ºC, and filling the capsules with the suspension.

Description

Puerarin nano crystal capsule and preparation method thereof Technical field

The invention relates to a puerarin nanocrystalline capsule and a preparation method thereof.

Background technique

Puerarin, also known as Pueraria lobata, 8-β-D-glucopyranose-4',7-dihydroxyisoflavone, mainly found in the leguminous plant Pueraria lobata (Willd.) Ohwi root or Pueraria lobata P. thunbergiana Benth. Root. Puerarin is colorless crystal; melting point 203 ~ 205 ° C; solubility in water and organic solvents are not large, heating soluble in water, methanol, ethanol, but insoluble in ethyl alcohol, chloroform, benzene; not enzymatic hydrolysis, Also not easily hydrolyzed by dilute acid.

Puerarin has the functions of promoting blood circulation, improving microcirculation, dilating coronary artery and cerebral blood vessels, reducing myocardial oxygen consumption, and promoting the brain circulation and peripheral circulation of animals and human body. It not only improves the normal brain microcirculation of the human body, but also has obvious improvement effects on microcirculatory disorders, mainly manifested by an increase in the amplitude of local microvascular blood flow and movement. Puerarin can also improve the nailfold microcirculation in patients with sudden deafness, which can accelerate the blood flow velocity of microvessels, clear blood vessels and blood stasis, and improve the hearing of patients. Puerarin has a protective effect on hypoxic myocardium. Puerarin can significantly reduce the oxygen consumption of ischemic myocardium and protect the heart from ultrastructural damage caused by ischemia and reperfusion. Puerarin can protect liver injury through gastric absorption, induce apoptosis of activated hepatic stellate cells, effectively reverse chemically induced liver fibrosis, and also protect against acute liver injury induced by carbon tetrachloride, and has many physiological activities. .

At present, the clinical use of puerarin preparations is puerarin injection and puerarin eye drops, clinically used for the treatment of cardiovascular and cerebrovascular diseases and retinal vascular disease, fundus diseases and sudden deafness. Injection is inconvenient to use, and patients often have temporary abdominal distension, nausea and other digestive tract reactions; a small number of patients may have rash, allergic asthma, anaphylactic shock, fever and other allergic reactions, very few patients have hemolysis reaction, poor safety. Oral administration is convenient and safe, but since the water solubility and fat solubility of puerarin are very poor, the solubility in water is 1.1×10 ^-2 mol/L, so oral absorption is poor, and the absolute bioavailability of oral administration is 4 About %, therefore, there is currently no oral administration preparation listed.

Nanocrystallization of puerarin is the main way to improve its oral absorption. Patent 1 (application No.: 201310102810.3) discloses a puerarin nanocrystal composition and a preparation method thereof, the composition of which is mainly composed of puerarin and two stabilizers, the stabilizer I accounts for 10-20%, and the stabilizer II accounts for 2～5%, mainly prepared by a media-milling method into a puerarin mixture suspension with an average particle size of about 300nm. It has been shown in rats that the puerarin nanocrystal suspension of the invention can improve the bioavailability of puerarin. However, there is no specific data, which is about 1 time higher than the drug time curve (estimated absolute bioavailability is less than 10%). Patent No. 2 (Application No. 201010157869.9) discloses a puerarin self-microemulsion composition based on mixed oil and a preparation method thereof, which are composed of puerarin, a mixed oil, an emulsifier, a co-emulsifier, etc., which are prepared by the invention. The puerarin self-microemulsion composition can improve the problems of large emulsion, poor stability and large storage volume of traditional emulsion, and can improve the solubility and dispersion of puerarin, increase the absorption of the drug in vivo, and improve the bioavailability. Rat animal experiments showed that the relative oral bioavailability of the puerarin self-microemulsion composition of the invention was 276.7% (estimated absolute bioavailability of about 10%) with the puerarin suspension as a control. Although these inventions can significantly improve the bioavailability of oral administration of puerarin, since puerarin itself is difficult to absorb by oral administration, the absolute bioavailability is only about 4%, and therefore, the technique of the above invention cannot satisfy the requirements for oral administration ( The absolute bioavailability of oral administration needs to be more than 20%).

