CN115624536A - Medicinal composition for reducing blood pressure, preparation containing same and application - Google Patents

Medicinal composition for reducing blood pressure, preparation containing same and application Download PDF

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CN115624536A
CN115624536A CN202210981539.4A CN202210981539A CN115624536A CN 115624536 A CN115624536 A CN 115624536A CN 202210981539 A CN202210981539 A CN 202210981539A CN 115624536 A CN115624536 A CN 115624536A
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丁锐
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Abstract

The invention belongs to the field of traditional Chinese medicines, and discloses a traditional Chinese medicine preparation for reducing blood pressure.

Description

Pharmaceutical composition for reducing blood pressure, preparation containing pharmaceutical composition and application of pharmaceutical composition
Technical Field
The invention belongs to the field of medicines, and particularly relates to a blood pressure lowering pharmaceutical composition, a preparation containing the same and application thereof.
Background
Hypertension is a systemic disease characterized by an increase in arterial pressure, which may be accompanied by functional or organic changes in organs such as heart, blood vessels, brain and kidneys. Diseases with continuous hypertension can cause diseases such as stroke, heart disease, hemangioma, renal failure and the like. Hypertension is the most common disease with extremely high incidence and growth rate at present, and seriously harms human health.
Nowadays, people also pay more and more attention to the treatment of hypertension. Western medicines are commonly used in the process of treating hypertension, but the long-term use of the synthetic medicines can cause adverse reactions, such as dry cough, dysgeusia, rash, anaphylactic reaction and the like. The Chinese medicine has a long history in China, has the characteristics of multiple targets and multiple effects, and has various effects of removing atherosclerotic plaques, dredging blood vessels, accelerating blood circulation and the like because the Chinese medicine theory considers that a human body is a whole.
At present, the traditional Chinese medicine for treating hypertension only simply compounds traditional Chinese medicinal materials with the function of reducing blood pressure and then decocts, long-time decoction causes drug effect dissipation, and the treatment effect is poor.
CN105616767A discloses a traditional Chinese medicine formula for reducing blood pressure, which comprises, by weight, 5-10 parts of ligusticum chuanxiong hort, 10-15 parts of chrysanthemum, 5-10 parts of rhizoma alismatis, 10-15 parts of astragalus membranaceus, 5-10 parts of selfheal and 10-15 parts of lotus leaves, and the preparation method of the traditional Chinese medicine comprises the following steps: adding water 2-3 times of the total amount of the above materials, decocting for 2-3 hr, and filtering to obtain decoction. The invention has the advantages that: the traditional Chinese medicine composition can effectively reduce blood pressure, light patients can be cured in one course of treatment, heavy patients can be cured in three courses of treatment, the curative effect is remarkable, the recurrence rate is low, and no toxic or side effect exists. The traditional Chinese medicine liquid is not easy to store, and the components with the blood pressure reducing effect are diluted to reduce the curative effect.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a pharmaceutical composition for reducing blood pressure, a preparation containing the pharmaceutical composition and an application of the pharmaceutical composition.
