Andrographolide pharmaceutical composition and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical compositions, in particular to an andrographolide pharmaceutical composition and a preparation method thereof. The andrographolide pharmaceutical composition consists of the following components in parts by weight: 2-4 parts of a composite solid dispersion, 2-4 parts of an absorption enhancer, 1-2 parts of a filling agent, 0.1-0.2 part of a disintegrating agent and 0.02-0.04 part of a lubricating agent, wherein the composite solid dispersion comprises andrographolide-phospholipid solid particles and a solid dispersion carrier, the andrographolide-phospholipid solid particles comprise andrographolide and a phospholipid carrier, and the mass ratio of the andrographolide to the phospholipid carrier to the solid dispersion carrier is 1: (0.8-1.2): (2.3-2.7). The andrographolide pharmaceutical composition provided by the invention achieves the optimized effect of simultaneously improving the water solubility and fat solubility of the medicine, and the in-vivo absorption is further improved.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical compositions, and particularly relates to an andrographolide pharmaceutical composition and a preparation method thereof. Background Art

[0002] Andrographolide (AD) is one of the main active ingredients of the commonly used Chinese herbal medicine Andrographis paniculata, and has the effects of clearing heat and detoxifying, anti-inflammatory, detumescence and pain relief. In recent years, more and more pharmacological studies on andrographolide have shown that it has the effects of anti-inflammatory, antibacterial, antiviral, protecting the liver and gallbladder, immunomodulating, anti-tumor, etc. The marketed preparations of andrographolide and its derivatives include andrographolide tablets, andrographolide dripping pills, potassium dehydroandrographolide succinate injection, virus static eye drops and compound potassium dehydroandrographolide succinate coating agents, etc., all of which have good anti-inflammatory, antibacterial, antiviral and other effects.

[0003] Andrographolide is a white crystalline compound of diterpene lactone type, bitter in taste, soluble in boiling ethanol, slightly soluble in methanol or ethanol, very slightly soluble in chloroform, and almost insoluble in water or ether. It is a drug that is poorly soluble in both water and lipids. For oral administration, the water solubility and permeability of the drug are two main factors limiting the absorption of the gastrointestinal mucosa. Studies have shown that the solubility of andrographolide in water is only 65 μg / ml, and the oil-water partition coefficient logP is about 0.5 (n-octanol-water partition system). Oral administration is predicted to result in poor absorption in vivo. Animal studies in vivo have shown that the oral bioavailability is only 0.98%. Therefore, there are problems such as a large dosage, unclear drug efficacy, and at the same time, due to poor absorption in vivo, a large amount of the drug is taken, and patients often feel stomach discomfort due to the extremely bitter taste. The currently marketed andrographolide dripping pills use polyethylene glycol as a solid dispersion auxiliary material. The andrographolide raw material is highly dispersed in polyethylene glycol to improve the hydrophilicity. For the anti-inflammatory treatment of sore throat, the daily dosage is relatively large, 150 mg / bag, and 3 bags are taken daily. Therefore, how to improve the solubility of andrographolide and enhance the absorption in vivo has become a key technical problem.

[0004] Currently, the preparation of solid dispersions of andrographolide by hot melt extrusion has become a research hotspot. Although it has shown a certain effect on the absorption of andrographolide in vivo, for the properties of poor water solubility and lipid solubility of andrographolide, the improvement of the water solubility of andrographolide by solid dispersion is far from enough to improve the absorption in vivo. How to further improve the permeability to enhance the absorption in vivo on the basis of solving the above problems is also a difficult problem faced by this field.

[0005] Based on this, the present invention provides an andrographolide pharmaceutical composition and a preparation method thereof to improve the water solubility, lipid solubility and permeability of the drug. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide an andrographolide pharmaceutical composition and a preparation method thereof.

[0007] To solve the above problems, the technical solution adopted by the present invention is as follows: In the first aspect, a andrographolide pharmaceutical composition is provided, which is composed of the following components in parts by weight: 2 - 4 parts of a composite solid dispersion, 2 - 4 parts of an absorption promoter, 1 - 2 parts of a filler, 0.1 - 0.2 parts of a disintegrant, and 0.02 - 0.04 parts of a lubricant; Among them, the composite solid dispersion includes andrographolide - phospholipid solid particles and a solid dispersion carrier. The andrographolide - phospholipid solid particles include andrographolide and a phospholipid carrier. The mass ratio of andrographolide, the phospholipid carrier, and the solid dispersion carrier is 1:(0.8 - 1.2):(2.3 - 2.7).

