Valsartan solid self-microemulsion resin drug delivery system as well as preparation method and application thereof

Abstract

The invention discloses a valsartan solid self-microemulsion resin drug loading system and a preparation method and application thereof.The self-microemulsion is prepared through a solid carrier adsorption method, a solid carrier is ion exchange resin, and the drug loading system further comprises the following components for preparing the valsartan liquid self-microemulsion: valsartan, a liquid self-microemulsion oil phase, an emulsifier and a co-emulsifier; according to the invention, the macroporous ion exchange resin is adopted to cure the liquid self-microemulsion, and the solid carrier adsorption method is adopted to prepare the solid self-microemulsion, compared with other curing methods, the amount of the adsorbed liquid self-microemulsion can reach 70%, and the formed powder has good fluidity. And the liquid self-microemulsion is cured into spherical particles with uniform particle size and good morphology by a solid carrier adsorption method, so that the solubility of the medicine with poor water solubility is improved, quick release is realized, the oral bioavailability of the medicine is improved, and the problem of poor solubility of valsartan is solved.

Description

Technical Field

[0001] The invention relates to the field of pharmaceutical preparations, and in particular to a valsartan solid self-microemulsifying resin drug-carrying system and a preparation method and application thereof. Background Art

[0002] Valsartan (VST), molecular formula is C 24 H 29 N5O3, chemically named N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine, is a tetrazole derivative containing a carboxylic acid group. It is white crystals or white, off-white powder, easily soluble in methanol and anhydrous ethanol, slightly soluble in ethyl acetate, and almost insoluble in water. It is an angiotensin II receptor blocker with high selectivity for AT1 receptors, which can effectively inhibit vasoconstriction, the release of aldosterone and adrenaline, and restore the patient's blood pressure to normal levels; in addition, it can also be used to treat non-small cell lung cancer, early diabetic nephropathy, and assist in the treatment of chronic heart failure in the elderly.

[0003] Although valsartan has a long-lasting and stable antihypertensive effect and few toxic and side effects, it belongs to BCS Class II drugs and has poor water solubility, resulting in its bioavailability of only about 23%. Self-microemulsion is an isotropic mixture composed of a natural or synthetic oil phase, a solid or liquid surfactant or one or more hydrophilic solvents and a cosolvent / surfactant. It has thermodynamic stability and forms an O / W type emulsion of less than 100 nm under the peristalsis of gastrointestinal fluid after oral administration. The emulsion formed by self-emulsification has a smaller particle size, which can improve the solubility of the drug, promote drug absorption through lymphatic transport, and prevent first-pass metabolism in the liver. However, self-microemulsions are usually encapsulated in soft gelatin capsules, with limited dosage form choices. During long-term storage, the oil phase and emulsifier can interact with the capsule shell, resulting in leakage. Therefore, the development of more methods for solid self-microemulsions has become a research focus.

[0004] As an emerging drug carrier, ion exchange resin releases drugs into the patient's body by ion exchange. In recent years, ion exchange resin has attracted widespread attention due to its special nano-micro interface structure and its potential application value in pharmacy. Given the characteristics that both acidic and basic drugs can be adsorbed and dispersed inside ion exchange resins, it has derived many advantages, such as masking the bad taste of drugs, promoting the dissolution of poorly soluble drugs, improving the stability of drug dissolution in the storage environment and in vivo, and controlling the slow release of drugs.

[0005] At present, there are few patents on solid self-emulsification, and there are certain problems. Chinese patent CN102600076A discloses a cyclosporine solid self-emulsification particle and a preparation method thereof. By using spherulite granulation technology, cyclosporine A self-emulsification is added to a polymer material, a dispersing carrier, and a porogen dissolved in a solvent to form a uniform suspension solution of the polymer material, and then added to a poor solvent containing a surfactant to prepare cyclosporine A solid self-emulsification particle in a liquid phase in one step. However, the invention does not disclose the in vitro release data and in vivo pharmacokinetic data of the solid self-emulsification particle. Another Chinese patent CN103446234A discloses a multi-component multi-phase solid self-microemulsion of Danshen, its application in the preparation of medicines and its preparation method, wherein the solid self-microemulsion composition is composed of a multi-component extract of Danshen, an emulsifier, an auxiliary emulsifier, an oil phase and a solid adsorbent, and the weight ratio of each component is: multi-component extract of Danshen: 0.1-10g, emulsifier: 10-30g, auxiliary emulsifier: 5-20g, oil phase: 10-30g, solid adsorbent: 20-50g, but the patent does not disclose the in vitro release data of the solid self-microemulsion mixture. In particular, there are almost no patents for solidifying liquid self-microemulsions using macroporous ion exchange resins.

