Betaine composition with antihypertensive effect and preparation method thereof

Abstract

The invention discloses a betaine composition with an antihypertensive effect and a preparation method thereof, and belongs to the technical field of pharmaceutical compositions.The preparation method comprises the steps of tablet core preparation, primary coating liquid preparation, secondary coating liquid preparation, primary coating and secondary coating; the step of preparing the primary coating liquid comprises the steps of preparing a filling agent and performing primary mixing; the step of preparing the secondary coating solution comprises the steps of preparing a supramolecular composition and performing secondary mixing; according to the prepared betaine composition, the problem that the blood pressure is too low after the prepared betaine composition is used can be avoided by controlling the release speed of the angiotensin converting enzyme inhibitor, and the prepared betaine composition is good in storage resistance, high in percent of pass and suitable for industrial production. And the content difference of the angiotensin converting enzyme inhibitor in the prepared betaine mixture is small.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical compositions, and in particular to a betaine composition having a blood pressure lowering effect and a preparation method thereof. Background Art

[0002] Betaine is an alkaloid with the appearance of white crystalline powder, odorless and sweet. Its chemical name is N,N,N-trimethylglycine. The chemical structure of betaine is similar to that of amino acids and it belongs to the quaternary ammonium base class. Betaine is widely found in animals, plants and microorganisms. The commonly used preparation methods of betaine are extraction from the roots, stems, leaves and fruits of natural plants and chemical synthesis using trimethylamine and chloroacetic acid as raw materials.

[0003] In mammals, betaine mainly plays the role of maintaining the osmotic balance inside and outside cells and providing methyl groups. Specifically, first, as a natural compound, betaine has a bipolar structure, is extremely soluble in water, and has a low degree of interaction with enzymes and metabolic processes in cells. Therefore, betaine not only plays an important role in protecting cells, proteins and enzymes, but also maintains cell function under various environmental pressures such as low water, high salt and extreme temperatures; second, in the methylation reaction in the body, betaine can promote the conversion of homocysteine ​​to methionine by providing methyl groups.

[0004] Betaine also has the following pharmacological effects in mammals: first, anti-fatty liver, specifically betaine can increase the phospholipid level in the blood and liver, thereby playing an anti-fatty liver role; second, anti-hypertensive, specifically betaine can dilate peripheral blood vessels and reduce peripheral vascular resistance, thereby playing a anti-hypertensive role; third, anti-tumor, specifically betaine can inhibit the mitosis of tumor cells in vitro, thereby playing an anti-tumor role.

[0005] Hypertension is a phenomenon in which the pressure value on the blood vessel wall caused by blood flow is continuously higher than normal. The causes of hypertension are mostly genetic factors and unhealthy lifestyles, such as high-salt diet, excessive drinking, long-term mental stress and lack of physical activity. Typical symptoms of hypertension include headache, fatigue or restlessness, arrhythmia, palpitations and tinnitus. For patients with hypertension, one of the commonly used treatments is drug therapy. The antihypertensive drugs used mainly include calcium antagonists, angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, diuretics and beta-blockers. Among them, the antihypertensive effect of angiotensin converting enzyme inhibitors is clear. By reducing the production of angiotensin II, it reduces peripheral vasoconstriction, dilates peripheral blood vessels, and reduces peripheral vascular resistance, which further plays a role in lowering blood pressure. Commonly used angiotensin converting enzyme inhibitors include enalapril, captopril, benazepril hydrochloride, etc., but angiotensin converting enzyme inhibitors have the problem of slow onset.

[0006] Clinical trials have shown that the betaine composition obtained by mixing betaine or its salt with an angiotensin converting enzyme inhibitor is used as a blood pressure lowering drug, wherein the betaine salt is betaine hydrochloride, betaine phosphate, or betaine citrate. The betaine or its salt in the betaine composition can reduce peripheral vascular resistance by dilating peripheral blood vessels, thereby increasing the speed of effect, further overcoming the problem of slow onset of effect when angiotensin converting enzyme inhibitor is used alone as a blood pressure lowering drug. However, further clinical trials have shown that when betaine or its salt is mixed with an angiotensin converting enzyme inhibitor and used, as the amount of angiotensin II generated decreases, it synergizes with the effect of betaine in dilating peripheral blood vessels, resulting in a blood pressure reduction peak, and further causing the problem of low blood pressure.

[0007] In view of the above problems, the most commonly used methods are: first, using betaine or its salt and angiotensin converting enzyme inhibitor separately, and controlling the amount of betaine or its salt used, but it is difficult to control the amount used; second, after the angiotensin converting enzyme inhibitor is sustained-released, it is mixed with betaine or its salt and then tableted to prepare a betaine mixture, thereby reducing the action rate of the angiotensin converting enzyme inhibitor. Commonly used sustained-release methods include coating method, microencapsulation method, and skeleton sustained-release method. However, when the sustained-release angiotensin converting enzyme inhibitor is mixed with betaine or its salt, there is a problem of uneven dispersion due to different particle sizes, resulting in a large difference in the content of angiotensin converting enzyme inhibitor between the prepared betaine mixtures. In addition, for the sustained-release angiotensin converting enzyme inhibitor prepared by the microencapsulation method, after mixing with betaine or its salt, betaine or its salt is adsorbed on the surface of the sustained-release angiotensin converting enzyme inhibitor. Due to the strong hygroscopicity of betaine or its salt, in the long term During storage, the coating film or microcapsule film of betaine or its salt will be destroyed, resulting in a decrease in the sustained-release effect. Therefore, the sustained-release angiotensin converting enzyme inhibitor prepared by the microencapsulation method has the problem of poor storage resistance. For the sustained-release angiotensin converting enzyme inhibitor prepared by the coating method, not only does it have the same problem as the sustained-release angiotensin converting enzyme inhibitor prepared by the microencapsulation method, but it will also cause the coating film to rupture during tableting, further affecting the sustained-release effect. For the sustained-release angiotensin converting enzyme inhibitor prepared by the skeleton sustained-release method, after mixing with betaine or its salt, betaine or its salt is adsorbed in the sustained-release skeleton of the sustained-release angiotensin converting enzyme inhibitor. Since betaine or its salt has strong hygroscopicity, it will destroy the sustained-release skeleton during long-term storage, affecting the sustained-release effect of the sustained-release skeleton, resulting in the problem of initial burst release of the prepared betaine mixture. Therefore, the sustained-release angiotensin converting enzyme inhibitor prepared by the skeleton sustained-release method also has the problem of poor storage resistance.