[0008] As an embodiment of the present invention, the phospholipid - based lipophilic carrier is selected from at least one of soybean phospholipid, egg yolk lecithin, hydrogenated soybean phospholipid, and polyene phosphatidylcholine.

[0009] As an embodiment of the present invention, the water - soluble solid dispersion carrier is selected from at least one of copovidone, soluplus, polyvinyl alcohol, and hypromellose acetate succinate.

[0010] As an embodiment of the present invention, the absorption promoter is sodium 8 - (2 - hydroxybenzamido) octanoate (Salcaprozate sodium, SNAC).

[0011] As an embodiment of the present invention, the filler is selected from at least one of microcrystalline cellulose, corn starch, calcium hydrogen phosphate, and lactose; the disintegrant is selected from at least one of croscarmellose sodium, crospovidone, and sodium carboxymethyl starch; the lubricant is selected from at least one of calcium stearate, sodium stearyl fumarate, and stearic acid.

[0012] As an embodiment of the present invention, the composite solid dispersion is obtained by the following method: (1) Dissolve the phospholipid carrier in heated ethanol to form a clear solution. Then, evenly spray the clear solution onto andrographolide to granulate and mix to obtain andrographolide - phospholipid solid particles; (2) Add the andrographolide - phospholipid solid particles and the solid dispersion carrier into a twin - screw hot - melt extruder, and after melting and homogenizing, obtain a clear, transparent, uniform, light - yellow fine - strip extrudate, which is the composite solid dispersion.

[0013] As an embodiment of the present invention, the temperature of the feeding section of the twin-screw hot melt extruder is controlled at 90-120 °C (specifically, it can be 90 °C, 100 °C, 110 °C or 120 °C); the temperature of the melting section is controlled at 190 °C - 210 °C (specifically, it can be 190 °C, 200 °C or 210 °C); the screw speed of the twin-screw hot melt extruder is 200-400 rpm. Multiple regions can be set in the feeding section and the melting section as needed. Exemplarily, 2 feeding regions are set in the feeding section, and 6 melting regions are set in the melting section. The temperatures of the 2 feeding regions are 90 °C and 120 °C respectively; the temperatures of the 6 melting regions are all 200 °C.

[0014] In a second aspect, a preparation method of the andrographolide pharmaceutical composition according to the first aspect is provided, and the method includes: Step S1: Crush the composite solid dispersion with a pulverizer and pass through a 30-80 mesh sieve to obtain the particles under the sieve; Step S2: Mix the particles under the sieve with an absorption promoter, a filler, a disintegrant and a lubricant evenly in a mixer, and then add the mixture into a tableting machine for tableting to obtain the andrographolide pharmaceutical composition.

[0015] As an embodiment of the present invention, in step S2, the rotation speed of the mixer is 8-12 rpm, and the mixing time is 12-18 min; As an embodiment of the present invention, in step S2, the hardness of the tablet core is 70-120 N.

[0016] The beneficial effects produced by adopting the above technical solutions are as follows: (1) The present invention first prepares a composite solid dispersion by hot melt extrusion of andrographolide, phospholipid carriers and solid dispersion carriers, and then combines with other excipients (absorption promoter, filler, disintegrant and lubricant) to improve the water solubility, lipid solubility and permeability of the drug simultaneously.

[0017] (2) The preparation method of the andrographolide pharmaceutical composition of the present invention adopts the hot melt extrusion technology, which has the advantages of no organic solvents, no dust, continuous operation and good reproducibility. This preparation process is simple and easy to operate.

[0018] (3) The andrographolide pharmaceutical composition provided by the present invention achieves the optimized effect of improving the water solubility and lipid solubility of the drug simultaneously. At 37 °C, the solubility in water can be as high as 859.3 μg / ml in 5 min, and can still be as high as 1201.4 μg / ml in 60 min; at 37 °C, the solubility in n-octanol is as high as 2055.7 μg / ml in 60 min; in addition, compared with the marketed preparation andrographolide dropping pills, the in vivo absorption of the present invention has been further improved. Description of the Drawings

[0019] Figure 1 These are the pharmacokinetic curves of the drugs in canine plasma after oral administration of different andrographolide drug compositions. Detailed implementation manners

[0020] To make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be clearly and completely described below in conjunction with specific embodiments. For those conditions not specified in the embodiments, they shall be carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments whose manufacturers are not specified, they are all conventional products that can be obtained through commercial purchase.