[0006] Therefore, developing a solid self-microemulsifying resin drug delivery system with good stability, simple preparation method, high valsartan content and high solubility is the research focus in this field. Summary of the invention

[0007] Purpose of the invention: In order to solve the problems existing in the prior art, the present invention proposes a valsartan solid self-microemulsification resin drug delivery system and its preparation method and application, which not only has good solubility, fast drug release speed and high oral bioavailability, but also solidifies the liquid self-microemulsion into spherical particles with uniform particle size and good morphology through solid carrier adsorption method, thereby improving the solubility of drugs with poor water solubility, achieving rapid release and improving their oral bioavailability.

[0008] Technical solution: To achieve the above purpose, the present invention adopts the following technical solution:

[0009] A valsartan solid self-microemulsifying resin drug-carrying system adopts a solid carrier adsorption method to prepare a self-microemulsion, wherein the solid carrier is an ion exchange resin, and the drug-carrying system also comprises the following components for making a valsartan liquid self-microemulsion: valsartan, a liquid self-microemulsifying oil phase, an emulsifier and an auxiliary emulsifier; wherein the mass ratio of valsartan, the liquid self-microemulsifying oil phase, the emulsifier and the auxiliary emulsifier is 1:1-2:3-5:1-2; and the mass ratio of the valsartan liquid self-microemulsion to the ion exchange resin is 1:1-3.

[0010] The ion exchange resin is a macroporous ion exchange resin. Macroporous ion exchange resin refers to an insoluble and infusible polymer with a macroporous structure and a network structure with functional groups. Macroporous resins generally have a pore size of more than 10nm and a surface area of ​​5m 2 / g, the difference between true density and apparent density is not less than 0.059 / mL resin, the size and shape of the pores do not change with environmental conditions, it is opaque and milky white in wet state, and is easy to penetrate solvents.

[0011] Furthermore, the liquid self-microemulsified oil phase includes any one of isopropyl myristate, Campul MCMC-8EP / NF monocaprylic glyceride, and Labrafil M 2125CS linoleoyl polyoxyethylene-6 glyceride, or a combination of at least two thereof.

[0012] Preferably, the oil phase is Campul MCMC-8EP / NF (glyceryl monocaprylate).

[0013] Furthermore, the emulsifier includes any one of Tween 20, Tween 80 and Span 80.

[0014] Preferably, the emulsifier is Tween 80.

[0015] Furthermore, the co-emulsifier is diethylene glycol monoethyl ether, polyethylene glycol 400

[0016] (PEG400) or n-butanol.

[0017] Preferably, the co-emulsifier is diethylene glycol monoethyl ether.

[0018] The present invention discloses a method for preparing the valsartan solid self-microemulsifying resin drug-carrying system, comprising the following steps:

[0019] S1. Preparation of valsartan liquid self-microemulsion: weigh the liquid self-microemulsion oil phase, emulsifier and co-emulsifier according to proportion and mix them evenly, place the mixture in a constant temperature water bath and stir to mix evenly, then add valsartan, and continue stirring until a transparent and clear valsartan liquid self-microemulsion is obtained;

[0020] S2, pulverizing of ion exchange resin: take ion exchange resin and add it into a multifunctional pulverizer, after pulverizing, take it out and pass it through a 40-80 mesh sieve;

[0021] S3, preparation of valsartan solid self-microemulsification resin: weigh the valsartan liquid self-microemulsification obtained in S1 and place it in a round-bottom flask, add anhydrous ethanol, add ion exchange resin, wrap the outside of the round-bottom flask with tin foil, and stir magnetically at room temperature to make the valsartan liquid self-microemulsification fully contact with the ion exchange resin so that the valsartan liquid self-microemulsification is fully adsorbed;

[0022] S4. After mixing evenly, place the mixture on a vacuum rotary evaporator. Slowly perform vacuum rotary evaporation in a water bath. Use a medicine spoon to scrape the solid self-microemulsion from the round-bottom flask and pass it through a 40-80 mesh sieve to obtain the valsartan solid self-microemulsion resin drug delivery system.