A preparation method of a blood pressure lowering medicine composition comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, then carrying out vacuum drying at 50-60 ℃ and 20-30Pa until the surface is free of water, crushing the dried stevia rebaudiana leaves to 300-600 mu m, then carrying out supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 30-35kg/h, the extraction pressure is 20-25MPa, the primary separation pressure is 6-10MPa, the secondary separation pressure is 4-8MPa, the extraction temperature is 40-60 ℃, the extraction time is 3-5h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried cluster of Prunellae Spica in water at bath ratio of 1g (5-8) mL for 20-40min, cleaning, drying, pulverizing to 0.1-1mm, adding pulverized cluster of Prunellae Spica at bath ratio of 1g (8-12) mL into water, boiling and extracting for 2-3h, filtering to obtain filtrate, repeatedly extracting for 1 time, mixing filtrates for 2 times to obtain cluster of Prunellae Spica extract;
s3, adding 20-40 parts by mass of pressure reducing microspheres into 90-100 parts by mass of the filtrate prepared in the step S2, boiling and assisting with ultrasonic treatment for 20-30min, wherein the ultrasonic power is 600-800W, the frequency is 40-80kHz, then cooling to 60-80 ℃, and carrying out vacuum drying until the water content is 2% -5%, and the vacuum pressure is 20-30Pa to obtain pressure reducing powder;
s4, mixing honey and water according to a mass ratio of (1-2) to (1-2), heating to 70-90 ℃, removing floating foam on the surface of the honey, filtering through a 360-420 mesh gauze, putting the filtered honey into a pot, heating and concentrating until the viscosity is 16-20Pa.s, and obtaining purified honey;
s5, mixing 3-10 parts by mass of stevia rebaudiana leaf extract, 20-40 parts by mass of blood pressure reducing powder and 16-35 parts by mass of purified honey, heating to 40-50 ℃, stirring at the rotating speed of 160-200r/min for 30-40min, and finally preparing into pills with the diameter of 2-3mm to obtain the blood pressure reducing pharmaceutical composition.
The preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, adding 3-10 parts of crassostrea crassipes shell into 100-120 parts of 0.4-0.8wt% hydrochloric acid, adding 3-5 parts of foaming agent, and stirring at the rotating speed of 80-120r/min for 5-10min to obtain a solution A;
n2, crushing 25-35 parts of sea cassia to 100-200 mu m, adding the sea cassia into the solution A prepared in the step N1, continuously stirring at the rotating speed of 80-120r/min, dropwise adding 10-20 parts of 20-30wt% sodium carbonate aqueous solution at the speed of 2-3mL/min, continuously stirring for 3-5min after dropwise adding, standing for 10-20min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded hydrargyrum;
n3 mixing 25-35 parts of the calcium carbonate-loaded hydrargyrum chloratum, 1-3 parts of the modifier, 0.1-1 part of the crosslinking aid and 100-120 parts of water, stirring at 40-60 ℃ at a rotating speed of 80-120r/min for 30-60min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is one or a mixture of two of sodium dodecyl sulfate and disodium ethylene diamine tetraacetate; preferably, the foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of (1-2) to (1-2).
The modifier is one or a mixture of two of glucomannan and isomalto-oligosaccharide; preferably, the modifier is formed by mixing glucomannan and isomalto-oligosaccharide in a mass ratio of (1-2) to (3-5).
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of (1-2) to (5-6).
Stevia rebaudiana, the leaves of which contain rebaudiosides A, B, C, D and E, steviosin A, B, C, D, E, F, G and H, steviol and its glycosides, mainly stevioside, sterols, including stigmasterol, beta-sitosterol, campesterol, and flavonoids and their glycosides. The chrysanthemum glycoside and the glucoside contained in the leaves have various beneficial effects on human bodies: 1. effects on sugar metabolism: stevia component, such as serpentine acid, inhibits sugar synthesis and oxygen absorption in the renal cortex tubule of rat. 2. The blood vessel dilating effect is as follows: stevioside causes a decrease in blood pressure, increased diuresis and natriuresis, increased renal blood flow and glomerular filtration rate in normal or renal hypertensive rats, due in part to arteriolar dilatation. CaCl 2 Can obviously weaken the vasodilatation effect, and indicates that the stevioside can be a calcium mucor mainly through inhibiting Ca 2+ The blood vessel cells are flowed in to promote the blood vessel to expand, thereby achieving the function of reducing blood pressure.
Scylla paramamosain Daldorfia horrida (Linnaeus): shell calcium carbonate (CaCO) 3 ) The crab shell also contains 14 amino acids such as arginine (arginine), aspartic acid (aspartic acid), glutamic acid (glutamic acid), glycine (glycine), alanine (alanine) and the like, and the crab shell is a blood pressure lowering medicine commonly used in traditional Chinese medicine.