[0008] The inventors also tried to prepare a betaine mixture by coating the surface of a sustained-release angiotensin-converting enzyme inhibitor with a coating solution containing betaine or its salt to form a primary coating film, and then using a hydrophobic coating material to perform a secondary coating to form a secondary coating film. Although the storage stability of the prepared betaine mixture can be improved, there is a lack of hydrogen bonding between the primary coating film and the secondary coating film, and the bonding force is poor, resulting in the problem of powdering and roughness on the surface of the prepared betaine mixture, and the qualified rate is low. Summary of the invention

[0009] In view of the deficiencies in the prior art, the present invention provides a betaine composition with a blood pressure lowering effect and a preparation method thereof. The prepared betaine composition can avoid the problem of low blood pressure after use of the prepared betaine composition by controlling the release rate of angiotensin converting enzyme inhibitors. The prepared betaine mixture has good storage stability and a high pass rate, and the content difference of angiotensin converting enzyme inhibitors between the prepared betaine mixtures is small.

[0010] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows: A method for preparing a betaine composition having a blood pressure lowering effect, comprising: preparing a tablet core, preparing a primary coating solution, preparing a secondary coating solution, primary coating, and secondary coating; The tablet core is prepared by grinding angiotensin converting enzyme inhibitor, microcrystalline cellulose, hydroxypropyl methylcellulose mixture, cross-linked polyvinylpyrrolidone and magnesium stearate respectively, and passing through a 100-mesh sieve to obtain the ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ground magnesium stearate; the ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ultrapure water are mixed, and then passed through a 24-mesh sieve to prepare wet granules, which are dried at 50-60° C. for 55-60 min, passed through a 24-mesh sieve to obtain whole granules, and then mixed with the ground magnesium stearate, and then tableted to obtain the tablet core; In the prepared tablet core, the angiotensin converting enzyme inhibitor is one of enalapril, captopril, and benazepril hydrochloride; The hydroxypropyl methylcellulose composition is a mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M, wherein the mass ratio of the mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M is 1:1-1.2; The mass ratio of the crushed angiotensin converting enzyme inhibitor, crushed microcrystalline cellulose, crushed hydroxypropyl methylcellulose mixture, crushed cross-linked polyvinylpyrrolidone, ultrapure water, and crushed magnesium stearate is 40-45:100-110:45-55:3-4:50-60:24-27; The pressure during tableting is 30-35N; The method of preparing a coating solution comprises: preparing a filler and mixing it once; The filler is prepared by mixing hydroxypropyl-β-cyclodextrin and the first portion of ultrapure water, stirring the mixture, controlling the stirring temperature to 25-40° C. and the stirring speed to 100-300 rpm, stirring for 20-30 min, keeping the temperature and stirring speed unchanged, adding micropowder silica gel, stirring for 2-3 h, centrifuging, controlling the speed of centrifugation to 2500-3000 rpm, centrifuging for 10-15 min, mixing the precipitate with the second portion of ultrapure water, stirring the mixture, controlling the stirring temperature to 25-40° C. and the stirring speed to 100-300 rpm, stirring for 5-10 min, heating to 85-95° C., keeping the stirring speed unchanged, stirring and reflux, adding citric acid aqueous solution, stirring and refluxing for 3.5-4 h, centrifuging, controlling the speed of centrifugation to 2500-3000 rpm, centrifuging for 10-15 min, washing the precipitate 4-6 times with ultrapure water, and then drying at 110-130° C. to obtain the filler; In the preparation of the filler, the dosage ratio of hydroxypropyl-β-cyclodextrin, the first portion of ultrapure water, micropowder silica gel, the second portion of ultrapure water, and citric acid aqueous solution is 50-60 g: 1000-1100 mL: 100-110 g: 1000-1100 mL: 550-650 mL; The particle size of the micropowder silica gel is 5 μm; The mass concentration of the citric acid aqueous solution is 20%; The primary mixing comprises mixing the filler and ultrapure water and stirring the mixture. The temperature during stirring is controlled to be 30-50° C. and the stirring speed is controlled to be 100-300 rpm. After stirring for 20-30 minutes, the temperature and the stirring speed are kept unchanged, betaine or its salt is added, and the mixture is stirred for 2-2.5 hours. The temperature and the stirring speed are kept unchanged, and hydroxypropyl methylcellulose is added, and the mixture is stirred for 1-1.5 hours to obtain a primary coating solution. In the primary mixing, the usage ratio of filler, ultrapure water, betaine or its salt, and hydroxypropyl methylcellulose is 120-130 g: 1000-1100 mL: 45-50 g: 50-55 g; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The betaine or its salt is one of betaine, betaine hydrochloride, betaine phosphate and betaine citrate; The method for preparing the secondary coating solution comprises: preparing a supramolecular composition and performing secondary mixing; The method for preparing the supramolecular composition comprises mixing β-cyclodextrin and ultrapure water and stirring the mixture, controlling the stirring temperature to be 25-40° C. and the stirring speed to be 100-300 rpm, stirring for 20-30 minutes, adding an aqueous solution of betaine or its salt, stirring for 20-30 minutes, spray drying, controlling the air inlet temperature to be 130-150° C. and the air outlet temperature to be 70-80° C. during spray drying, and obtaining the supramolecular composition; In the preparation of the supramolecular composition, the dosage ratio of β-cyclodextrin, ultrapure water, and an aqueous solution of betaine or its salt is 9-9.2 g: 500-550 mL: 140-160 mL; The mass concentration of the aqueous solution of betaine or its salt is 20%; The betaine or its salt in the aqueous solution of betaine or its salt is one of betaine, betaine hydrochloride, betaine phosphate and betaine citrate; The secondary mixing comprises mixing ethyl cellulose, hydroxypropyl methyl cellulose, triethyl citrate, micropowder silica gel, supramolecular composition and ethanol solution and stirring the mixture. The stirring temperature is controlled to be 30-50° C. and the stirring speed is controlled to be 100-300 rpm. After stirring for 50-60 minutes, a secondary coating solution is obtained. In the secondary mixing, the dosage ratio of ethyl cellulose, hydroxypropyl methyl cellulose, triethyl citrate, micropowder silica gel, supramolecular composition and ethanol solution is 40-43 g: 10-12 g: 10-12 g: 1.8-2 g: 7-8 g: 950-1000 mL; The ethyl cellulose is ethyl cellulose N10; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The volume concentration of the ethanol solution is 85%; The primary coating comprises placing the tablet core in a fluidized bed coating machine for heat preservation, keeping the temperature constant, and performing a primary coating using a primary coating liquid to obtain a primary coating layer; In the primary coating, the temperature during the heat preservation is 50-55°C, and the heat preservation time is 9-10 minutes; The primary coating weight gain is 5-5.3%; The secondary coating comprises placing the primary coating material into a fluidized bed coating machine for heat preservation, maintaining the temperature constant, and performing secondary coating with the secondary coating liquid to obtain a betaine composition having a blood pressure lowering effect; In the secondary coating, the temperature during the heat preservation is 50-55°C, and the heat preservation time is 9-10min; The secondary coating weight gain is 2.8-3%; A betaine composition with blood pressure lowering effect prepared by the above-mentioned preparation method.