[0023] Furthermore, the preparation method comprises the following steps:

[0024] S1. Preparation of valsartan liquid self-microemulsion: weigh the liquid self-microemulsion oil phase, emulsifier and co-emulsifier in proportion and mix them evenly, and place the mixture in a constant temperature water bath at 25-50° C. and stir at a stirring speed of 200-500 r / min. After stirring for 20-40 min, add valsartan, and continue stirring for 0.5-2 h to obtain a transparent and clear valsartan liquid self-microemulsion;

[0025] S2. Grinding of ion exchange resin: add ion exchange resin to a multifunctional grinder and grind for 20-40 minutes. After the grinding is completed, take out and pass through a 40-80 mesh sieve;

[0026] S3, preparation of valsartan solid self-microemulsification resin: weigh S1 to obtain valsartan liquid self-microemulsification, place it in a round-bottom flask, add 10-20 mL of anhydrous ethanol, add ion exchange resin in a ratio of 2:1-4:1, wrap the outside of the round-bottom flask with tin foil, and stir magnetically at room temperature for 0.5-1.5 h to allow the valsartan liquid self-microemulsification to fully contact the ion exchange resin so that the valsartan liquid self-microemulsification is fully adsorbed;

[0027] S4. After mixing evenly, place the mixture on a vacuum rotary evaporator and slowly perform vacuum rotary evaporation in a water bath at 35-45°C for 20-40 minutes. After the rotary evaporation is completed, gently scrape the solid self-microemulsion from the round-bottom flask with a medicine spoon and pass it through a 40-80 mesh sieve to obtain the valsartan solid self-microemulsion resin drug delivery system.

[0028] The valsartan solid self-microemulsifying resin prepared by the invention is in the form of white powder, which is quickly dispersed in water, and has a particle size of 300-500nm after dispersion, and is in a regular spherical shape.

[0029] The invention also discloses application of the valsartan solid self-microemulsification resin drug-carrying system in preparing hypertension drugs.

[0030] The invention also discloses the application of the valsartan solid self-microemulsification resin drug-carrying system, which is to fill it into a capsule shell to make a capsule or to press it into a tablet.

[0031] Beneficial effects: Compared with the prior art, the present invention has the following advantages: 1) The present invention uses macroporous ion exchange resin to solidify liquid self-microemulsion to obtain valsartan solid self-microemulsion resin drug-carrying system. The present invention uses solid carrier adsorption method to prepare solid self-microemulsion. Compared with other solidification methods: spherulite granulation technology, liquid-solid compression technology, spray drying technology, freeze drying technology, the preparation process is simple, the amount of adsorbed liquid self-microemulsion can reach 70%, and the formed powder has good fluidity. 2) The solid self-microemulsion resin drug-carrying system of the present invention solidifies the liquid self-microemulsion into spherical particles with uniform particle size and good morphology by solid carrier adsorption method, thereby improving the solubility of drugs with poor water solubility, achieving rapid release, improving its oral bioavailability, solving the problem of poor solubility of valsartan, and applying it to the preparation of related drugs, not only has good solubility, fast drug release speed, but also high oral bioavailability. More than 90% is released in HCl with a pH of 1.2 for 20 minutes, and the oral bioavailability is increased by 225.19% compared with valsartan commercial capsules. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a result diagram of the in vitro release experiment of valsartan solid self-microemulsified resin in Test Example 1 of the present invention;

[0033] Figure 2 This is a comparison result diagram of the pharmacokinetic data of valsartan solid self-microemulsifying resin in SD rats according to Test Example 3 of the present invention. DETAILED DESCRIPTION

[0034] The present invention is further described below in conjunction with specific embodiments.

[0035] In the present invention, unless otherwise specified, percentages and percentage contents are all by mass. Unless otherwise specified, the experimental methods used are all conventional methods, and the materials and reagents used can be purchased from commercial sources.