Sea cassia seed: is the shell of the Zaocys Spirosoma niger (Gmelin) and the Zaocys Spirosoma russtica (Gmelin) of the California, contains 14 amino acids such as calcium carbonate, arginine, aspartic acid, glutamic acid, glycine, alanine and the like, and has excellent blood pressure lowering effect when being used for the Zaocys Spirospermum.
Prunella vulgaris L: contains triterpenoid saponin, its aglycone is oleanolic acid, and also contains free oleanolic acid, ursolic acid, rutin, alkaloid, water-soluble salt (68% is potassium chloride), and its saponin component also has certain effect of lowering blood pressure.
The invention adopts the carbon dioxide supercritical extraction process, and can effectively extract the effective components of stevioside, stevioside and the like in the stevia rebaudiana. Furthermore, the crab shell of the crab, the crayfish and the sea-ear shell are dissolved in dilute hydrochloric acid, the foaming agent is utilized to combine calcium ions, sea-ear shell micro powder is added into the crab shell, one end of the foaming agent is adsorbed on the sea-ear shell micro powder, and then the calcium carbonate hollow microspheres are obtained on the surface of the sea-ear shell micro powder by utilizing the reaction of carbonate and the calcium ions, so that the calcium carbonate hollow microspheres have higher adsorption capacity. In order to further enhance the adsorption capacity of the sea-ear shell powder and protect the traditional Chinese medicine components from being damaged by gastric acid, glucomannan and isomaltooligosaccharide are further grafted on the surface of the sea-ear shell micro powder loaded with calcium carbonate, and the glucomannan is used as dietary fiber, can not be absorbed, does not contain heat, has satiety and can reduce and delay the absorption of glucose, is a good auxiliary medicine for diabetes mellitus, and can prevent obesity and slowly lose weight; the isomalto-oligosaccharide is difficult to digest by gastric enzyme, has low sweetness and low calorie, does not increase blood sugar and blood fat basically, can promote the proliferation of bifidobacteria in human intestinal tracts, can inhibit the formation of harmful bacteria and putrefactive substances in the intestinal tracts, increases the content of vitamins and improves the immunity of organisms. The two are compounded and grafted on the surface of the sea-ear-cassia micropowder loaded with calcium carbonate, and the long chain and the network formed by the long chain crosslinking greatly increase the adsorption capacity of the sea-ear-cassia micropowder loaded with calcium carbonate, so as to obtain the antihypertensive microspheres with high adsorption performance. Meanwhile, glucomannan and isomaltooligosaccharide are difficult to digest by gastric acid, so that the sustained-release and traditional Chinese medicine components protection effects can be achieved. In addition, because the glucomannan can reduce the absorption of glucose by a human body, the isomaltooligosaccharide is difficult to digest and absorb, the combination of the two can not improve the blood sugar content of the human body, and the composition can be taken by patients with hyperglycemia and hypertension.
The prepared blood pressure reducing microspheres are immersed in the selfheal fruit cluster extracting solution to be completely adsorbed to obtain the blood pressure reducing powder, and the selfheal contains various saponin components, has a certain blood pressure reducing effect, can be used as an adjuvant of a traditional Chinese medicine for reducing blood pressure, and is matched with sea cassia seed to play an excellent blood pressure reducing effect. However, because the blood pressure lowering powder contains calcium carbonate, calcium ions are generated after decomposition by gastric acid, which can promote vasoconstriction and increase blood pressure. Therefore, we further added stevia extract to absorb calcium ions by the high concentration of stevioside therein, preventing it from affecting blood pressure.
The prunella spike extract and the stevia rebaudiana leaf extract contain a large amount of polyphenol substances, and the application of the prunella spike extract and the stevia rebaudiana leaf extract is limited due to low bioavailability in the process of reducing blood pressure. The polylactic acid/glycolic acid copolymer has excellent biocompatibility, good encapsulation, film formation and other characteristics, and can be used as a carrier for delivering the drugs, but the single polylactic acid/glycolic acid copolymer has weak adhesion on intestinal walls, and limits the gastrointestinal retention time of the antihypertensive drugs.
