Compound red sage root tablet and preparation method thereof

Abstract

The invention provides a compound salvia miltiorrhiza tablet and a preparation method thereof. The preparation method comprises the following steps: (1) weighing the following raw materials: 450g of salvia miltiorrhiza, 141 g of pseudo-ginseng and 8g of borneol; (2) crushing radix salviae miltiorrhizae to 30-60 meshes, adding 10-12 times of water, adding a compound enzyme consisting of cellulase, pectinase and neutral protease, adjusting the pH value to 3.5-4, extracting at 35-42 DEG C for 4-8 hours, filtering to obtain a filtrate, and concentrating the filtrate to obtain an extract A; (3) crushing pseudo-ginseng to 80-100 meshes to obtain pseudo-ginseng coarse powder, extracting and filtering to obtain filtrate, and concentrating the filtrate to obtain extract B; (3) mixing the extract A and the extract B with auxiliary materials to prepare particles, and drying; and (4) grinding borneol, uniformly mixing with the granules, pressing into tablets, and coating with a film to obtain the compound salvia tablets. According to the preparation method, the extraction rate of effective components is increased, and the complete disintegration time of the salvia tablets is shortened.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and particularly relates to a compound danshen tablet and a preparation method thereof. Background Art

[0002] Compound Danshen Tablets (containing Danshen, Panax notoginseng, and borneol) are Chinese patent medicines that promote blood circulation, remove blood stasis, regulate qi, and relieve pain. Danshen has the effects of dilating coronary arteries, increasing coronary blood flow, slowing heart rate, and improving myocardial hypoxia. It is often used to treat coronary heart disease, angina pectoris, chest tightness, palpitations, and can also treat myocardial infarction and myocarditis, and can improve acute symptoms and ischemic changes in the electrocardiogram. Danshen can dredge the meridians and nourish the blood, promote blood circulation, remove blood stasis, regulate menstruation, and therefore can treat women's menstrual disorders, amenorrhea, abdominal pain caused by postpartum stasis, and limb pain. Due to its reliable efficacy, small side effects, and low price, Compound Danshen Tablets have become one of the most frequently used Chinese patent medicines.

[0003] Compound Danshen Tablet is a commonly used Chinese patent medicine, the main ingredients of which include Danshen, Panax notoginseng and borneol. Its main effects include promoting blood circulation and removing blood stasis, regulating qi and relieving pain. It is often used to treat discomfort symptoms caused by qi stagnation and blood stasis, such as chest tightness, stabbing pain in the precordial area, chest pain and other symptoms. The specific effects and functions of Compound Danshen Tablet include but are not limited to: Promoting blood circulation and removing blood stasis: It can promote blood circulation and eliminate blood stasis. Regulating qi and relieving pain: It can relieve qi blockage and relieve pain. Dilate blood vessels: It can dilate coronary arteries and increase coronary blood flow. Regulate blood lipids: It helps to improve dyslipidemia. Improve microcirculation: It helps to improve blood circulation in local tissues. Anti-inflammatory effect: It has a certain anti-inflammatory effect. Antioxidant effect: It can scavenge free radicals and protect myocardial cells.

[0004] Since there is a concentration gradient of the active ingredients in the extraction tank in the existing hot reflux extraction technology, the active ingredients in the compound danshen tablets automatically migrate from high concentration to low concentration, which reduces the extraction efficiency and makes it impossible to guarantee the quality of the product. Summary of the invention

[0005] The purpose of the invention is to provide a compound danshen tablet and a preparation method thereof.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A method for preparing a compound danshen tablet comprises the following steps:

[0008] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0009] (2) Crush the salvia miltiorrhiza to 30-60 mesh, add 10-12 times the amount of water, add a complex enzyme consisting of cellulase, pectinase and neutral protease, adjust the pH to 3.5-4, extract at 35°C-42°C for 4-8 hours, filter to obtain a filtrate, and concentrate the filtrate to obtain extract A;

[0010] (3) Grind Panax notoginseng into 80-100 mesh to obtain Panax notoginseng coarse powder, add 6-10 times amount of water, adjust the pH value to 5.5-6.5 with HCl, heat to 100°C and extract for 1.5h-3h; then adjust the pH value to 7-9 with NaOH, extract at 100°C for 1.5h-3h, filter to obtain the filtrate, and concentrate the filtrate to obtain extract B;

[0011] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0012] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0013] Furthermore, the weight ratio of cellulase, pectinase and neutral protease is (2-3):1:(0.3-0.7).