Summary of the invention

The technical problem to be solved by the present invention is to overcome the poor solubility of puerarin, it is difficult to absorb by oral administration, and the absolute bioavailability is low (about 4%). Although the prior art can significantly improve the bioavailability of oral administration of puerarin, it cannot A puerarin nanocrystalline capsule and a preparation method thereof are provided, which meet the requirements of oral administration (the absolute bioavailability requirement of oral administration is more than 20%). The capsule is used as an oral preparation. After oral administration, the relative bioavailability of the puerarin suspension is 447%, and the absolute bioavailability is 22% (up to 20%), which significantly increases the oral administration of puerarin. Absorption, greatly improving the oral bioavailability of puerarin, can meet the requirements of oral administration of puerarin, Has a good application prospects.

The invention provides a preparation method of puerarin nanocrystalline capsule, which comprises the following steps:

(1) adding puerarin and sodium lauryl sulfate to water and mixing uniformly to obtain a mixed solution; the mass ratio of puerarin and sodium lauryl sulfate is greater than or equal to (1:5) and less than (1: 1.5);

(2) circulating the mixture for more than 5 times to obtain a puerarin nanocrystal suspension; wherein the homogenization temperature is 40-45 ° C, and the homogenous pressure is 700-2000 Bar; The puerarin nanocrystal suspension has a particle size of 150-500 nm;

(3) Step (3) is carried out in any of the following ways:

Method 1: The puerarin nanocrystal suspension is pre-frozen at -50 to -40 ° C for 1.5 to 2.5 h, then at -30 to -20 ° C for 3.5 to 4.5 h, and then sublimed at -5 ° C for drying 12 ~16h, analytical drying at 25 ° C for 1.5 ~ 2.5h, puerarin nanocrystalline freeze-dried product, crushed, sieved, the powder is filled into the capsule, then;

Method 2: The puerarin nanocrystal suspension is spray-dried at an air inlet temperature of 150-200 ° C to obtain a puerarin nanocrystalline powder, which is filled into a capsule.

In the step (1), the mass volume of the puerarin and the water is preferably (1 to 2) g: (50 to 500) mL, more preferably 1 g: 50 mL.

In the step (1), the puerarin accounts for 40% or less, but is not zero, preferably 30% to 35%; and the sodium lauryl sulfate accounts for 60-80%, preferably 60%. -70%; the percentage is the percentage by mass of the puerarin nanocrystalline freeze-dried product or the puerarin nanocrystalline powder.

In the step (1), the quality of the puerarin and the sodium lauryl sulfate is preferably (1:2) to (1:3).

In the step (1), the mixing is uniform in the art, and it is preferred to mix it evenly with stirring. Wherein, the agitation is preferably magnetic stirring.

In the step (2), the homogenizing device is a conventional device in the art, preferably a high-pressure emulsion homogenizer.

In the step (2), the homogenization temperature is preferably 43 °C.

In the step (2), the homogenous pressure is preferably 700 Bar.

In the step (2), the number of times of the homogenization is preferably from 6 to 15 times, more preferably 10 times.

In the step (2), the particle size of the puerarin nanocrystal suspension is preferably from 100 to 300 nm, more preferably from 242 nm.

In the step (3), the pre-freezing temperature is preferably -45 ° C; and the pre-freezing time is preferably 2 h.

In the step (3), the temperature of the heat preservation is preferably -25 ° C; and the heat retention time is preferably 4 hours.

In the step (3), the sublimation drying time is preferably 14 hours.

In the step (3), the analytical drying time is preferably 2 hours.

In the step (3), the equipment used for the pre-freezing, the heat preservation, the sublimation drying, and the analytical drying is a conventional apparatus in the art, preferably a lyophilizer.

In the step (3), the sieving is conventionally operated in the art, preferably a sieve of 80 mesh.

In the first aspect of the step (3), preferably, a lyoprotectant is further added to the puerarin nanocrystal suspension before the pre-freezing.

Wherein, the lyoprotectant is preferably one or more of mannitol, glucose and sucrose. The amount of the lyoprotectant added is preferably from 0 to 10%, but not zero, more preferably 6%, and the percentage is the mass percentage of the lycopene nanocrystal freeze-dried product.

In the step (3), the spray drying is carried out using a spray dryer conventional in the art. The air inlet temperature is preferably from 170 to 190 ° C, more preferably from 180 ° C. The flow rate of the spray dried feed is conventional in the art, preferably 4-8 rpm, more preferably 8 rpm, and rpm means the number of revolutions per minute depending on the peristaltic pump used in the spray dryer used.

In the present invention, step (3) is preferably selected in a manner of one.

In the present invention, the puerarin nanocrystal obtained by reconstitution of the content of the puerarin nanocrystalline capsule has a particle size of preferably 180-600 nm, more preferably 246 nm.