[0011] Compared with the prior art, the present invention has the following beneficial effects: (1) The method for preparing the betaine composition with antihypertensive effect of the present invention comprises the following steps: coating a core tablet containing an angiotensin converting enzyme inhibitor with a primary coating solution containing betaine or its salt and a secondary coating solution in sequence, wherein the primary coating solution contains a filler. When preparing the filler, firstly, hydroxypropyl-β-cyclodextrin is adsorbed on the surface of the micro-powder silica gel using micro-powder silica gel, thereby adsorbing a layer of hydroxypropyl-β-cyclodextrin on the surface of the micro-powder silica gel, and then mixing the filler with a citric acid aqueous solution, wherein the citric acid cross-links with the hydroxypropyl-β-cyclodextrin on the surface, thereby coating the surface of the micro-powder silica gel with a layer of a cross-linked product of hydroxypropyl-β-cyclodextrin and citric acid, and obtaining the filler. After the filler is mixed with betaine or its salt, betaine or its salt is adsorbed on the surface of the cross-linked product of hydroxypropyl-β-cyclodextrin and citric acid. On the one hand, the cross-linked product of hydroxypropyl-β-cyclodextrin and citric acid can improve the dispersibility of micro-powder silica gel; on the other hand, the cross-linked product of hydroxypropyl-β-cyclodextrin and citric acid can fix and protect betaine or its salt through interaction with betaine or its salt, thereby reducing the hygroscopicity of betaine or its salt; on the third hand, the cross-linked product of hydroxypropyl-β-cyclodextrin and citric acid can be adsorbed on the surface of the intestine, and has a sustained-release effect on betaine or its salt; on the fourth hand, the cross-linked product of hydroxypropyl-β-cyclodextrin and citric acid can improve the dispersibility of micro-powder silica gel; on the other ... The cross-linked product contains a large number of ester groups and hydroxyl groups, which can improve the interaction with the ethyl cellulose in the secondary coating solution and improve the qualified rate of the prepared betaine composition; the secondary coating solution contains a supramolecular composition, which is a composition of β-cyclodextrin and betaine or its salt, and the hydroxyl groups on the outer layer of β-cyclodextrin interact with the nitrogen atoms in betaine or its salt, thereby reducing the hygroscopicity of the hydrophilic groups in β-cyclodextrin and betaine or its salt; the secondary coating solution also contains ethyl cellulose, which is insoluble in water, thereby further improving the storage resistance of the prepared betaine composition; after using the betaine composition prepared by the present invention, firstly the outermost The coating layer of the first layer is broken, and the supramolecular composition is dissolved. The β-cyclodextrin in the supramolecular composition can promote the absorption of betaine or its salt. Then the coating layer of the second outer layer is broken, and the betaine or its salt is evenly released, thereby avoiding the problem of low blood pressure caused by too fast release. Finally, the angiotensin converting enzyme inhibitor in the tablet core is evenly released, thereby reducing the generation of angiotensin II. After the release of betaine or its salt is completed, it can still continue to play a certain role in reducing peripheral vasoconstriction and dilating peripheral blood vessels, thereby controlling the release rate of the angiotensin converting enzyme inhibitor and avoiding the problem of low blood pressure after the prepared betaine composition is used. (2) The method for preparing the betaine composition with antihypertensive effect of the present invention can avoid the problem of hypotension after use of the prepared betaine composition by controlling the release rate of the angiotensin converting enzyme inhibitor. The dissolution of the betaine composition with antihypertensive effect prepared by the present invention is tested according to the second method paddle method in the second step of the dissolution determination method of the 2010 edition of the Chinese Pharmacopoeia, with distilled water as the dissolution medium, the temperature being controlled at 37°C, the rotation speed being 50 rpm, and the dissolution rate being 2.5 hours. The dissolution rate of angiotensin converting enzyme inhibitors was 10.10-10.51% at 4 h, 20.58-21.22% at 4 h, 48.22-49.10% at 8 h, 68.76-69.83% at 12 h, and 98.01-99.13% at 24 h. (3) The preparation method of the betaine composition with antihypertensive effect of the present invention, the prepared betaine mixture has good storage stability, and the betaine composition with antihypertensive effect prepared by the present invention is placed in an environment with a temperature of 25°C and a relative humidity of 92.5% for 7 days, and the weight gain rate is 0.085-0.092%; (4) The method for preparing the betaine composition with blood pressure lowering effect of the present invention has a high qualified rate of the prepared betaine mixture, which can reach 98.9-99.4%; (5) The method for preparing the betaine composition with antihypertensive effect of the present invention has a small difference in the content of angiotensin converting enzyme inhibitor between the prepared betaine mixtures. 20 tablets are randomly selected from the betaine composition with antihypertensive effect prepared by the present invention, and the content of angiotensin converting enzyme inhibitor therein is tested, and the largest content of angiotensin converting enzyme inhibitor is used as the dividend and the smallest content of angiotensin converting enzyme inhibitor is used as the divisor, and the division result obtained is 1.016-1.025. DETAILED DESCRIPTION