[0036] Tables 1 and 2 list the main instruments and materials used in the examples.

[0037] Table 1 Experimental materials used in the examples

[0038]

[0039] Table 2 Experimental instruments used for testing the embodiment:

[0040]

[0041] Embodiment 1:

[0042] A valsartan solid self-microemulsifying resin drug delivery system, the preparation method is as follows:

[0043] (1) Preparation of valsartan liquid self-microemulsion: Weigh 1.9 g of Campul MCMC-8EP / NF, 6 g of Tween 80 and 2.1 g of diethylene glycol monoethyl ether (total weight 10 g), and place the mixture in a 37°C constant temperature water bath and stir at a stirring speed of 400 r / min. After stirring for 30 min, add 80 mg of valsartan and continue stirring for 1 h to obtain a transparent and clear valsartan liquid self-microemulsion.

[0044] (2) Crushing of macroporous ion exchange resin: Take an appropriate amount of macroporous ion exchange resin and add it to a multifunctional crusher and crush it for 30 minutes. After the crushing is completed, take it out and pass it through an 80-mesh sieve;

[0045] (3) Preparation of valsartan solid self-microemulsification resin: Weigh the above valsartan liquid self-microemulsion and place it in a round-bottom flask, add 10mL of anhydrous ethanol, add macroporous ion exchange resin in a ratio of 2:1, wrap the outside of the round-bottom flask with tin foil, and stir magnetically for 1 hour at room temperature to allow the valsartan liquid self-microemulsion to fully contact the macroporous ion exchange resin so that it can fully adsorb the valsartan liquid self-microemulsion. After mixing evenly, place the mixture on a vacuum rotary evaporator and slowly vacuum rotary evaporate under a 40°C water bath for 30 minutes. After the rotary evaporation is completed, gently scrape the solid self-microemulsion from the round-bottom flask with a medicine spoon and pass it through a 40-mesh sieve to obtain a valsartan solid self-microemulsification resin drug delivery system.

[0046] Embodiment 2:

[0047] A valsartan solid self-microemulsifying resin drug delivery system, the preparation method is as follows:

[0048] (1) Preparation of valsartan liquid self-microemulsion: Weigh 1.9 g of Campul MCMC-8EP / NF, 6 g of Tween 80 and 2.1 g of diethylene glycol monoethyl ether (total weight 10 g), and place the mixture in a 37°C constant temperature water bath and stir at a stirring speed of 400 r / min. After stirring for 30 min, add 160 mg of valsartan, and continue stirring for 1 h to obtain a transparent and clear valsartan liquid self-microemulsion;

[0049] (2) Crushing of macroporous ion exchange resin: Take an appropriate amount of macroporous ion exchange resin and add it to a multifunctional crusher and crush it for 30 minutes. After the crushing is completed, take it out and pass it through an 80-mesh sieve;

[0050] (3) Preparation of valsartan solid self-microemulsification resin: Weigh the above valsartan liquid self-microemulsion and place it in a round-bottom flask, add 10mL of anhydrous ethanol, add macroporous ion exchange resin in a ratio of 2:1, wrap the outside of the round-bottom flask with tin foil, and stir magnetically for 1 hour at room temperature to allow the valsartan liquid self-microemulsion to fully contact the macroporous ion exchange resin so that it can fully adsorb the valsartan liquid self-microemulsion. After mixing evenly, place the mixture on a vacuum rotary evaporator and slowly vacuum rotary evaporate under a 40°C water bath for 30 minutes. After the rotary evaporation is completed, gently scrape the solid self-microemulsion from the round-bottom flask with a medicine spoon and pass it through a 40-mesh sieve to obtain a valsartan solid self-microemulsification resin drug delivery system.

[0051] Embodiment 3:

[0052] A valsartan solid self-microemulsifying resin drug delivery system, the preparation method is as follows:

[0053] (1) Preparation of valsartan liquid self-microemulsion: Weigh 1.9 g of Campul MCMC-8EP / NF, 6 g of Tween 80 and 2.1 g of diethylene glycol monoethyl ether (total weight 10 g), and place the mixture in a 37°C constant temperature water bath and stir at a stirring speed of 400 r / min. After stirring for 30 min, add 80 mg of valsartan and continue stirring for 1 h to obtain a transparent and clear valsartan liquid self-microemulsion.