[0021] In the present invention, the raw material andrographolide (C 20 H 30 O5, relative molecular mass 350.45) has the following structural formula: Preparation Example 1 In this preparation example, a composite solid dispersion was prepared, which consisted of the following components: 50 g of andrographolide, 40 g of phospholipid carrier, and 115 g of solid dispersion carrier.

[0022] Among them, the phospholipid carrier was egg yolk lecithin, and the solid dispersion carrier was soluplus.

[0023] Its preparation method includes: (1) Dissolve the phospholipid carrier in heated ethanol to form a clear solution, and then evenly spray the clear solution onto andrographolide to granulate and mix to obtain andrographolide-phospholipid solid particles; (2) Add the andrographolide-phospholipid solid particles and the solid dispersion carrier to a twin-screw hot melt extruder, and after melting and homogenizing, obtain a clear, transparent, uniform, light yellow thin strip extrudate, which is the composite solid dispersion; among them, the temperature of the feeding section of the twin-screw hot melt extruder is controlled at 90-120 °C; the temperature of the melting section is controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extruder is 200 rpm.

[0024] Preparation Example 2 In this preparation example, a composite solid dispersion was prepared, which consisted of the following components: 50 g of andrographolide, 50 g of phospholipid carrier, and 125 g of solid dispersion carrier.

[0025] Among them, the phospholipid carrier was soy lecithin, and the solid dispersion carrier was copovidone.

[0026] Its preparation method includes: (1) Dissolve the phospholipid carrier in heated ethanol to form a clear solution. Then, evenly spray the clear solution onto andrographolide for granulation and mixing to obtain andrographolide-phospholipid solid particles. (2) Add the andrographolide-phospholipid solid particles and the solid dispersion carrier into a twin-screw hot melt extruder. After melting and homogenization, a clear, transparent, uniform light yellow thin strip extrudate is obtained, which is the composite solid dispersion. Among them, the feeding section temperature of the twin-screw hot melt extruder is controlled at 90 - 120 °C; the melting section temperature is controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extruder is 300 rpm.

[0027] Preparation Example 3 This preparation example prepared a composite solid dispersion, which consists of the following components: 50 g of andrographolide, 60 g of phospholipid carrier, and 135 g of solid dispersion carrier.

[0028] Among them, the phospholipid carrier is polyene phosphatidylcholine, and the solid dispersion carrier is polyvinyl alcohol.

[0029] Its preparation method includes: (1) Dissolve the phospholipid carrier in heated ethanol to form a clear solution. Then, evenly spray the clear solution onto andrographolide for granulation and mixing to obtain andrographolide-phospholipid solid particles. (2) Add the andrographolide-phospholipid solid particles and the solid dispersion carrier into a twin-screw hot melt extruder. After melting and homogenization, a clear, transparent, uniform light yellow thin strip extrudate is obtained, which is the composite solid dispersion. Among them, the feeding section temperature of the twin-screw hot melt extruder is controlled at 90 - 120 °C; the melting section temperature is controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extruder is 400 rpm.

[0030] Comparative Preparation Example 1 This comparative preparation example prepared a composite solid dispersion, which consists of the following components: 50 g of andrographolide and 100 g of copovidone (solid dispersion carrier).

[0031] Its preparation method includes: Add andrographolide and the solid dispersion carrier (copovidone) into a twin-screw hot melt extruder. After melting and homogenization, a clear, transparent, uniform light yellow thin strip extrudate is obtained, which is the composite solid dispersion. Among them, the feeding section temperature of the twin-screw hot melt extruder is controlled at 90 - 120 °C; the melting section temperature is controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extruder is 300 rpm.

[0032] Comparative Preparation Example 2 This comparative preparation example prepared a composite solid dispersion, which consisted of the following components: 50 g of andrographolide and 125 g of copovidone (solid dispersion carrier).

[0033] Its preparation method included: Adding andrographolide and the solid dispersion carrier (copovidone) into a twin-screw hot melt extrusion machine, after melting and homogenizing, a clear, transparent, uniform light yellow thin strip extrudate was obtained, which was the composite solid dispersion; among them, the feeding section temperature of the twin-screw hot melt extrusion machine was controlled at 90-120 °C; the melting section temperature was controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extrusion machine was 300 rpm.

[0034] Comparative Preparation Example 3 This comparative preparation example prepared a composite solid dispersion, which consisted of the following components: 50 g of andrographolide and 150 g of copovidone (solid dispersion carrier).