Further preferably, the preparation method of the traditional Chinese medicine preparation for reducing blood pressure comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, then performing vacuum drying at 50-60 ℃ under the condition of 20-30Pa until the surface is free of moisture, crushing the dried stevia rebaudiana leaves to 300-600 mu m, then performing supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 30-35kg/h, the extraction pressure is 20-25MPa, the primary separation pressure is 6-10MPa, the secondary separation pressure is 4-8MPa, the extraction temperature is 40-60 ℃, the extraction time is 3-5h, and after extraction, collecting extracts in a primary separation kettle and a secondary separation kettle, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried cluster of Prunellae Spica in water at bath ratio of 1g (5-8) mL for 20-40min, cleaning, drying, pulverizing to 0.1-1mm, adding pulverized cluster of Prunellae Spica at bath ratio of 1g (8-12) mL into water, boiling and extracting for 2-3h, filtering to obtain filtrate, repeatedly extracting for 1 time, mixing filtrates for 2 times to obtain cluster of Prunellae Spica extract;
s3, adding 20-40 parts by mass of pressure reducing microspheres into 90-100 parts by mass of the filtrate prepared in the step S2, boiling and assisting with ultrasonic treatment for 20-30min, wherein the ultrasonic power is 600-800W, the frequency is 40-80kHz, then cooling to 60-80 ℃, and carrying out vacuum drying until the water content is 2% -5%, and the vacuum pressure is 20-30Pa to obtain pressure reducing powder;
s4, mixing honey and water according to a mass ratio of (1-2) to (1-2), heating to 70-90 ℃, removing floating foam on the surface of the honey, filtering through a 360-420 mesh gauze, putting the filtered honey into a pot, heating and concentrating until the viscosity is 16-20Pa.s, and obtaining purified honey;
s5, mixing 3-10 parts by mass of stevia rebaudiana leaf extract, 20-40 parts by mass of blood pressure reducing powder and 16-35 parts by mass of purified honey, heating to 40-50 ℃, stirring at a rotating speed of 160-200r/min for 30-40min, and finally preparing into pills with the diameter of 2-3mm to obtain the blood pressure reducing pharmaceutical composition;
s6, adding 5-10 parts by mass of the blood pressure reducing pharmaceutical composition into 5-15 parts by mass of water, and uniformly mixing to obtain an aqueous solution of the blood pressure reducing pharmaceutical composition; adding 120-250 parts of polylactic acid/glycolic acid copolymer and 120-250 parts of egg yolk lecithin into 25-50 parts of acetone, and uniformly mixing to obtain polylactic acid/glycolic acid copolymer mixed solution; mixing the blood pressure lowering medicine composition water solution with a polylactic acid/glycollic acid copolymer mixed solution to obtain a mixed solution I; adding 250-500 parts of hydroxypropyl trimethyl ammonium chloride chitosan into 50-100 parts of water, and uniformly mixing to obtain a hydroxypropyl trimethyl ammonium chloride chitosan aqueous solution; adding 500-1000 parts of polyacrylic acid into 100-200 parts of water, and uniformly mixing to obtain a polyacrylic acid aqueous solution; mixing a hydroxypropyl trimethyl ammonium chloride chitosan aqueous solution and a polyacrylic acid aqueous solution, and carrying out ultrasonic treatment for 20-40min, wherein the ultrasonic power is 500-800W, and the ultrasonic frequency is 20-30kHz, so as to obtain a mixed solution II; adding the mixed solution II into the mixed solution I, homogenizing for 15-30min by a homogenizer, magnetically stirring for 12-24h at 1000-2000r/min to obtain emulsion, heating the emulsion to 45-50 ℃, performing rotary evaporation for 10-12h to remove acetone, centrifuging for 30-60min at 2-4 ℃ at 10000-30000r/min, taking precipitate, washing, and freeze-drying to obtain the traditional Chinese medicine preparation for reducing blood pressure.