[0054] (2) Crushing of macroporous ion exchange resin: Take an appropriate amount of macroporous ion exchange resin and add it to a multifunctional crusher and crush it for 30 minutes. After the crushing is completed, take it out and pass it through an 80-mesh sieve;

[0055] (3) Preparation of valsartan solid self-microemulsification resin: Weigh the above valsartan liquid self-microemulsion and place it in a round-bottom flask, add 10mL of anhydrous ethanol, add macroporous ion exchange resin in a ratio of 1:1, wrap the outside of the round-bottom flask with tin foil, and stir magnetically at room temperature for 1 hour to allow the valsartan liquid self-microemulsion to fully contact the macroporous ion exchange resin so that it can fully adsorb the valsartan liquid self-microemulsion. After mixing evenly, place the mixture on a vacuum rotary evaporator and slowly vacuum rotary evaporate under a 40°C water bath for 30 minutes. After the rotary evaporation is completed, gently scrape the solid self-microemulsion from the round-bottom flask with a medicine spoon and pass it through a 40-mesh sieve to obtain a valsartan solid self-microemulsification resin drug delivery system.

[0056] Embodiment 4:

[0057] A valsartan solid self-microemulsifying resin drug delivery system, the preparation method is as follows:

[0058] (1) Preparation of valsartan liquid self-microemulsion: Weigh 1.9 g of Campul MCMC-8EP / NF, 6 g of Tween 80 and 2.1 g of diethylene glycol monoethyl ether (total weight 10 g), and place the mixture in a 37°C constant temperature water bath and stir at a stirring speed of 400 r / min. After stirring for 30 min, add 80 mg of valsartan and continue stirring for 1 h to obtain a transparent and clear valsartan liquid self-microemulsion.

[0059] (2) Crushing of macroporous ion exchange resin: Take an appropriate amount of macroporous ion exchange resin and add it to a multifunctional crusher and crush it for 30 minutes. After the crushing is completed, take it out and pass it through an 80-mesh sieve;

[0060] (3) Preparation of valsartan solid self-microemulsification resin: Weigh the above valsartan liquid self-microemulsion and place it in a round-bottom flask, add 10mL of anhydrous ethanol, add macroporous ion exchange resin in a ratio of 3:1, wrap the outside of the round-bottom flask with tin foil, and stir magnetically for 1 hour at room temperature to allow the valsartan liquid self-microemulsion to fully contact the macroporous ion exchange resin so that it can fully adsorb the valsartan liquid self-microemulsion. After mixing evenly, place the mixture on a vacuum rotary evaporator and slowly vacuum rotary evaporate under a 40°C water bath for 30 minutes. After the rotary evaporation is completed, gently scrape the solid self-microemulsion from the round-bottom flask with a medicine spoon and pass it through a 40-mesh sieve to obtain a valsartan solid self-microemulsification resin drug delivery system.

[0061] Comparative Example 1:

[0062] 900mLpH 1.2HCl is used as release medium, and valsartan commercial capsules and prepared valsartan solid self-microemulsifying resin are taken in appropriate amounts, and the speed is set to 50r / min, and the temperature is 37±0.5°C, and 5mL release medium is taken out (and an equal volume of fresh medium is supplemented) at different time intervals (5, 10, 15, 20, 30, 45, 60, 90, 120min). 0.45μm water filter membrane is filtered and then tested by HPLC system injection. The in vitro dissolution of valsartan solid self-microemulsifying resin in 30min is greater than 90%, and almost all dissolves in 2h, and the release rate and in vitro dissolution are much higher than those of valsartan commercial capsules.