[0014] Furthermore, the mass fraction of the complex enzyme in water is 1% to 3%.

[0015] Furthermore, the auxiliary materials include one or more of fillers, disintegrants, stabilizers, and lubricants.

[0016] Furthermore, the auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of (0.3-0.5):(0.9-1.3):(0.1-0.5):1.

[0017] Furthermore, the ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.2-1.5:1.

[0018] Furthermore, the filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:(1.3-1.5):(0.2-0.4).

[0019] Furthermore, the stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.3-1.5.

[0020] Furthermore, the disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.2-0.5:1:1.4-1.7.

[0021] Furthermore, the preparation method of the modified starch is:

[0022] (1) Mixing starch and water in a mass ratio of 1 to 2:10 to obtain starch milk;

[0023] (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 15 to 25 minutes, heating to 45 to 55° C. and keeping the temperature for reaction for 12 to 16 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch;

[0024] (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 15 to 20 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch;

[0025] (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

[0026] Furthermore, the amount of sodium hydroxide added is 1% to 4% of the dry weight of starch.

[0027] Furthermore, the amount of propylene oxide added is 10% to 15% of the dry basis mass of starch.

[0028] Furthermore, the starch is corn starch. Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0029] Furthermore, the amount of hexadecenylsuccinic anhydride added is 12-17% of the dry weight of starch.

[0030] Furthermore, the lubricant is selected from one or more of sodium stearyl fumarate, micro powder silica gel, and magnesium stearate.

[0031] The invention also provides compound danshen tablets prepared by the preparation method.

[0032] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows: The present invention uses cellulase, pectinase and neutral protease: these enzymes can degrade cellulose, pectin and other structural components in plant cell walls, thereby increasing the dissolution rate of effective ingredients. Composite enzymes are used in the extraction process of Salvia miltiorrhiza: through the action of enzymes, complex substances in Salvia miltiorrhiza can be effectively decomposed, making it easier to extract effective ingredients such as Tanshinone ⅡA. Two-stage pH value regulation in the extraction process of Panax notoginseng: first, the pH value is adjusted to 5.5 with HCl, which helps to extract specific effective ingredients; then the pH value is adjusted to 7 with NaOH to further extract other effective ingredients. This two-stage pH value regulation helps to maximize the extraction of effective ingredients in Panax notoginseng. Extraction at 100℃ for 1.5h: high temperature conditions help to accelerate the dissolution of effective ingredients, and also help to improve extraction efficiency. At the same time, adding modified starch to the disintegrant of the present invention can reduce the time it takes for the Salvia miltiorrhiza tablets to completely disintegrate. DETAILED DESCRIPTION

[0033] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Example 1

[0035] This embodiment provides a method for preparing a compound Danshen tablet, comprising the following steps:

[0036] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0037] (2) crushing Danshen into 60 mesh, adding 12 times the amount of water, adding a complex enzyme consisting of cellulase, pectinase and neutral protease, adjusting the pH to 4, extracting at 42°C for 8 h, filtering the filtrate, and concentrating the filtrate to obtain extract A;

[0038] (3) Grind Panax notoginseng into 100 mesh to obtain Panax notoginseng coarse powder, add 10 times the amount of water, adjust the pH value to 6.5 with HCl, heat to 100°C and extract for 3 hours; then adjust the pH value to 9 with NaOH, extract at 100°C for 3 hours, filter the filtrate, and concentrate the filtrate to obtain extract B;

[0039] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0040] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0041] The weight ratio of cellulase, pectinase and neutral protease is 3:1:0.7.