[0012] In order to have a clearer understanding of the technical features, purposes and effects of the present invention, the specific implementation methods of the present invention are now described.

[0013] Example 1 A method for preparing a betaine composition having a blood pressure lowering effect, specifically comprising: 1. Preparing tablet cores: grinding angiotensin converting enzyme inhibitor, microcrystalline cellulose, hydroxypropyl methylcellulose mixture, cross-linked polyvinylpyrrolidone and magnesium stearate respectively, passing through a 100-mesh sieve to obtain a ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ground magnesium stearate; mixing the ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ultrapure water, passing through a 24-mesh sieve to prepare wet granules, drying at 50° C. for 55 min, passing through a 24-mesh sieve to obtain whole granules, and then mixing with the ground magnesium stearate, and tableting, controlling the pressure during tableting to be 30 N to obtain tablet cores; The angiotensin converting enzyme inhibitor is enalapril; The hydroxypropyl methylcellulose composition is a mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M, wherein the mass ratio of the mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M is 1:1; The mass ratio of the crushed angiotensin converting enzyme inhibitor, crushed microcrystalline cellulose, crushed hydroxypropyl methylcellulose mixture, crushed cross-linked polyvinylpyrrolidone, ultrapure water, and crushed magnesium stearate is 40:100:45:3:50:24; 2. Prepare the primary coating solution: (1) Preparation of filler: 50 g of hydroxypropyl-β-cyclodextrin and 1000 mL of ultrapure water were mixed and stirred, and the stirring temperature was controlled at 25°C and the stirring speed was 100 rpm. After stirring for 20 min, the temperature and stirring speed were kept constant, 100 g of micro-powdered silica gel was added, and the mixture was stirred for 2 h. The mixture was centrifuged and the speed was controlled at 2500 rpm for 10 min. The precipitate was mixed with 1000 mL of ultrapure water and stirred, and the stirring temperature was controlled at 25°C and the stirring speed was 100 rpm for 5 min. The mixture was heated to 85°C and the stirring speed was kept constant. The mixture was stirred and refluxed. 550 mL of citric acid aqueous solution was added, and the mixture was stirred and refluxed for 3.5 h. The mixture was centrifuged and the speed was controlled at 2500 rpm for 10 min. The precipitate was washed with ultrapure water for 4 times, with 700 mL of ultrapure water used for each wash, and then dried at 110°C to obtain a filler; The particle size of the micropowder silica gel is 5 μm; The mass concentration of the citric acid aqueous solution is 20%; (2) Primary mixing: 120 g of filler and 1000 mL of ultrapure water were mixed and stirred. The temperature during stirring was controlled at 30°C and the stirring speed was controlled at 100 rpm. After stirring for 20 min, 45 g of betaine was added while maintaining the temperature and stirring speed unchanged. The mixture was stirred for 2 h. The temperature and stirring speed were continued to be maintained unchanged. 50 g of hydroxypropyl methylcellulose was added and stirred for 1 h to obtain a primary coating solution. The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; 3. Preparation of secondary coating solution: (1) Preparation of supramolecular composition: 9 g of β-cyclodextrin and 500 mL of ultrapure water were mixed and stirred, and the temperature during stirring was controlled to be 25° C. and the stirring speed was controlled to be 100 rpm. After stirring for 20 min, the temperature and stirring speed were kept constant, 140 mL of betaine aqueous solution was added, and the mixture was stirred for 20 min. The mixture was spray-dried, and the air inlet temperature during spray drying was controlled to be 130° C. and the air outlet temperature was controlled to be 70° C., to obtain a supramolecular composition; The mass concentration of the aqueous solution of betaine is 20%; (2) Secondary mixing: 40 g of ethyl cellulose, 10 g of hydroxypropyl methyl cellulose, 10 g of triethyl citrate, 1.8 g of micropowder silica gel, 7 g of supramolecular composition, and 950 mL of ethanol solution were mixed and stirred at a temperature of 30° C. and a stirring speed of 100 rpm. After stirring for 50 min, a secondary coating solution was obtained; The ethyl cellulose is ethyl cellulose N10; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The volume concentration of the ethanol solution is 85%; 4. Primary coating: put the tablet core into a fluidized bed coater for heat preservation, control the temperature during heat preservation to 50°C, keep warm for 9 minutes, keep the temperature constant, use the primary coating liquid for a single coating, control the coating weight gain to 5%, and obtain a primary coating layer; 5. Secondary coating: Place the primary coating material into a fluidized bed coating machine for heat preservation, control the temperature during heat preservation to 50°C, keep the temperature for 9 minutes, keep the temperature constant, use the secondary coating liquid for secondary coating, control the coating weight gain to 2.8%, and obtain a betaine composition with antihypertensive effect.

[0014] This embodiment also provides a betaine composition having a blood pressure lowering effect prepared by the aforementioned preparation method.