[0035] Its preparation method included: Adding andrographolide and the solid dispersion carrier (copovidone) into a twin-screw hot melt extrusion machine, after melting and homogenizing, a clear, transparent, uniform light yellow thin strip extrudate was obtained, which was the composite solid dispersion; among them, the feeding section temperature of the twin-screw hot melt extrusion machine was controlled at 90-120 °C; the melting section temperature was controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extrusion machine was 300 rpm.

[0036] Comparative Preparation Example 4 This preparation example prepared a composite solid dispersion, which consisted of the following components: 50 g of andrographolide, 50 g of phospholipid carrier, and 150 g of solid dispersion carrier.

[0037] Among them, the phospholipid carrier was soy lecithin, and the solid dispersion carrier was copovidone.

[0038] Its preparation method included: (1) Dissolving the phospholipid carrier in heated ethanol to form a clear solution, and then evenly spraying the clear solution onto andrographolide to granulate and mix, obtaining andrographolide-phospholipid solid particles; (2) Adding the andrographolide-phospholipid solid particles and the solid dispersion carrier into a twin-screw hot melt extrusion machine, after melting and homogenizing, a clear, transparent, uniform light yellow thin strip extrudate was obtained, which was the composite solid dispersion; among them, the feeding section temperature of the twin-screw hot melt extrusion machine was controlled at 90-120 °C; the melting section temperature was controlled at 190 °C - 210 °C; the screw speed of the twin-screw hot melt extrusion machine was 300 rpm.

[0039] Preparation Test Example 1 Andrographolide, commercially available andrographolide dripping pills (Tianjin Tasly Pharmaceutical Co., Ltd.), the composite solid dispersions prepared in Preparation Examples 1-3, and Comparative Preparation Examples 1-4 were separately taken, and the solubility in water was detected by the following method: The raw material andrographolide (raw material), commercially available andrographolide dripping pills, and all the composite solid dispersions were ground and put into a conical flask; the solubility in purified water was measured using a constant temperature oscillator at 37 °C, in parallel three portions. Samples were taken at different times and filtered through a 0.45 μm filter membrane. The samples were diluted, and the absorbance of the solution was measured at a wavelength of 224 nm according to the ultraviolet-visible spectrophotometry (General Principles 0401, Volume IV, Chinese Pharmacopoeia 2020 Edition), and the solubility was calculated according to the dilution factor. The results are shown in Table 1.

[0040] Table 1 Results of solubility test in water As can be seen from Table 1, the solubility of andrographolide (raw material) in water is extremely poor, insoluble in the first 20 minutes, and only 68.0 μg / mL after 60 minutes; the solubility of andrographolide dripping pills after 60 minutes is only 93.2 μg / mL; the solubility in Comparative Preparation Examples 1, 2, and 3 gradually increases, and the solubility of Preparation Example 2, Comparative Preparation Example 3, and Comparative Preparation Example 4 is not much different.

[0041] Preparation Test Example 2 Andrographolide (raw material), commercially available andrographolide dripping pills (Tianjin Tasly Pharmaceutical Co., Ltd.), the composite solid dispersion prepared in Preparation Example 2, and Comparative Preparation Examples 2 and 4 were separately taken, and the solubility in n-octanol was detected. The detection method was the same as that in Preparation Test Example 1, and the results are shown in Table 2.

[0042] Table 2 Results of solubility test in n-octanol As can be seen from Table 2, at 60 minutes, the solubility of andrographolide (raw material), andrographolide dripping pills, Comparative Preparation Example 2, and Comparative Preparation Example 3 is not much different; the solubility of Preparation Example 2 is the highest, and compared with it, the solubility of Comparative Preparation Example 4 decreases.

[0043] Example 1 An andrographolide pharmaceutical composition, which consists of the following components: 2 parts of the composite solid dispersion prepared in Preparation Example 2, 2 parts of the absorption promoter SNAC, 1 part of a filler, 0.1 part of a disintegrant, and 0.02 part of a lubricant. Among them, the filler is calcium hydrogen phosphate, the disintegrant is crospovidone, and the lubricant is calcium stearate.

[0044] Its preparation method includes: Step S1: Crush the composite solid dispersion prepared in Preparation Example 2 with a pulverizer, and pass through a 30-mesh sieve to obtain the particles under the sieve. Step S2: Mix the particles under the sieve obtained in Step S1 with an absorption promoter, a filler, a disintegrant, and a lubricant evenly in a mixer, and then add the mixture into a tableting machine for tableting to obtain the said andrographolide pharmaceutical composition; wherein, the rotation speed of the mixer is 8 rpm, the mixing time is 18 min; the hardness of the tablet core is 70 N.