[0042] The mass fraction of the complex enzyme in water is 3%.

[0043] The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of 0.5:1.3:0.5:1.

[0044] The ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.5:1.

[0045] The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:1.5:0.4.

[0046] The stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.5.

[0047] The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.5:1:1.7.

[0048] The preparation method of the modified starch is:

[0049] (1) Mixing starch and water in a mass ratio of 1:5 to obtain starch milk;

[0050] (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 25 minutes, heating to 55° C. and keeping the temperature for 16 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch;

[0051] (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 20 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch;

[0052] (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

[0053] The amount of sodium hydroxide added is 4% of the dry weight of starch.

[0054] The added amount of propylene oxide is 15% of the dry basis mass of starch.

[0055] The starch is corn starch. Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0056] The added amount of hexadecenylsuccinic anhydride is 17% of the dry basis weight of starch.

[0057] The lubricant is sodium stearyl fumarate.

[0058] Example 2

[0059] This embodiment provides a method for preparing a compound Danshen tablet, comprising the following steps:

[0060] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0061] (2) Crush the salvia miltiorrhiza to 30 mesh, add 10 times the amount of water, add a complex enzyme consisting of cellulase, pectinase and neutral protease, adjust the pH to 3.5, extract at 35°C for 4 h, filter the filtrate, and concentrate the filtrate to obtain extract A;

[0062] (3) Grind Panax notoginseng into 80 mesh to obtain Panax notoginseng coarse powder, add 6 times the amount of water, adjust the pH value to 5.5 with HCl, heat to 100°C and extract for 1.5 hours; then adjust the pH value to 7 with NaOH, extract at 100°C for 1.5 hours, filter the filtrate, and concentrate the filtrate to obtain extract B;

[0063] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0064] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0065] The weight ratio of cellulase, pectinase and neutral protease is 2:1:0.3.

[0066] The mass fraction of the complex enzyme in water is 1%.

[0067] The auxiliary materials include one or more of fillers, disintegrants, stabilizers and lubricants.

[0068] The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of 0.3:0.9:0.1:1.

[0069] The ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.2:1.

[0070] The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:1.3:0.2.

[0071] The stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.3.

[0072] The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.2:1:1.4.

[0073] The preparation method of the modified starch is:

[0074] (1) Mixing starch and water in a mass ratio of 1:10 to obtain starch milk;

[0075] (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 15 minutes, heating to 45° C. and keeping the temperature for reaction for 12 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch;

[0076] (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 15 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch;

[0077] (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

[0078] The amount of sodium hydroxide added is 1% of the dry basis mass of starch.

[0079] The added amount of propylene oxide is 10% of the dry basis mass of starch.

[0080] The starch is corn starch. Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0081] The added amount of hexadecenylsuccinic anhydride is 12% of the dry basis mass of starch.

[0082] The lubricant is micro powder silica gel.

[0083] Comparative Example 1

[0084] The difference between this comparative example and Example 1 is that a composite enzyme consisting of ficin, bromelain and alkaline protease is added.

[0085] A method for preparing a compound danshen tablet comprises the following steps:

[0086] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0087] (2) crushing Danshen to 60 mesh, adding 12 times the amount of water, adding a complex enzyme consisting of ficin, bromelain and alkaline protease, adjusting the pH to 4, extracting at 42°C for 8 h, filtering the filtrate, and concentrating the filtrate to obtain extract A;

[0088] (3) Grind Panax notoginseng into 100 mesh to obtain Panax notoginseng coarse powder, add 10 times the amount of water, adjust the pH value to 6.5 with HCl, heat to 100°C and extract for 3 hours; then adjust the pH value to 9 with NaOH, extract at 100°C for 3 hours, filter the filtrate, and concentrate the filtrate to obtain extract B;

[0089] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0090] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0091] The weight ratio of ficin, bromelain and alkaline protease is 3:1:0.7.