[0015] Example 2 A method for preparing a betaine composition having a blood pressure lowering effect, specifically comprising: 1. Preparing tablet cores: grinding angiotensin converting enzyme inhibitor, microcrystalline cellulose, hydroxypropyl methylcellulose mixture, cross-linked polyvinylpyrrolidone and magnesium stearate respectively, passing through a 100-mesh sieve to obtain a ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ground magnesium stearate; mixing the ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ultrapure water, passing through a 24-mesh sieve to prepare wet granules, drying at 55° C. for 57 min, passing through a 24-mesh sieve to obtain whole granules, and then mixing with the ground magnesium stearate, and tableting, controlling the tableting pressure to be 32 N to obtain tablet cores; The angiotensin converting enzyme inhibitor is captopril; The hydroxypropyl methylcellulose composition is a mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M, wherein the mass ratio of the mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M is 1:1.1; The mass ratio of the crushed angiotensin converting enzyme inhibitor, crushed microcrystalline cellulose, crushed hydroxypropyl methylcellulose mixture, crushed cross-linked polyvinylpyrrolidone, ultrapure water, and crushed magnesium stearate is 42:103:48:3.2:53:25; 2. Prepare the primary coating solution: (1) Preparation of filler: 52 g of hydroxypropyl-β-cyclodextrin and 1020 mL of ultrapure water were mixed and stirred, and the stirring temperature was controlled at 28°C and the stirring speed was 200 rpm. After stirring for 22 min, the temperature and stirring speed were kept constant. 102 g of micro-powdered silica gel was added, and the mixture was stirred for 2.5 h. The mixture was centrifuged and the speed was controlled at 2600 rpm for 11 min. The precipitate was mixed with 1040 mL of ultrapure water and stirred, and the stirring temperature was controlled at 30°C and the stirring speed was 150 rpm for 8 min. The mixture was heated to 90°C and the stirring speed was kept constant. The mixture was stirred and refluxed. 580 mL of citric acid aqueous solution was added, and the mixture was stirred and refluxed for 3.5 h. The mixture was centrifuged and the speed was controlled at 2700 rpm for 11 min. The precipitate was washed 5 times with ultrapure water, using 750 mL of ultrapure water for each wash, and then dried at 120°C to obtain a filler. The particle size of the micropowder silica gel is 5 μm; The mass concentration of the citric acid aqueous solution is 20%; (2) Primary mixing: 122 g of filler and 1030 mL of ultrapure water were mixed and stirred. The temperature during stirring was controlled at 35°C and the stirring speed was controlled at 150 rpm. After stirring for 23 min, 46 g of betaine hydrochloride was added while maintaining the temperature and stirring speed unchanged. The mixture was stirred for 2 h. The temperature and stirring speed were continued to be maintained unchanged. 52 g of hydroxypropyl methylcellulose was added and stirred for 1 h to obtain a primary coating solution. The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; 3. Preparation of secondary coating solution: (1) Preparation of supramolecular composition: 9.1 g of β-cyclodextrin and 510 mL of ultrapure water were mixed and stirred, and the temperature during stirring was controlled to be 30° C. and the stirring speed was controlled to be 100 rpm. After stirring for 23 min, the temperature and stirring speed were kept constant, 145 mL of an aqueous solution of betaine hydrochloride was added, and the mixture was stirred for 23 min. The mixture was spray-dried, and the air inlet temperature during spray drying was controlled to be 135° C. and the air outlet temperature was controlled to be 72° C., thereby obtaining a supramolecular composition; The mass concentration of the aqueous solution of betaine hydrochloride is 20%; (2) Secondary mixing: 41 g of ethyl cellulose, 10.5 g of hydroxypropyl methyl cellulose, 10.5 g of triethyl citrate, 1.8 g of micropowder silica gel, 7.2 g of supramolecular composition, and 960 mL of ethanol solution were mixed and stirred. The stirring temperature was controlled to be 35° C. and the stirring speed was controlled to be 150 rpm. After stirring for 52 min, a secondary coating solution was obtained. The ethyl cellulose is ethyl cellulose N10; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The volume concentration of the ethanol solution is 85%; 4. Primary coating: put the tablet core into a fluidized bed coater for heat preservation, control the temperature during heat preservation to 52°C, keep warm for 9.5 minutes, keep the temperature constant, use the primary coating liquid for a single coating, control the coating weight gain to 5.1%, and obtain a primary coating layer; 5. Secondary coating: Place the primary coating material into a fluidized bed coating machine for heat preservation, control the temperature during heat preservation to 52°C, keep the temperature for 9 minutes, keep the temperature constant, use the secondary coating liquid for secondary coating, control the coating weight gain to 2.8%, and obtain a betaine composition with antihypertensive effect.

[0016] This embodiment also provides a betaine composition having a blood pressure lowering effect prepared by the aforementioned preparation method.