[0063] Performance Test:

[0064] (I) Study on the particle size distribution of the valsartan solid self-microemulsified resin prepared in Example 1:

[0065] 0.1g of valsartan solid self-emulsifying resin was weighed and added to 100mL of distilled water at 37°C to form a microemulsion by self-emulsification. Since the valsartan solid self-emulsifying resin contains some water-insoluble macroporous ion exchange resin, it was centrifuged at 5000rpm for 10min and filtered through a 0.45μm microporous filter membrane. The particle size distribution was measured by a particle size analyzer. The results showed that the particle size of the valsartan solid self-emulsifying resin was 329.93±1.43nm and the PDI value was 0.104±0.006, indicating that the microemulsion had a uniform particle size distribution and good dispersibility; the Zeta potential was -20.14±1.04mV, indicating that the microemulsion had good stability.

[0066] (II) In vitro drug release experiment of valsartan solid self-microemulsification resin prepared in Example 1:

[0067] In vitro testing is an important means of screening prescriptions and determining processes, and it also plays an important role in the quality control of preparations, which is mainly investigated through dissolution rate. The present invention selects 900mL pH 1.2HCl as the release medium, takes an appropriate amount of valsartan commercially available capsules and the prepared valsartan solid self-microemulsification resin, sets the rotation speed to 50r / min, and the temperature to 37±0.5°C, and takes out 5mL of the release medium at different time intervals (5, 10, 15, 20, 30, 45, 60, 90, 120min) (and supplements with an equal volume of fresh medium). After filtering with a 0.45μm water filter membrane, the sample is injected and tested through an HPLC system to calculate the cumulative drug release of the valsartan commercially available capsules and the valsartan solid self-microemulsification resin. The drug release curve is drawn with the sampling time point as the X-axis and the cumulative dissolution as the Y-axis. The drug release curve is shown in Figure 1 .

[0068] (III) Pharmacokinetics experiment of valsartan solid self-microemulsifying resin prepared in Example 1

[0069] Animal model: SD rats were used as experimental animals. Group design: The rats were randomly divided into a homemade group and a commercially available group.

[0070] The self-made valsartan solid self-microemulsification resin and commercially available valsartan capsules (dosage: 10 mg / kg) were administered respectively, and the changes in blood drug concentrations over time were recorded.

[0071] Drug concentration determination method: High performance liquid chromatography (HPLC) was used to determine the blood concentration of valsartan.

[0072] Table 3 Pharmacokinetic comparison of commercially available valsartan capsules and valsartan solid self-microemulsified resin

[0073] parameter Valsartan commercial capsules Valsartan solid self-microemulsifying resin Tmax(h) 2 1 <![CDATA[C max (of mL) -1 )]]> 341.68 1660.53 <![CDATA[MRT 0-24 (h)]]> 7.99 9.41 <![CDATA[t 1 / 2 (h)]]> 25.99 36.44 <![CDATA[AUC 0-24 (ng·h·mL) -1 )]]> 2980.22 6711.16 <![CDATA[AUC 0-∞ (ng·h·mL) -1 )]]> 5880.83 14702.00 Fr(％) - 225.19

[0074] Please refer to the experimental results shown in Table 3: SD rat in vivo pharmacokinetic data, valsartan solid self-microemulsification resin Cmax, MRT, t1 / 2, AUC are higher than valsartan commercial capsules, indicating that the valsartan solid self-microemulsification resin prepared by the present invention can significantly improve the oral bioavailability of valsartan, compared with the commercial valsartan capsules, the oral bioavailability of valsartan solid self-microemulsification resin is increased by 225.19%, the specific data results are as follows Figure 2 shown.

[0075] The applicant declares that the present invention illustrates the process method of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned process steps, that is, it does not mean that the present invention must rely on the above-mentioned process steps to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials selected by the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0076] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0077] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A valsartan solid self-microemulsifying resin drug delivery system, characterized in that The self-microemulsion is prepared by a solid carrier adsorption method. The solid carrier is an ion exchange resin. The drug-carrying system also includes the following components for preparing a valsartan liquid self-microemulsion: valsartan, a liquid self-microemulsion oil phase, an emulsifier and an auxiliary emulsifier. The mass ratio of valsartan, the liquid self-microemulsion oil phase, the emulsifier and the auxiliary emulsifier is 1:1-2:3-5:1-2; and the mass ratio of the valsartan liquid self-microemulsion to the ion exchange resin is 1:1-3.

2. The valsartan solid self-microemulsifying resin drug delivery system according to claim 1, characterized in that: The ion exchange resin is a macroporous ion exchange resin.