[0092] The mass fraction of the complex enzyme in water is 3%.

[0093] The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of 0.5:1.3:0.5:1.

[0094] The ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.5:1.

[0095] The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:1.5:0.4.

[0096] The stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.5.

[0097] The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.5:1:1.7.

[0098] The preparation method of the modified starch is:

[0099] (1) Mixing starch and water in a mass ratio of 1:5 to obtain starch milk;

[0100] (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 25 minutes, heating to 55° C. and keeping the temperature for 16 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch;

[0101] (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 20 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch;

[0102] (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

[0103] The amount of sodium hydroxide added is 4% of the dry weight of starch.

[0104] The added amount of propylene oxide is 15% of the dry basis mass of starch.

[0105] The starch is corn starch. Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0106] The added amount of hexadecenylsuccinic anhydride is 17% of the dry basis weight of starch.

[0107] The lubricant is sodium stearyl fumarate.

[0108] Comparative Example 2

[0109] The difference between this comparative example and Example 1 is that the weight ratio of cellulase, pectinase and neutral protease is 1:1:1.

[0110] A method for preparing a compound danshen tablet comprises the following steps:

[0111] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0112] (2) crushing Danshen into 60 mesh, adding 12 times the amount of water, adding a complex enzyme consisting of cellulase, pectinase and neutral protease, adjusting the pH to 4, extracting at 42°C for 8 h, filtering the filtrate, and concentrating the filtrate to obtain extract A;

[0113] (3) Grind Panax notoginseng into 100 mesh to obtain Panax notoginseng coarse powder, add 10 times the amount of water, adjust the pH value to 6.5 with HCl, heat to 100°C and extract for 3 hours; then adjust the pH value to 9 with NaOH, extract at 100°C for 3 hours, filter the filtrate, and concentrate the filtrate to obtain extract B;

[0114] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0115] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0116] The weight ratio of cellulase, pectinase and neutral protease is 1:1:1.

[0117] The mass fraction of the complex enzyme in water is 3%.

[0118] The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of 0.5:1.3:0.5:1.

[0119] The ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.5:1.

[0120] The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:1.5:0.4.

[0121] The stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.5.

[0122] The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.5:1:1.7.

[0123] The preparation method of the modified starch is:

[0124] (1) Mixing starch and water in a mass ratio of 1:5 to obtain starch milk;

[0125] (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 25 minutes, heating to 55° C. and keeping the temperature for 16 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch;

[0126] (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 20 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch;

[0127] (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

[0128] The amount of sodium hydroxide added is 4% of the dry weight of starch.

[0129] The added amount of propylene oxide is 15% of the dry basis mass of starch.

[0130] The starch is corn starch. Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0131] The added amount of hexadecenylsuccinic anhydride is 17% of the dry basis weight of starch.

[0132] The lubricant is sodium stearyl fumarate.

[0133] Comparative Example 3

[0134] The difference between this comparative example and Example 1 is as follows: weigh the raw materials: 450g of Danshen, 141g of Panax notoginseng, and 8g of Borneol; for the above three ingredients, Danshen is heated and refluxed with ethanol for 1.5 hours, the extract is filtered, the filtrate is recovered with ethanol and concentrated to an appropriate amount for standby use; the medicinal residue is heated and refluxed with 50% ethanol for 1.5 hours, the extract is filtered, the filtrate is recovered with ethanol and concentrated to an appropriate amount for standby use; the medicinal residue is decocted with water for 2 hours, the decoction is filtered, and the filtrate is concentrated to an appropriate amount. Panax notoginseng is crushed into fine powder, made into granules with the above concentrate and auxiliary materials, and dried. Borneol is ground into fine powder, mixed with the above granules, pressed into tablets, and coated with a film to obtain compound Danshen tablets.