[0017] Example 3 A method for preparing a betaine composition having a blood pressure lowering effect, specifically comprising: 1. Preparing tablet cores: grinding angiotensin converting enzyme inhibitor, microcrystalline cellulose, hydroxypropyl methylcellulose mixture, cross-linked polyvinylpyrrolidone and magnesium stearate respectively, passing through a 100-mesh sieve to obtain a ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ground magnesium stearate; mixing the ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ultrapure water, passing through a 24-mesh sieve to prepare wet granules, drying at 60° C. for 58 min, passing through a 24-mesh sieve to obtain whole granules, and then mixing with the ground magnesium stearate, and tableting, controlling the tableting pressure to be 34 N to obtain tablet cores; The angiotensin converting enzyme inhibitor is benazepril hydrochloride; The hydroxypropyl methylcellulose composition is a mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M, wherein the mass ratio of the mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M is 1:1.1; The mass ratio of the crushed angiotensin converting enzyme inhibitor, crushed microcrystalline cellulose, crushed hydroxypropyl methylcellulose mixture, crushed cross-linked polyvinylpyrrolidone, ultrapure water, and crushed magnesium stearate is 44:108:52:3.8:57:26; 2. Prepare the primary coating solution: (1) Preparation of filler: 60 g of hydroxypropyl-β-cyclodextrin and 1050 mL of ultrapure water were mixed and stirred, and the temperature during stirring was controlled at 35°C and the stirring speed was 250 rpm. After stirring for 28 min, the temperature and stirring speed were kept constant, 107 g of micro-powdered silica gel was added, and the mixture was stirred for 2.5 h. The mixture was centrifuged and the speed during centrifugation was controlled at 3000 rpm. The mixture was centrifuged for 14 min. The precipitate was mixed with 1080 mL of ultrapure water and stirred, and the temperature during stirring was controlled at 35°C and the stirring speed was 250 rpm. The mixture was stirred for 8 min. The mixture was heated to 95°C and the stirring speed was kept constant. The mixture was stirred and refluxed. 620 mL of citric acid aqueous solution was added, and the mixture was stirred and refluxed for 4 h. The mixture was centrifuged and the speed during centrifugation was controlled at 3000 rpm. The mixture was centrifuged for 14 min. The precipitate was washed 5 times with ultrapure water, using 850 mL of ultrapure water for each wash, and then dried at 125°C to obtain a filler; The particle size of the micropowder silica gel is 5 μm; The mass concentration of the citric acid aqueous solution is 20%; (2) Primary mixing: 128 g of filler and 1070 mL of ultrapure water were mixed and stirred. The temperature during stirring was controlled to be 45°C and the stirring speed was controlled to be 250 rpm. After stirring for 27 min, the temperature and stirring speed were kept constant, 48 g of betaine phosphate was added, and the mixture was stirred for 2.5 h. The temperature and stirring speed were kept constant, and 54 g of hydroxypropyl methylcellulose was added and the mixture was stirred for 1.5 h to obtain a primary coating solution. The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; 3. Preparation of secondary coating solution: (1) Preparing a supramolecular composition: 9.1 g of β-cyclodextrin and 540 mL of ultrapure water were mixed and stirred, and the temperature during stirring was controlled to be 35° C. and the stirring speed was controlled to be 250 rpm. After stirring for 28 minutes, the temperature and stirring speed were kept constant, 155 mL of an aqueous solution of betaine phosphate was added, and the mixture was stirred for 28 minutes. The mixture was spray-dried, and the inlet air temperature during spray drying was controlled to be 145° C. and the outlet air temperature was controlled to be 78° C., thereby obtaining a supramolecular composition; The mass concentration of the aqueous solution of betaine phosphate is 20%; (2) Secondary mixing: 42 g of ethyl cellulose, 11.5 g of hydroxypropyl methyl cellulose, 11.7 g of triethyl citrate, 2 g of micropowder silica gel, 7.7 g of supramolecular composition, and 980 mL of ethanol solution were mixed and stirred. The stirring temperature was controlled to be 45° C. and the stirring speed was controlled to be 250 rpm. After stirring for 57 min, a secondary coating solution was obtained. The ethyl cellulose is ethyl cellulose N10; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The volume concentration of the ethanol solution is 85%; 4. Primary coating: put the tablet core into a fluidized bed coater for heat preservation, control the temperature during heat preservation to 54°C, keep the temperature for 10 minutes, keep the temperature constant, use the primary coating liquid for a single coating, control the coating weight gain to 5.2%, and obtain a primary coating layer; 5. Secondary coating: Place the primary coating material into a fluidized bed coating machine for heat preservation, control the temperature during heat preservation to 54°C, keep it warm for 10 minutes, keep the temperature constant, use the secondary coating liquid for secondary coating, control the coating weight gain to 2.9%, and obtain a betaine composition with antihypertensive effect.

[0018] This embodiment also provides a betaine composition having a blood pressure lowering effect prepared by the aforementioned preparation method.