[0045] Example 2 An andrographolide pharmaceutical composition, which is composed of the following components: 3 parts of the composite solid dispersion prepared in Preparation Example 2, 3 parts of the absorption promoter SNAC, 1.57 parts of a filler, 0.15 parts of a disintegrant, and 0.03 parts of a lubricant. Among them, the filler is a mixture of lactose and microcrystalline cellulose, the disintegrant is cross-linked carboxymethylcellulose sodium, and the lubricant is sodium stearyl fumarate.

[0046] Its preparation method includes: Step S1: Crush the composite solid dispersion prepared in Preparation Example 2 with a pulverizer, and pass through a 50-mesh sieve to obtain the particles under the sieve. Step S2: Mix the particles under the sieve obtained in Step S1 with an absorption promoter, a filler, a disintegrant, and a lubricant evenly in a mixer, and then add the mixture into a tableting machine for tableting to obtain the said andrographolide pharmaceutical composition; wherein, the rotation speed of the mixer is 10 rpm, the mixing time is 15 min; the hardness of the tablet core is 90 N.

[0047] Example 3 An andrographolide pharmaceutical composition, which is composed of the following components: 4 parts of the composite solid dispersion prepared in Preparation Example 2, 4 parts of the absorption promoter SNAC, 2 parts of a filler, 0.2 parts of a disintegrant, and 0.04 parts of a lubricant. Among them, the filler is corn starch, the disintegrant is carboxymethyl starch sodium, and the lubricant is stearic acid.

[0048] Its preparation method includes: Step S1: Crush the composite solid dispersion prepared in Preparation Example 2 with a pulverizer, and pass through a 50-mesh sieve to obtain the particles under the sieve. Step S2: Mix the particles under the sieve obtained in Step S1 with an absorption promoter, a filler, a disintegrant, and a lubricant evenly in a mixer, and then add the mixture into a tableting machine for tableting to obtain the said andrographolide pharmaceutical composition; wherein, the rotation speed of the mixer is 12 rpm, the mixing time is 12 min, and the hardness of the tablet core is 120 N.

[0049] Comparative Example 1 An andrographolide pharmaceutical composition, which is composed of the following components: 3 parts of the composite solid dispersion prepared in Preparation Example 2, 1.57 parts of a filler, 0.15 parts of a disintegrant, and 0.03 parts of a lubricant. Among them, the filler is a mixture of lactose and microcrystalline cellulose, the disintegrant is cross-linked carboxymethylcellulose sodium, and the lubricant is sodium stearyl fumarate.

[0050] Its preparation method includes: Step S1: Crush the composite solid dispersion prepared in Preparation Example 2 with a pulverizer and pass through a 50-mesh sieve to obtain the particles under the sieve; Step S2: Mix the particles under the sieve obtained in Step S1 with the filler, disintegrant, and lubricant evenly in a mixer to obtain the andrographolide pharmaceutical composition. The rotation speed of the mixer is 10 rpm, and the mixing time is 15 min.

[0051] Test example: This test example studies the single oral administration of commercially available andrographolide dropping pills, the self-made andrographolide drug of the present invention, and the andrographolide drug of the comparative example to beagle dogs, detects the blood drug concentration in the plasma, and evaluates its pharmacokinetic (PK) characteristics in beagle dogs.

[0052] Experimental materials: Male beagle dogs (body weight 6 - 10 kg), commercially available andrographolide dropping pills (Tianjin Tasly Pharmaceutical Co., Ltd.), andrographolide pharmaceutical composition A prepared in Example 2, andrographolide pharmaceutical composition B prepared in Comparative Example 1.

[0053] Experimental method: Randomly divide male beagle dogs into 3 groups (3 dogs in each group). The experimental group is given andrographolide pharmaceutical composition A, the control group 1 is given commercially available andrographolide dropping pills, and the control group 2 is given andrographolide pharmaceutical composition B. During the experiment, the dogs are allowed to drink water freely, fast overnight, and are given 110 g of feed half an hour before dosing. Administer the drug by oral gavage, and the dose given to each beagle dog is 15 mg / kg (calculated based on the amount of andrographolide).