3. The valsartan solid self-microemulsifying resin drug delivery system according to claim 1, characterized in that: The liquid self-microemulsified oil phase comprises any one of isopropyl myristate, Campul MCMC-8EP / NF monocaprylic glyceride, Labrafil M 2125 CS linoleoyl polyoxyethylene-6 glyceride or a combination of at least two thereof.

4. The valsartan solid self-microemulsifying resin drug delivery system according to claim 1, characterized in that: The emulsifier includes any one of Tween 20, Tween 80 and Span 80.

5. The valsartan solid self-microemulsifying resin drug delivery system according to claim 1, characterized in that: The auxiliary emulsifier is any one of diethylene glycol monoethyl ether, polyethylene glycol 400 (PEG400) or n-butanol.

6. A method for preparing a valsartan solid self-microemulsifying resin drug delivery system as claimed in any one of claims 1 to 5, characterized in that The steps include: S1. Preparation of valsartan liquid self-microemulsion: weigh the liquid self-microemulsion oil phase, emulsifier and co-emulsifier according to proportion and mix them evenly, place the mixture in a constant temperature water bath and stir to mix evenly, then add valsartan, and continue stirring until a transparent and clear valsartan liquid self-microemulsion is obtained; S2, pulverizing of ion exchange resin: take ion exchange resin and add it into a multifunctional pulverizer, after pulverizing, take it out and pass it through a 40-80 mesh sieve; S3, preparation of valsartan solid self-microemulsification resin: weigh the valsartan liquid self-microemulsification obtained in S1 and place it in a round-bottom flask, add anhydrous ethanol, add ion exchange resin, wrap the outside of the round-bottom flask with tin foil, and stir magnetically at room temperature to make the valsartan liquid self-microemulsification fully contact with the ion exchange resin so that the valsartan liquid self-microemulsification is fully adsorbed; S4. After mixing evenly, place the mixture on a vacuum rotary evaporator. Slowly perform vacuum rotary evaporation in a water bath. Use a medicine spoon to scrape the solid self-microemulsion from the round-bottom flask and pass it through a 40-80 mesh sieve to obtain the valsartan solid self-microemulsion resin drug delivery system.

7. The method for preparing the valsartan solid self-microemulsifying resin drug delivery system according to claim 6, characterized in that The steps include: S1. Preparation of valsartan liquid self-microemulsion: weigh the liquid self-microemulsion oil phase, emulsifier and co-emulsifier in proportion and mix them evenly, and place the mixture in a constant temperature water bath at 25-50° C. and stir at a stirring speed of 200-500 r / min. After stirring for 20-40 min, add valsartan, and continue stirring for 0.5-2 h to obtain a transparent and clear valsartan liquid self-microemulsion; S2. Grinding of ion exchange resin: add ion exchange resin to a multifunctional grinder and grind for 20-40 min. After grinding, take out and pass through a 40-80 mesh sieve; S3, preparation of valsartan solid self-microemulsification resin: weigh S1 to obtain valsartan liquid self-microemulsification, place it in a round-bottom flask, add 10-20 mL of anhydrous ethanol, add ion exchange resin in a ratio of 2:1-4:1, wrap the outside of the round-bottom flask with tin foil, and stir magnetically at room temperature for 0.5-1.5 h to allow the valsartan liquid self-microemulsification to fully contact the ion exchange resin so that the valsartan liquid self-microemulsification is fully adsorbed; S4. After mixing evenly, place the mixture on a vacuum rotary evaporator and slowly perform vacuum rotary evaporation in a water bath at 35-45°C for 20-40 minutes. After the rotary evaporation is completed, gently scrape the solid self-microemulsion from the round-bottom flask with a medicine spoon and pass it through a 40-80 mesh sieve to obtain the valsartan solid self-microemulsion resin drug delivery system.

8. Use of the valsartan solid self-microemulsifying resin drug delivery system according to any one of claims 1 to 5 in the preparation of hypertension drugs.

9. An application of the valsartan solid self-microemulsifying resin drug delivery system as claimed in any one of claims 1 to 5, characterized in that Fill into capsule shells to make capsules or compress into tablets.

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