[0019] Example 4 A method for preparing a betaine composition having a blood pressure lowering effect, specifically comprising: 1. Preparing tablet cores: grinding angiotensin converting enzyme inhibitor, microcrystalline cellulose, hydroxypropyl methylcellulose mixture, cross-linked polyvinylpyrrolidone and magnesium stearate respectively, passing through a 100-mesh sieve to obtain a ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ground magnesium stearate; mixing the ground angiotensin converting enzyme inhibitor, ground microcrystalline cellulose, ground hydroxypropyl methylcellulose mixture, ground cross-linked polyvinylpyrrolidone and ultrapure water, passing through a 24-mesh sieve to prepare wet granules, drying at 60° C. for 60 min, passing through a 24-mesh sieve to obtain whole granules, and then mixing with the ground magnesium stearate, and tableting, controlling the tableting pressure to be 35 N to obtain tablet cores; The angiotensin converting enzyme inhibitor is enalapril; The hydroxypropyl methylcellulose composition is a mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M, wherein the mass ratio of the mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M is 1:1.2; The mass ratio of the crushed angiotensin converting enzyme inhibitor, crushed microcrystalline cellulose, crushed hydroxypropyl methylcellulose mixture, crushed cross-linked polyvinylpyrrolidone, ultrapure water, and crushed magnesium stearate is 45:110:55:4:60:27; 2. Prepare the primary coating solution: (1) Preparation of filler: 60 g of hydroxypropyl-β-cyclodextrin and 1100 mL of ultrapure water were mixed and stirred, and the stirring temperature was controlled at 40°C and the stirring speed was 300 rpm. After stirring for 30 min, the temperature and stirring speed were kept constant, 110 g of micro-powdered silica gel was added, and the mixture was stirred for 3 h. The mixture was centrifuged and the speed was controlled at 3000 rpm for 15 min. The precipitate was mixed with 1100 mL of ultrapure water and stirred, and the stirring temperature was controlled at 40°C and the stirring speed was 300 rpm for 10 min. The mixture was heated to 95°C and the stirring speed was kept constant. The mixture was stirred and refluxed. 650 mL of citric acid aqueous solution was added, and the mixture was stirred and refluxed for 4 h. The mixture was centrifuged and the speed was controlled at 3000 rpm for 15 min. The precipitate was washed 6 times with ultrapure water, with 900 mL of ultrapure water used for each wash, and then dried at 130°C to obtain a filler; The particle size of the micropowder silica gel is 5 μm; The mass concentration of the citric acid aqueous solution is 20%; (2) Primary mixing: 130 g of filler and 1100 mL of ultrapure water were mixed and stirred. The temperature during stirring was controlled at 50°C and the stirring speed was controlled at 300 rpm. After stirring for 30 min, the temperature and stirring speed were kept constant, 50 g of betaine citrate was added, and the mixture was stirred for 2.5 h. The temperature and stirring speed were kept constant, and 55 g of hydroxypropyl methylcellulose was added and stirred for 1.5 h to obtain a primary coating solution. The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; 3. Preparation of secondary coating solution: (1) Preparing a supramolecular composition: 9.2 g of β-cyclodextrin and 550 mL of ultrapure water were mixed and stirred, and the stirring temperature was controlled to be 40° C. and the stirring speed was controlled to be 300 rpm. After stirring for 30 min, the temperature and stirring speed were kept constant, 160 mL of an aqueous solution of betaine citrate was added, and the mixture was stirred for 30 min. The mixture was spray-dried, and the inlet air temperature during the spray drying was controlled to be 150° C. and the outlet air temperature was controlled to be 80° C., thereby obtaining a supramolecular composition; The mass concentration of the aqueous solution of betaine citrate is 20%; (2) Secondary mixing: 43 g of ethyl cellulose, 12 g of hydroxypropyl methyl cellulose, 12 g of triethyl citrate, 2 g of micropowder silica gel, 8 g of supramolecular composition, and 1000 mL of ethanol solution were mixed and stirred at a temperature of 50° C. and a stirring speed of 300 rpm. After stirring for 60 min, a secondary coating solution was obtained. The ethyl cellulose is ethyl cellulose N10; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The volume concentration of the ethanol solution is 85%; 4. Primary coating: put the tablet core into a fluidized bed coater for heat preservation, control the temperature during heat preservation to 55°C, keep the temperature for 10 minutes, keep the temperature constant, use the primary coating liquid for a single coating, control the coating weight gain to 5.3%, and obtain a primary coating layer; 5. Secondary coating: Place the primary coating liquid in a fluidized bed coating machine for heat preservation, control the temperature during heat preservation to 55°C, keep the temperature for 10 minutes, keep the temperature constant, use the secondary coating liquid for secondary coating, control the coating weight gain to 3%, and obtain a betaine composition with antihypertensive effect.

[0020] This embodiment also provides a betaine composition having a blood pressure lowering effect prepared by the aforementioned preparation method.

[0021] Comparative Example 1 This comparative example provides a method for preparing a betaine composition having a blood pressure lowering effect. The preparation method is adjusted based on the preparation method of Example 1. The specific adjustments are as follows: In the step (2) of preparing the primary coating solution, the step (1) of preparing the filler is omitted, and in the step (2) of secondary mixing, micro powder silica gel with a particle size of 5 μm is used as a filler.

[0022] This comparative example also provides a betaine composition having a blood pressure lowering effect prepared by the aforementioned preparation method.

[0023] Comparative Example 2 This comparative example provides a method for preparing a betaine composition having a blood pressure lowering effect. The preparation method is adjusted based on the preparation method of Example 1. The specific adjustments are as follows: In the step (3) of preparing the secondary coating solution, the step (1) of preparing the supramolecular composition was omitted, and in the step (2) of the secondary mixing step, 5.3 g of betaine was used instead of 7 g of the supramolecular composition.

[0024] This comparative example also provides a betaine composition having a blood pressure lowering effect prepared by the aforementioned preparation method.

[0025] Test Example 1 The release rates of the angiotensin converting enzyme inhibitor in the betaine compositions with blood pressure lowering effects prepared in Examples 1-4 and Comparative Examples 1-2 were tested respectively, and the testing methods and test results are as follows: According to the second paddle method in the second step of the dissolution determination method of the 2010 edition of the Chinese Pharmacopoeia, distilled water was used as the dissolution medium, the temperature was controlled at 37°C, the rotation speed was 50 rpm, and the dissolution of the angiotensin converting enzyme inhibitor in the betaine composition with hypotensive effect of Example 1-4 and Comparative Example 1-2 was tested at 2h, 4h, 8h, 12h, and 24h. The test results are as follows:

[0026] It can be seen from the results of this test example that the sustained-release effect of the betaine composition with antihypertensive effect prepared in Example 1 is better than that of the betaine composition with antihypertensive effect prepared in Comparative Examples 1-2.

[0027] Test Example 2 According to the preparation method of the betaine composition with blood pressure lowering effect of Examples 1-4 and Comparative Examples 1-2, 1000 capsules were prepared, and the qualified rates were counted respectively. The statistical results are as follows:

[0028] Then, 20 pills were randomly selected and the angiotensin converting enzyme inhibitor content therein was tested. The largest angiotensin converting enzyme inhibitor content was used as the dividend, and the smallest angiotensin converting enzyme inhibitor content was used as the divisor to obtain the division results. The statistical results are as follows:

[0029] It can be seen from the results of this test example that the qualified rate of the betaine composition with antihypertensive effect prepared in Example 1 is better than that of the betaine composition with antihypertensive effect prepared in Comparative Examples 1-2, and compared with the betaine composition with antihypertensive effect prepared in Comparative Examples 1-2, the difference in the content of angiotensin-converting enzyme inhibitor between the betaine mixtures prepared in Example 1 is small.

[0030] Test Example 3 The betaine compositions with blood pressure lowering effect prepared in Examples 1-4 and Comparative Examples 1-2 were respectively placed in an environment with a temperature of 25° C. and a relative humidity of 92.5% for 7 days, and then the weight gain rates were respectively counted. The statistical results are as follows:

[0031] It can be seen from the results of this test example that the storage stability of the betaine composition with a blood pressure lowering effect prepared in Example 1 is better than that of the betaine composition with a blood pressure lowering effect prepared in Comparative Examples 1-2.