The inventor utilizes the biocompatibility of the polylactic acid/glycollic acid copolymer and the egg yolk lecithin to easily promote the absorption of the antihypertensive drug, and simultaneously combines the hydroxypropyl trimethyl ammonium chloride chitosan to treat the antihypertensive drug, prolongs the stay of the antihypertensive drug in the gastrointestinal tract cavity, reduces the intestinal clearance mechanism, and increases the interaction with the intestinal epithelium on the absorption surface. The possible reasons for this are: polylactic acid/glycollic acid copolymer, egg yolk lecithin, polyacrylic acid and hydroxypropyl trimethyl ammonium chloride chitosan wrap phenolic compounds through hydrogen bonds and hydrophobic interaction, so that the water solubility of the compounds is increased, and the oxidation in the gastrointestinal tract is prevented. Meanwhile, hydroxypropyl trimethyl ammonium chloride chitosan has positive charges, and epidermal cells and mucosal epithelial cells have negative charges, so that the adhesion of the antihypertensive drug in intestines and stomach is increased through electrostatic interaction, the retention time of the drug is further prolonged, the intestinal clearance mechanism and the interaction with biological targets are reduced, and the intestinal absorption is promoted.
The invention has the beneficial effects that:
the invention discloses a traditional Chinese medicine preparation for reducing blood pressure and a preparation method thereof, which utilizes crab shell of brown shell and sea cassia seed micro powder to prepare sea cassia seed micro powder loaded with calcium carbonate; and the sea cassia tora micro powder loaded with the glucomannan and the isomaltooligosaccharide grafted calcium carbonate is further adopted to obtain the blood pressure reducing microspheres, so that the blood pressure reducing microspheres have good blood pressure reducing effect and adsorbability, and also have the effects of slowly releasing and protecting traditional Chinese medicine components. In order to reduce the effect of calcium ion on vasoconstriction, the blood pressure lowering powder is further mixed with the stevia leaf extract to absorb calcium ion with high concentration of stevioside therein to prevent it from affecting blood pressure. The blood pressure lowering composition is wrapped by polylactic acid/glycollic acid copolymer, yolk lecithin, polyacrylic acid and hydroxypropyl trimethyl ammonium chloride chitosan through hydrogen bond and hydrophobic interaction, so that the retention time of the medicine is prolonged, the intestinal clearance mechanism and the interaction with a biological target are reduced, and the intestinal absorption is promoted.
Detailed Description
Stevia rebaudiana leaf Stevia rebaudiana, purchased from Bailingtang pharmaceutical Co., ltd, bozhou city.
Dried Prunella vulgaris L purchased from Hongzhou Hongbaotang commercial Co., ltd.
Honey, pharmaceutical grade, purchased from Rui Chengkang medicine technology (Shaanxi) Limited.
Rough shell, water chestnut crab shell and sea cassia seed are purchased from the Zhengming Xianjian river diversion area of the Gangxi region to connect with Ming Hui river diversion area of seafood.
Sodium lauryl sulfate, CAS No.: 151-21-3, pharmaceutical grade, purchased from qianli, shan.
Glucomannan, CAS No.: 37220-17-0, food grade, purchased from Nanjing green Biotechnology Ltd.
Isomalto-oligosaccharides, CAS No.: 499-40-1, food grade, purchased from Nanjing green Biotech Ltd.
Polylactic acid/glycolic acid copolymer, polylactic acid glycolic acid =75, molecular weight 30kDa, purchased from lander big handle biotechnology limited, shandong dai handle
Egg yolk lecithin, CAS:93685-90-6, food grade, purchased from Shenzhen Lefu Biotech limited.
Hydroxypropyl trimethyl ammonium chloride chitosan, pharmaceutical grade, purchased from hebei qiansheng biotechnology limited.
Polyacrylic acid, M w =45000, product number: PC04924, purchased from chemical reagents ltd, wungjiang, guangdong.