[0054] Blood is taken at 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, and 24 h after dosing. After precipitating proteins with methanol, the supernatant is separated. The blood drug concentration is determined by LC / MS / MS method, and the data is statistically calculated using DAS software to evaluate its pharmacokinetic (PK) characteristics in beagle dogs. The data is shown in Table 3, and the pharmacokinetic curve is shown in Figure 1 .

[0055] Table 3 Pharmacokinetic parameters As can be seen from Table 3, compared with the commercially available Andrographolide Pills, the in vivo absorption of Andrographolide Pharmaceutical Composition B increased by about 2.9 times; on this basis, after adding the absorption enhancer SNAC, the AUC further increased by about 2.3 times compared with Andrographolide Pharmaceutical Composition B.

[0056] Therefore, the andrographolide pharmaceutical composition provided by the present invention, by mixing the poorly soluble drug andrographolide with a phospholipid carrier, a solid dispersion carrier, and an absorption enhancer SNAC in a predetermined ratio, not only effectively improves the solubility and permeability of the drug, but also significantly improves the in vivo absorption degree of andrographolide, increases the drug exposure in vivo, and effectively ensures the exertion of the drug efficacy in vivo.

[0057] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A andrographolide pharmaceutical composition, characterized in that, It is composed of the following components in parts by weight: 2 - 4 parts of compound solid dispersion, 2 - 4 parts of absorption promoter, 1 - 2 parts of filler, 0.1 - 0.2 parts of disintegrant, 0.02 - 0.04 parts of lubricant; Among them, the compound solid dispersion includes andrographolide - phospholipid solid particles and a solid dispersion carrier. The andrographolide - phospholipid solid particles include andrographolide and a phospholipid carrier. The mass ratio of andrographolide, the phospholipid carrier and the solid dispersion carrier is 1:(0.8 - 1.2):(2.3 - 2.7).

2. The andrographolide pharmaceutical composition according to claim 1, characterized in that, The phospholipid carrier is selected from at least one of soybean phospholipid, egg yolk lecithin, hydrogenated soybean phospholipid, polyene phosphatidylcholine.

3. The andrographolide pharmaceutical composition according to claim 1, wherein The solid dispersion carrier is selected from at least one of copovidone, soluplus, polyvinyl alcohol, hypromellose acetate succinate.

4. The andrographolide pharmaceutical composition according to claim 1, characterized in that, The absorption promoter is sodium 8-(2 - hydroxybenzamido)octanoate.

5. The andrographolide pharmaceutical composition according to claim 1, characterized in that, The filler is selected from at least one of microcrystalline cellulose, corn starch, calcium hydrogen phosphate, lactose; the disintegrant is selected from at least one of croscarmellose sodium, crospovidone, sodium carboxymethyl starch; the lubricant is selected from at least one of calcium stearate, sodium stearyl fumarate, stearic acid.

6. The andrographolide pharmaceutical composition according to claim 1, wherein The compound solid dispersion is obtained by the following method: (1) Dissolve the phospholipid carrier in heated ethanol to form a clear solution. Then, evenly spray the clear solution onto andrographolide to granulate and mix evenly to obtain andrographolide - phospholipid solid particles; (2) Add the andrographolide - phospholipid solid particles and the solid dispersion carrier into a twin - screw hot - melt extruder. After melting and homogenizing, a clear, transparent, uniform light - yellow fine - strip extrudate is obtained, which is the compound solid dispersion.

7. The andrographolide pharmaceutical composition according to claim 6, wherein, In step (2), the temperature of the feeding section of the twin - screw hot - melt extruder is controlled at 90 - 120°C; the temperature of the melting section is controlled at 190 - 210°C; the screw speed of the twin - screw hot - melt extruder is 200 - 400 rpm.

8. A preparation method of an andrographolide pharmaceutical composition according to any one of claims 1 to 7, characterized in that, The method includes: Step S1: Crush the compound solid dispersion with a pulverizer and pass through a 30 - 80 - mesh sieve to obtain the particles under the sieve; Step S2: Uniformly mix the particles under the sieve with the absorption promoter, filler, disintegrant and lubricant in a mixer, and then add the mixture into a tableting machine to press tablets to obtain the andrographolide pharmaceutical composition.

9. The preparation method of an andrographolide pharmaceutical composition according to claim 8, characterized in that, In step S2, the rotation speed of the mixer is 8 - 12 rpm, and the mixing time is 12 - 18 min.

10. The preparation method of an andrographolide pharmaceutical composition according to claim 8, wherein, In step S2, the hardness of the tablet core is 70 - 120 N.

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