[0032] Unless otherwise specified, all percentages used in the present invention are by mass.

[0033] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a betaine composition having a blood pressure lowering effect, characterized in that: include: Prepare tablet cores, prepare primary coating solution, prepare secondary coating solution, perform primary coating, and perform secondary coating; The method of preparing a coating solution comprises: preparing a filler and mixing it once; The filler is prepared by mixing hydroxypropyl-β-cyclodextrin and the first portion of ultrapure water and stirring, controlling the stirring temperature to 25-40° C., stirring, adding micropowdered silica gel, stirring, centrifuging, mixing the precipitate with the second portion of ultrapure water and stirring, controlling the stirring temperature to 25-40° C., stirring, heating to 85-95° C., stirring and refluxing, adding citric acid aqueous solution, stirring and refluxing, centrifuging, washing the precipitate, and then drying to obtain the filler; The primary mixing comprises mixing the filler and ultrapure water and stirring the mixture, controlling the stirring temperature to be 30-50° C., stirring, adding betaine or its salt, stirring, adding hydroxypropyl methylcellulose, stirring, and obtaining a primary coating solution; The method for preparing the secondary coating solution comprises: preparing a supramolecular composition and performing secondary mixing; The method for preparing the supramolecular composition comprises mixing β-cyclodextrin and ultrapure water and stirring the mixture, controlling the stirring temperature to be 25-40° C., stirring, adding an aqueous solution of betaine or a salt thereof, stirring, and spray drying to obtain the supramolecular composition; In the secondary mixing, ethyl cellulose, hydroxypropyl methyl cellulose, triethyl citrate, micropowder silica gel, supramolecular composition and ethanol solution are mixed and stirred, and the stirring temperature is controlled to be 30-50° C., and the secondary coating solution is obtained by stirring.

2. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: The tablet core is prepared by pulverizing angiotensin converting enzyme inhibitor, microcrystalline cellulose, hydroxypropyl methylcellulose mixture, cross-linked polyvinylpyrrolidone and magnesium stearate respectively, and then sieving to obtain the pulverized angiotensin converting enzyme inhibitor, pulverized microcrystalline cellulose, pulverized hydroxypropyl methylcellulose mixture, pulverized cross-linked polyvinylpyrrolidone and pulverized magnesium stearate; the pulverized angiotensin converting enzyme inhibitor, pulverized microcrystalline cellulose, pulverized hydroxypropyl methylcellulose mixture, pulverized cross-linked polyvinylpyrrolidone and ultrapure water are mixed, sieving to prepare wet granules, drying, sieving to prepare whole granules, and then mixing with the pulverized magnesium stearate and tableting to obtain the tablet core.

3. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 2, characterized in that: In the prepared tablet core, the angiotensin converting enzyme inhibitor is one of enalapril, captopril, and benazepril hydrochloride; The hydroxypropyl methylcellulose composition is a mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M, wherein the mass ratio of the mixture of hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose K100M is 1:1-1.2; The mass ratio of the crushed angiotensin converting enzyme inhibitor, crushed microcrystalline cellulose, crushed hydroxypropyl methylcellulose mixture, crushed cross-linked polyvinylpyrrolidone, ultrapure water, and crushed magnesium stearate is 40-45:100-110:45-55:3-4:50-60:24-27; The pressure during tableting is 30-35N.

4. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: In the preparation of the filler, the dosage ratio of hydroxypropyl-β-cyclodextrin, the first portion of ultrapure water, micropowder silica gel, the second portion of ultrapure water, and citric acid aqueous solution is 50-60 g: 1000-1100 mL: 100-110 g: 1000-1100 mL: 550-650 mL; The particle size of the micropowder silica gel is 5 μm; The mass concentration of the citric acid aqueous solution is 20%.

5. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: In the primary mixing, the usage ratio of filler, ultrapure water, betaine or its salt, and hydroxypropyl methylcellulose is 120-130 g: 1000-1100 mL: 45-50 g: 50-55 g; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The betaine or its salt is one of betaine, betaine hydrochloride, betaine phosphate and betaine citrate.

6. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: In the preparation of the supramolecular composition, the dosage ratio of β-cyclodextrin, ultrapure water, and an aqueous solution of betaine or its salt is 9-9.2 g: 500-550 mL: 140-160 mL; The mass concentration of the aqueous solution of betaine or its salt is 20%; The betaine or its salt in the aqueous solution of betaine or its salt is one of betaine, betaine hydrochloride, betaine phosphate and betaine citrate.

7. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: In the secondary mixing, the dosage ratio of ethyl cellulose, hydroxypropyl methyl cellulose, triethyl citrate, micropowder silica gel, supramolecular composition and ethanol solution is 40-43 g: 10-12 g: 10-12 g: 1.8-2 g: 7-8 g: 950-1000 mL; The ethyl cellulose is ethyl cellulose N10; The hydroxypropyl methylcellulose is hydroxypropyl methylcellulose E5; The volume concentration of the ethanol solution is 85%.

8. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: The primary coating comprises placing the tablet core in a fluidized bed coating machine for heat preservation, keeping the temperature constant, and performing a primary coating using a primary coating liquid to obtain a primary coating layer; In the primary coating, the temperature during the heat preservation is 50-55°C, and the heat preservation time is 9-10 minutes; The weight gain of the first coating is 5-5.3%.

9. The method for preparing the betaine composition having a blood pressure lowering effect according to claim 1, characterized in that: The secondary coating comprises placing the primary coating material into a fluidized bed coating machine for heat preservation, maintaining the temperature constant, and performing secondary coating with the secondary coating liquid to obtain a betaine composition having a blood pressure lowering effect; In the secondary coating, the temperature during the heat preservation is 50-55°C, and the heat preservation time is 9-10min; The secondary coating weight gain is 2.8-3%.

10. A betaine composition having a blood pressure lowering effect prepared by the preparation method according to any one of claims 1 to 9.

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