Example 1
A preparation method of a blood pressure lowering medicine composition comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, then carrying out vacuum drying under the conditions of 55 ℃ and 25Pa until the surface is free of moisture, crushing the dried stevia rebaudiana leaves to 400 mu m, then carrying out supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 32kg/h, the extraction pressure is 25MPa, the primary separation pressure is 8MPa, the secondary separation pressure is 6MPa, the extraction temperature is 50 ℃, the extraction time is 4h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried prunella vulgaris clusters in water according to a bath ratio of 1g to 6mL for 30min, then cleaning, drying and crushing to 0.4mm, then adding the crushed prunella vulgaris clusters in water according to a bath ratio of 1g to 10mL, boiling and extracting for 2h, filtering to obtain filtrate, repeatedly extracting for 1 time, and combining the filtrate for 2 times to obtain an prunella vulgaris cluster extracting solution;
s3, adding 30 parts by mass of pressure-reducing microspheres into 100 parts of the selfheal fruit spike extracting solution prepared in the step S2, boiling, performing ultrasonic treatment for 25min with the ultrasonic power of 700W and the frequency of 60kHz, then cooling to 70 ℃, performing vacuum drying until the water content is 3%, and the vacuum pressure is 25Pa, so as to obtain pressure-reducing powder;
s4, mixing honey and water according to a mass ratio of 1;
s5, mixing 7 parts of stevia rebaudiana leaf extract, 30 parts of blood pressure reducing powder and 24 parts of purified honey in parts by mass, heating to 45 ℃, stirring at a rotating speed of 180r/min for 35min, and finally preparing the mixture into pills with the diameter of 2mm to obtain the blood pressure reducing pharmaceutical composition.
The preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, adding 7 parts of crassocheir sinensis and crab shells into 110 parts of 0.6wt% hydrochloric acid, adding 4 parts of foaming agent, and stirring at the rotating speed of 100r/min for 6min to obtain a solution A;
n2, according to the mass parts, crushing 30 parts of sea cassia to 150 microns, adding the sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 100r/min, then dropwise adding 15 parts of 25wt% sodium carbonate aqueous solution into the solution at the speed of 2mL/min, continuously stirring at the speed of 100r/min for 4min after dropwise adding, then standing for 15min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded sea cassia powder;
and N3, mixing 30 parts by mass of the calcium carbonate-loaded hydrabam starch prepared in the step N2, 2 parts by mass of the modifier, 0.3 part by mass of the crosslinking aid and 110 parts by mass of water, stirring at 50 ℃ at a rotating speed of 100r/min for 40min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of 1.
The modifier is formed by mixing glucomannan and isomaltooligosaccharide according to the mass ratio of 1.
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of 1.
Example 2
A preparation method of a blood pressure lowering medicine composition comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, performing vacuum drying at 55 ℃ and 25Pa until the surface is free of moisture, crushing the dried stevia rebaudiana leaves to 400 mu m, performing supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 32kg/h, the extraction pressure is 25MPa, the primary separation pressure is 8MPa, the secondary separation pressure is 6MPa, the extraction temperature is 50 ℃, the extraction time is 4h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried prunella vulgaris clusters in water according to a bath ratio of 1g to 6mL for 30min, then cleaning, drying and crushing to 0.4mm, then adding the crushed prunella vulgaris clusters in water according to a bath ratio of 1g to 10mL, boiling and extracting for 2h, filtering to obtain filtrate, repeatedly extracting for 1 time, and combining the filtrate for 2 times to obtain an prunella vulgaris cluster extracting solution;
s3, taking the selfheal fruit spike extracting solution prepared in the step S2 by mass, boiling and carrying out ultrasonic treatment for 25min with the ultrasonic power of 700W and the frequency of 60kHz, then cooling to 70 ℃, carrying out vacuum drying until the water content is 3% and the vacuum pressure is 25Pa, and obtaining the pressure reduction powder;
s4, mixing honey and water according to a mass ratio of 1;
s5, mixing 7 parts of stevia rebaudiana leaf extract, 30 parts of blood pressure reducing powder and 24 parts of purified honey according to parts by mass, heating to 45 ℃, stirring at a rotating speed of 180r/min for 35min, and finally preparing the mixture into pills with the diameter of 2mm to obtain the blood pressure reducing pharmaceutical composition.