In the present invention, the particle diameters involved are all measured by a nanoparticle size analyzer.

The present invention also provides a puerarin nanocrystalline capsule prepared by the above preparation method.

Based on the common knowledge in the art, the above various preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

The reagents and starting materials used in the present invention are commercially available.

The positive progress of the invention is that the puerarin nanocrystalline capsule prepared by the invention has high active ingredient content and is convenient for oral administration, and can greatly improve the bioavailability of puerarin (up to 22%) after oral administration, and overcome the clinical situation of injection. Adverse reactions during use make it more convenient and safer than existing preparations in clinical use, and ensure its effectiveness. It can be used clinically to treat coronary heart disease, angina pectoris, myocardial infarction, retinal artery, venous obstruction, suddenness. deaf. The puerarin nanocrystalline capsule provided by the invention has a dosage of 1.0-3.0 g/50 kg body weight per day, which can be determined according to the age, sex and condition of the patient.

DRAWINGS

Fig. 1 is an XRD diffraction pattern of Effect Example 1.

2 is a DSC result of Effect Example 1.

Fig. 3 is a graph showing the drug time of puerarin injection in effect example 2.

4 is a graph showing the drug time of the drug substance, the Pue-PVP nanocrystal capsule, and the Pue-SDS nanocrystal capsule of the effect example 2.

detailed description

The invention is further illustrated by the following examples, which are not intended to limit the invention. The experimental methods in the following examples which do not specify the specific conditions are selected according to conventional methods and conditions, or according to the product specifications.

In the following examples, the 16h particle size refers to the particle size (nm) of the puerarin nanocrystal suspension after standing for 16 hours.

Example 1

Take puerarin 2g, sodium lauryl sulfate 4g, add 100mL water, magnetically stir evenly; add the above mixture into high-pressure milk homogenizer, control the temperature of the preparation process at 43 ° C, and circulate 10 times under 700Bar pressure , puerarin nanocrystal suspension; take puerarin nanocrystal suspension, placed in a freeze dryer at -45 ° C pre-freeze and then freeze-dried (-45 ° C pre-freezing for 2 h, -25 ° C for 4 h, - 5°C sublimation drying for 14h, 25°C analytical drying for 2h out of the box), puerarin nanocrystal freeze-dried product; puerarin nanocrystal freeze-dried product, crushed through 80 mesh sieve, powder filled capsule, then puerarin Nanocrystalline capsules.

Example 2

This embodiment is basically the same as the first embodiment except that the puerarin nanocrystal suspension is taken and lyophilized to spray drying, and spray dried at a flow rate of 180 ° C at a flow rate of 8 rpm to obtain puerarin. The nanocrystalline powder is filled with capsules to obtain puerarin nanocrystalline capsules.

Example 3

Take the same puerarin nanocrystal suspension as in Example 1, add 6% mannitol, freeze-dry in lyophilizer at -20 ° C, and freeze-dry to obtain puerarin nanocrystal freeze-dried product; The lyophilized product of the nanocrystals is pulverized through an 80 mesh sieve, and after the powder is filled into the capsule, the puerarin nanocrystalline capsule is obtained.

Example 4

The raw material components and preparation process of this example were the same as those of Example 1, except that the mass of sodium lauryl sulfate was 5 g.

Example 5

The raw material components and preparation process of this example were the same as those of Example 1, except that the homogenization pressure was 1000 Bar.

Example 6

The raw material components and preparation process of this example were the same as those of Example 1, except that the homogenization pressure was 1500 Bar.

Example 7

The raw material components and the preparation process of the present embodiment are the same as those of the first embodiment, except that the homogenization times are The number is 5 times.

Example 8

The raw material components and preparation process of this example were the same as those of Example 1, except that the number of homogenizations was 20 times.

Effect of different raw material components of Comparative Examples 1-8 on the product

2 g of puerarin (Pue) was added, and different stabilizers were added in the following proportions, 100 mL of water was added, and a puerarin nanocrystal suspension was prepared as in Example 1, as shown in Table 1. The results showed that when puerarin and hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), poloxamer 188 (P188) were 1:1, 1:2 by mass ratio and puerarin and poly When vinylpyrrolidone (PVP) was prepared at a mass ratio of 1:1, it could not be prepared into a suitable puerarin nanocrystal suspension, and it could not be prepared into puerarin nanocrystalline capsules.