[0135] Comparative Example 4

[0136] The difference between this comparative example and Example 1 is that the disintegrants are low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 1:1:1.

[0137] A method for preparing a compound danshen tablet comprises the following steps:

[0138] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0139] (2) crushing Danshen into 60 mesh, adding 12 times the amount of water, adding a complex enzyme consisting of cellulase, pectinase and neutral protease, adjusting the pH to 4, extracting at 42°C for 8 h, filtering the filtrate, and concentrating the filtrate to obtain extract A;

[0140] (3) Grind Panax notoginseng into 100 mesh to obtain Panax notoginseng coarse powder, add 10 times the amount of water, adjust the pH value to 6.5 with HCl, heat to 100°C and extract for 3 hours; then adjust the pH value to 9 with NaOH, extract at 100°C for 3 hours, filter the filtrate, and concentrate the filtrate to obtain extract B;

[0141] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0142] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0143] The weight ratio of cellulase, pectinase and neutral protease is 3:1:0.7.

[0144] The mass fraction of the complex enzyme in water is 3%.

[0145] The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of 0.5:1.3:0.5:1.

[0146] The ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.5:1.

[0147] The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:1.5:0.4.

[0148] The stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.5.

[0149] The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 1:1:1.

[0150] The preparation method of the modified starch is:

[0151] (1) Mixing starch and water in a mass ratio of 1:5 to obtain starch milk;

[0152] (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 25 minutes, heating to 55° C. and keeping the temperature for 16 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch;

[0153] (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 20 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch;

[0154] (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

[0155] The amount of sodium hydroxide added is 4% of the dry weight of starch.

[0156] The added amount of propylene oxide is 15% of the dry basis mass of starch.

[0157] The starch is corn starch. Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.

[0158] The added amount of hexadecenylsuccinic anhydride is 17% of the dry basis weight of starch.

[0159] The lubricant is sodium stearyl fumarate.

[0160] Comparative Example 5

[0161] The difference between this comparative example and Example 1 is that the disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and starch in a mass ratio of 1:1:1.

[0162] A method for preparing a compound danshen tablet comprises the following steps:

[0163] (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol;

[0164] (2) crushing Danshen into 60 mesh, adding 12 times the amount of water, adding a complex enzyme consisting of cellulase, pectinase and neutral protease, adjusting the pH to 4, extracting at 42°C for 8 h, filtering the filtrate, and concentrating the filtrate to obtain extract A;

[0165] (3) Grind Panax notoginseng into 100 mesh to obtain Panax notoginseng coarse powder, add 10 times the amount of water, adjust the pH value to 6.5 with HCl, heat to 100°C and extract for 3 hours; then adjust the pH value to 9 with NaOH, extract at 100°C for 3 hours, filter the filtrate, and concentrate the filtrate to obtain extract B;

[0166] (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying;

[0167] (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

[0168] The weight ratio of cellulase, pectinase and neutral protease is 3:1:0.7.

[0169] The mass fraction of the complex enzyme in water is 3%.

[0170] The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of 0.5:1.3:0.5:1.

[0171] The ratio of the weight of the auxiliary material to the total weight of extract A and extract B is 1.5:1.

[0172] The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1:1.5:0.4.

[0173] The stabilizer is sodium carboxymethyl cellulose and α-cyclodextrin in a mass ratio of 1:1.5.

[0174] The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.5:1:1.7.

[0175] The lubricant is sodium stearyl fumarate.

[0176] Performance Testing

[0177] The content of the compound Danshen tablets prepared in Examples 1-2 and Comparative Examples 1-5 was determined. The results are shown in Table 1.

[0178] Table 1 Tanshinone II in Compound Danshen Tablets A , Danshensu, protocatechuic aldehyde content determination

[0179]

[0180] It can be seen from the above performance test results that Examples 1-2 have high contents of tanshinone ⅡA, tanshinone and protocatechuic aldehyde, while the comparative example does not adopt the necessary technical scheme, resulting in its corresponding performance test being significantly worse than that of the embodiment. The above experimental results further prove the importance of the technical scheme defined in the present invention for its technical effect.