Example 3
A preparation method of a blood pressure lowering medicine composition comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, then carrying out vacuum drying under the conditions of 55 ℃ and 25Pa until the surface is free of moisture, crushing the dried stevia rebaudiana leaves to 400 mu m, then carrying out supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 32kg/h, the extraction pressure is 25MPa, the primary separation pressure is 8MPa, the secondary separation pressure is 6MPa, the extraction temperature is 50 ℃, the extraction time is 4h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, mixing honey and water according to a mass ratio of 1;
s3, mixing 7 parts of stevia rebaudiana leaf extract, 30 parts of antihypertensive microspheres and 24 parts of purified honey in parts by mass, heating to 45 ℃, stirring at a rotating speed of 180r/min for 35min, and finally preparing the mixture into pills with the diameter of 2mm to obtain the antihypertensive medicinal composition.
The preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, taking 7 parts of crassostrea mollissima shell, crushing the crassostrea mollissima shell into 400 meshes, then adding 110 parts of 0.6wt% hydrochloric acid, adding 4 parts of foaming agent, stirring at the rotating speed of 100r/min for 6min, and filtering to obtain a solution A;
n2, according to the mass parts, crushing 30 parts of sea cassia to 150 microns, adding the sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 100r/min, dropwise adding 15 parts of 25wt% sodium carbonate aqueous solution at the speed of 2mL/min, continuously stirring for 4min after dropwise adding, standing for 15min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded Hadaming powder;
and N3, mixing 30 parts by mass of the calcium carbonate-loaded hydrabam starch prepared in the step N2, 2 parts by mass of the modifier, 0.3 part by mass of the crosslinking aid and 110 parts by mass of water, stirring at 50 ℃ at a rotating speed of 100r/min for 40min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of 1.
The modifier is formed by mixing glucomannan and isomaltooligosaccharide according to the mass ratio of 1.
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of 1.
Example 4
Essentially the same as example 1, except that:
the preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, adding 7 parts of crassocheir sinensis and crab shells into 110 parts of 0.6wt% hydrochloric acid, adding 4 parts of foaming agent, and stirring at the rotating speed of 100r/min for 6min to obtain a solution A;
n2, according to the mass parts, crushing 30 parts of sea cassia to 150 microns, adding the crushed sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 100r/min, dropwise adding 15 parts of 25wt% sodium carbonate aqueous solution into the solution at the speed of 2mL/min, continuously stirring for 4min after dropwise adding, then standing for 15min, centrifuging to obtain precipitate, washing and drying to obtain the calcium carbonate loaded Haiteming powder;
and N3, mixing 30 parts by mass of the calcium carbonate-loaded hydrabam starch prepared in the step N2, 2 parts by mass of the modifier, 0.3 part by mass of the crosslinking aid and 110 parts by mass of water, stirring at 50 ℃ at a rotating speed of 100r/min for 40min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of 1.
The modifier is glucomannan.
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of 1.
Example 5
Essentially the same as example 1, except that:
the preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, adding 7 parts of crassostrea mollissima shell into 110 parts of 0.6wt% hydrochloric acid, adding 4 parts of foaming agent, and stirring at the rotating speed of 100r/min for 6min to obtain a solution A;
n2, according to the mass parts, crushing 30 parts of sea cassia to 150 microns, adding the sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 100r/min, dropwise adding 15 parts of 25wt% sodium carbonate aqueous solution at the speed of 2mL/min, continuously stirring for 4min after dropwise adding, standing for 15min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded Hadaming powder;
and N3, mixing 30 parts by mass of the calcium carbonate-loaded hydrabam starch prepared in the step N2, 2 parts by mass of the modifier, 0.3 part by mass of the crosslinking aid and 110 parts by mass of water, stirring at 50 ℃ at a rotating speed of 100r/min for 40min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of 1.