Table 1 Comparison of the formulations and results of Comparative Examples 1-8

Effect of different ratios of raw materials in Comparative Examples 9 to 11 on products

The puerarin and SDS were added to 100 mL of water in the following proportions, and the magnetic stirring was uniform. The rest were the same as in Example 1, as shown in Table 2. The results show that when the ratio of puerarin to SDS is greater than or equal to At 1:1.5, it is difficult to prepare a puerarin nanocrystal suspension, and it is impossible to prepare a puerarin nanocrystalline capsule.

Table 2 Comparison of the formulations and results of Comparative Examples 9-11

Comparative Example 11 is a comparative example in which puerarin nanocrystalline capsules were prepared when the remaining conditions were the same as in Example 1, when Pue:SDS was less than 1:5. The results indicate that too high a SDS content may cause intestinal discomfort.

Effect of homogenization pressure of Comparative Example 12 on preparation results

According to the first embodiment, the above mixture was added to a high-pressure milk homogenizer, and the temperature of the preparation process was controlled at 40 ° C, and the mixture was circulated and homogenized 10 times under different pressures. The rest were the same as in Example 1, as shown in Table 3. The results show that the puerarin nanocrystal suspension can be prepared when the homogenization pressure is greater than or equal to 700 Bar, and the puerarin nanocrystalline capsule can also be prepared.

Table 3 Comparison of parameter settings and results of Comparative Example 12

	Homogenization pressure (Bar)	0h particle size (nm)	16h particle size (nm)
				Example 1	700	242.7±7.2	230.8±12.5
Example 5	1000	225.4±8.2	230.1±10.9
				Example 6	1500	211.6±9.7	215.6 ± 7.3
Comparative Example 12	600	>1000nm	>1000nm

Effect of the number of homogenization of Comparative Example 13 on the preparation results

According to the first embodiment, the above mixture is added to a high-pressure emulsion homogenizer, and the temperature of the preparation process is controlled at 40 ° C, and the homogenization is repeated at 700 Bar pressure for different times. The rest is the same as in the first embodiment, as shown in Table 4. The results show that the puerarin nanocrystal suspension can be prepared when the number of homogenization is more than 5 times. Can be prepared into puerarin nanocrystalline capsules.

Table 4 Comparison of parameter settings and results of Comparative Example 13

	Number of homogeneity (times)	0h particle size (nm)	16h particle size (nm)
				Example 1	10	242.7±7.2	230.8±12.5
Example 7	5	336.6±11.5	339.3±13.1
				Example 8	20	205.3 ± 7.9	210.2±9.7
Comparative Example 13	4	>1000nm	>1000nm

Effect of the homogenization temperature of Comparative Example 14～16 on the preparation results

According to the first embodiment, the above mixture was added to a high-pressure emulsion homogenizer to control different temperatures during the preparation process, and the mixture was homogenized 10 times under a pressure of 700 Bar, and the others were the same as in Example 1, as shown in Table 5. The results show that when the temperature is controlled above 40 °C in the homogenization process, the puerarin nanocrystal suspension can be prepared, and the puerarin nanocrystalline capsule can also be prepared, but when the temperature is too high (>46 °C), the mixture is mixed. The stability of the suspension is not good.

Table 5 Comparison of parameter settings and results of Comparative Examples 14-16

	Homogenization temperature (°C)	0h particle size (nm)	16h particle size (nm)
				Example 1	43	242.7±7.2	230.8±12.5
Comparative Example 14	32	>1000nm	>1000nm
				Comparative Example 15	37	760.1±16.7	>1000nm
Comparative Example 16	47	225.4±8.1	527.7±9.8

Comparison of the drying temperature and analytical drying temperature of the comparative examples 17-22 on the preparation results

According to the first embodiment, the pre-freezing temperature remained unchanged during lyophilization, and the sublimation drying and analytical drying were changed. The remaining puerarin nanocrystalline capsules were prepared in the same manner as in Example 1, and the lyophilized powder was reconstituted to determine the particle size. 6. The results show that when the sublimation drying is greater than or less than -5 ° C and the analytical drying is greater than or less than 25 ° C, it is possible to change the particles of the lyophilized powder.