[0181] High temperature conditions help accelerate the dissolution of the active ingredients and also help improve the extraction efficiency. At the same time, adding modified starch to the disintegrant of the present invention can reduce the time it takes for the Danshen tablets to completely disintegrate.

[0182] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a compound Danshen tablet, characterized in that: The following steps are involved: (1) Weigh the raw materials: 450 g of Salvia miltiorrhiza, 141 g of Panax notoginseng, and 8 g of Borneol; (2) Crush the salvia miltiorrhiza to 30-60 mesh, add 10-12 times the amount of water, add a complex enzyme consisting of cellulase, pectinase and neutral protease, adjust the pH to 3.5-4, extract at 35°C-42°C for 4-8 hours, filter to obtain a filtrate, and concentrate the filtrate to obtain extract A; (3) Grind Panax notoginseng into 80-100 mesh to obtain Panax notoginseng coarse powder, add 6-10 times amount of water, adjust the pH value to 5.5-6.5 with HCl, heat to 100°C and extract for 1.5h-3h; then adjust the pH value to 7-9 with NaOH, extract at 100°C for 1.5h-3h, filter to obtain the filtrate, and concentrate the filtrate to obtain extract B; (3) Mixing extract A and extract B with auxiliary materials, forming granules, and drying; (4) Grind the borneol into fine powder, mix it with the granules, press it into tablets, and coat it with a film to obtain compound danshen tablets.

2. The method for preparing the compound Danshen tablet according to claim 1, characterized in that: The weight ratio of cellulase, pectinase and neutral protease is (2-3):1:(0.3-0.7).

3. The method for preparing the compound Danshen tablet according to claim 1, characterized in that: The auxiliary materials include a filler, a disintegrant, a stabilizer and a lubricant in a weight ratio of (0.3-0.5):(0.9-1.3):(0.1-0.5):

1.

4. The method for preparing the compound Danshen tablet according to claim 3, characterized in that: The ratio of the weight of the auxiliary material to the total weight of the extract A and the extract B is 1.2-1.5:

1.

5. The method for preparing the compound Danshen tablet according to claim 3, characterized in that: The filler is microcrystalline cellulose, lactose and sucrose in a mass ratio of 1: (1.3-1.5): (0.2-0.4).

6. The method for preparing the compound Danshen tablet according to claim 3, characterized in that: The stabilizer is sodium carboxymethyl cellulose and alpha-cyclodextrin in a mass ratio of 1:1.3-1.

5.

7. The method for preparing the compound Danshen tablet according to claim 3, characterized in that: The disintegrant is low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and modified starch in a mass ratio of 0.2-0.5:1:1.4-1.

7.

8. The method for preparing the compound Danshen tablet according to claim 1, characterized in that: The preparation method of the modified starch is: (1) Mixing starch and water in a mass ratio of 1 to 2:10 to obtain starch milk; (2) adding sodium hydroxide and propylene oxide to the starch emulsion, sealing and standing for 15 to 25 minutes, heating to 45 to 55° C. and keeping the temperature for reaction for 12 to 16 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain hydroxypropyl starch; (3) adding hexadecenylsuccinic anhydride to hydroxypropyl starch, reacting for 15 to 20 hours, and neutralizing with a 20 wt % hydrochloric acid aqueous solution to a neutral pH to obtain esterified starch; (4) The esterified starch was washed twice with water and ethanol respectively, filtered, dried, crushed and passed through a 100-mesh sieve to obtain modified starch.

9. The method for preparing compound Danshen tablets according to claim 1, characterized in that: The lubricant is selected from one or more of sodium stearyl fumarate, micro powder silica gel, and magnesium stearate.

10. Compound Danshen tablets prepared by the preparation method according to any one of claims 1 to 9.

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