Table 6 Comparison of parameter settings and results of Comparative Examples 17-22

Sublimation drying

Analytical drying

Particle size after reconstitution (nm)

Example 1	-5 ° C, 14 h	25 ° C, 2 h	235.2±11.2
				Comparative Example 17	-10 ° C, 14 h	25 ° C, 2 h	Partial particle size >1000nm
Comparative Example 18	5 ° C, 14h	25 ° C, 2 h	Partial particle size >1000nm
				Comparative Example 19	15 ° C, 14h	25 ° C, 2 h	Partial particle size >1000nm
Comparative Example 20	-5 ° C, 14 h	20 ° C, 2 h	Partial particle size >1000nm
				Comparative Example 21	-5 ° C, 14 h	30 ° C, 2 h	Partial particle size >1000nm
Comparative Example 22	-5 ° C, 14 h	40 ° C, 2 h	Partial particle size >1000nm

Effect Example 1

The contents of the puerarin nanocrystalline capsule obtained in Example 1 were sampled and analyzed by X-ray diffraction (XRD) and differential scanning calorimetry (DSC), respectively. The results are shown in Fig. 1 and Fig. 2. In Fig. 1, the A curve represents puerarin, the B curve represents a physical mixture of puerarin and SDS, the C curve represents SDS, and the D curve represents nanocrystalline lyophilized powder. In Fig. 2, the A curve represents puerarin, the B curve represents a nanocrystalline lyophilized powder, the C curve represents a physical mixture of puerarin and SDS, and the D curve represents SDS. The results showed that the crystallization peak of puerarin itself disappeared after preparation of puerarin nanocrystals, and it has become amorphous, indicating that puerarin crystals have been fused in SDS.

Effect Example 2

Effect of puerarin nanocrystalline capsule on the bioavailability of oral administration of puerarin Beagle dog

(1) Experimental materials

Puerarin, 98%, the percentage is mass percentage, provided by Shanghai Kangting Biotechnology Co., Ltd.; Pueraria Injection, provided by Zhejiang Kangenbei Pharmaceutical Co., Ltd. (2mL: 0.1g, batch number: 130201); Pueraria A nanocrystalline capsule was prepared according to the method of Example 1; a puerarin nanocrystalline (PVP) capsule was prepared according to the method of Comparative Example 8.

20 Beagle dogs, 12 months old, weighing 8-11Kg, were provided by the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine.

(2) Method

The puerarin powder was placed in a common capsule to prepare a puerarin capsule, each containing 0.1 g of puerarin.

20 Beagle dogs were randomly divided into 4 groups, 5 in each group. The first group received intravenous injection of puerarin injection; the second group received oral administration of puerarin capsules, and the third group received puerarin nanocrystalline (PVP) capsules. The group was given puerarin nanocrystalline capsules, and each was administered at 50 mg/kg. After administration, blood was taken at 5 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, and 2 mL of blood was taken each time. The collected blood was placed in a centrifuge at 3000 r. Centrifuge at /min for 10 min, take the supernatant, and place in a -20 °C refrigerator for testing.

Determination method: octadecylsilane bonded silica as a packed column, 0.1% citric acid: methanol (75:25) as mobile phase, flow rate 1.0mL / min, detection wavelength is 250nm, according to 250uL plasma +250uL 5% high Chloroacid methanol solution +500uL Pue standard solution +100uL internal standard solution was added, vortexed for 3min, then centrifuged at 12000r/min for 10min, and the supernatant was taken for 10uL injection. Each concentration was injected into three needles to average The value establishes a standard curve. The Pue standard solutions were: 0.05, 0.1, 0.25, 0.5, 1, 2.5, 5, 10 ug/mL. The concentration of p-hydroxybenzoic acid (internal standard) was 32.8 ug/mL.

The sample was added according to the ratio of 10 uL internal standard solution + 50 uL plasma + 50 uL 5% perchloric acid methanol solution, and the sample was placed on a vortex for 3 min, then centrifuged at 12000 r/min for 10 min, and the supernatant was taken for 10 uL to record the peak area and substituted. Blood concentration can be obtained from the standard.

(3) Results

The pharmacokinetic parameters of Pue suspension, Pue-PVP nanocrystalline capsules and Pue-SDS nanocrystalline capsules and puerarin injection in Beagle dogs are shown in Table 7.

Table 7 Experimental results

The results in Table 7 show that the nanocrystalline capsules prepared by using the SDS as the stabilizer in the first embodiment of the present invention can make the absolute bioavailability of puerarin more than 20%, 4.47 times higher than the puerarin bulk drug, and can realize puerarin. Oral administration, while nanocrystals with PVP as a stabilizer cannot improve the bioavailability of puerarin. The drug-time curve of puerarin injection is shown in Figure 3, and the drug-time curves of the other three samples are shown in Figure 4.

While the invention has been described with respect to the preferred embodiments of the embodiments of the embodiments of the invention modify. Accordingly, the scope of the invention is defined by the appended claims.

Claims (10)

1. A method for preparing puerarin nanocrystalline capsules, comprising the steps of:

   (1) adding puerarin and sodium lauryl sulfate to water and mixing uniformly to obtain a mixed solution; wherein the mass ratio of the puerarin to sodium lauryl sulfate is greater than or equal to (1:5) and less than ( 1:1.5);

   (2) circulating the mixture for more than 5 times to obtain a puerarin nanocrystal suspension; wherein the homogenization temperature is 40-45 ° C, and the homogenous pressure is 700-2000 Bar; The puerarin nanocrystal suspension has a particle size of 150-500 nm;

   (3) Step (3) is carried out in any of the following ways:

   Method 1: The puerarin nanocrystal suspension is pre-frozen at -50 to -40 ° C for 1.5 to 2.5 h, then at -30 to -20 ° C for 3.5 to 4.5 h, and then sublimed at -5 ° C for drying 12 ~16h, analytical drying at 25 ° C for 1.5 ~ 2.5h, puerarin nanocrystalline freeze-dried product, crushed, sieved, the powder is filled into the capsule, then;

   Method 2: The puerarin nanocrystal suspension is spray-dried at an air inlet temperature of 150-200 ° C to obtain a puerarin nanocrystalline powder, which is filled into a capsule.
2. The preparation method according to claim 1, wherein in the step (1), the mass to volume ratio of the puerarin to the water is (1 to 2) g: (50 to 500) mL; the puerarin The content is 40% or less, but not zero; the sodium lauryl sulfate accounts for 60-80%; the percentage is the lycopene nanocrystal freeze-dried product or the puerarin nanocrystalline powder Percentage of mass.
3. The preparation method according to claim 2, wherein, in the step (1), the mass to volume ratio of the puerarin to the water is 1 g: 50 mL; the puerarin accounts for 30% to 35%; Sodium lauryl sulfate accounts for 60% to 70%.
4. The preparation method according to at least one of claims 1 to 3, wherein in the step (1), the mass ratio of the puerarin to the sodium lauryl sulfate is (1:2) ～ ( 1:3).
5. The preparation method according to at least one of claims 1 to 4, wherein in the step (2), the apparatus for homogenization is a high-pressure emulsion homogenizer; the homogenization temperature is 43 ° C; Homogenization The pressure is 700 Bar; the number of homogenization cycles is 6-15 times; the particle size of the puerarin nanocrystal suspension is 100-300 nm.
6. The preparation method according to claim 5, wherein the number of times of homogenization is 10 times; and the particle size of the puerarin nanocrystal suspension is 242 nm.
7. The preparation method according to at least one of claims 1 to 6, wherein in the step (3), the pre-freezing temperature is -45 ° C; the pre-freezing time is 2 h; The temperature is -25 ° C; the incubation time is 4 h; the sublimation drying time is 14 h; the analytical drying time is 2 h; the pre-freezing, the heat preservation, the sublimation drying and the The equipment used for the analytical drying is a lyophilizer; the sieving is a sieve of 80 mesh.
8. The preparation method according to at least one of claims 1 to 7, wherein the step (3) is performed in a manner of one; in the first method, before the pre-freezing, the puerarin nanocrystal is suspended. Adding a lyoprotectant to the liquid; the lyoprotectant is added in an amount of 0-10%, but not zero, the percentage being the mass percentage of the puerarin nanocrystal freeze-dried product;

   In the second mode, the spray drying is carried out by using a spray dryer; the air inlet temperature is 170-190 ° C, and the spray drying feed flow rate is 4-8 rpm;

   The puerarin nanocrystals obtained by reconstitution of the content of the puerarin nanocrystalline capsule have a particle size of 180-600 nm.
9. The preparation method according to claim 8, wherein the lyoprotectant is one or more of mannitol, glucose and sucrose; the amount of the lyoprotectant added is 6%; The air inlet temperature is 180 ° C, the spray drying feed flow rate is 8 rpm;

   The content of the puerarin nanocrystal obtained by reconstitution of the content of the puerarin nanocrystalline capsule is 246 nm.
10. A puerarin nanocrystalline capsule obtained by the preparation method according to any one of claims 1 to 9.

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