The modifier is isomalto-oligosaccharide.
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of 1.
Test example 1
The influence of the antihypertensive drug composition prepared in each example on the blood pressure of a hypertensive rat is verified, and the specific steps are as follows:
1. spontaneous hypertensive rats were purchased from Elmante technologies, inc., suzhou Industrial park, 9-11 weeks old, male, 280-320g in body weight, and over 180mmHg in blood pressure;
2. the spontaneous hypertensive rats were housed in 6 groups of 5 rats each, with 12 hours of light circulation at 22 ℃ with the same food and water;
3. feeding the antihypertensive drug composition prepared in the example, one example for each group, 1g per mouse, 3 times per day;
4. the mean values of systolic blood pressure were measured for each group of hypertensive rats on days 0, 4 and 8, respectively, and all results were performed in triplicate. The test results are shown in Table 1.
Table 1: blood pressure measurement of mice
Day 0/mmHg Day 4/mmHg Day 8/mmHg
Example 1 200 167 141
Example 2 198 179 166
Example 3 199 177 162
Example 4 200 171 148
Example 5 199 172 151
As can be seen from table 1, the antihypertensive pharmaceutical composition prepared in example 1 exhibits the best antihypertensive effect. The blood pressure reducing pharmaceutical compositions prepared in example 2 and example 3 have similar effects and are weaker than those prepared in example 1, which indicates that the blood pressure reducing capability of a single prunella spike extract or blood pressure reducing microsphere is weaker because the blood pressure reducing effect of the prunella spike extract is not obvious at all and is mostly used as an adjuvant of a blood pressure reducing traditional Chinese medicine, but the prunella spike extract and sea cassia seed have a synergistic effect and have an excellent blood pressure reducing effect. The antihypertensive drug compositions prepared in examples 4 and 5 also showed excellent antihypertensive effects, but were slightly lower than those of example 1, and were different from example 1 in that the antihypertensive microsphere modifier used in example 4 was glucomannan and the antihypertensive microsphere modifier used in example 5 was isomalto-oligosaccharide. This shows that the combination of glucomannan and isomalto-oligosaccharide has synergistic effect. Because the glucomannan and the isomaltooligosaccharide can form a cross-linked network on the surface of the pressure-reducing microspheres, the adsorption performance is increased, more selfheal fruit spike extracting solution can be retained, and meanwhile, the glucomannan and the isomaltooligosaccharide cooperate to have better protection effect on the traditional Chinese medicine components.
Test example 2
The clinical use effect test of the antihypertensive drug composition prepared in the embodiment comprises the following specific steps:
150 male hypertensive patients were selected and divided into 6 groups of 25 persons each having a systolic blood pressure of 180-190mmHg supplied with the same food and water except that the antihypertensive pharmaceutical compositions prepared in examples 1-6 were administered to each group 3 times a day at 5g each time.
The mean values of systolic blood pressure were measured for each group of volunteers on days 0, 4 and 8, respectively, and all results were performed in triplicate. The test results are shown in Table 2.
Table 2: results of clinical trials
Day 0/mmHg Day 4/mmHg Day 8/mmHg
Example 1 186 139 123
Example 2 188 158 148
Example 3 187 156 146
Example 4 186 145 129
Example 5 188 147 131
Test example 2 is a clinical test, and as can be seen from table 2, the results thereof are consistent with those of the test examples, and example 1 shows an extremely excellent blood pressure lowering effect. The crab shell of the crab, the crayfish and the shell are dissolved in dilute hydrochloric acid, the foaming agent is utilized to combine calcium ions, sea-cassia micro powder is added into the crab shell, one end of the foaming agent is adsorbed on the sea-cassia micro powder, and then the calcium carbonate hollow microspheres are obtained on the surface of the sea-cassia micro powder by utilizing the reaction of carbonate and the calcium ions, so that the calcium carbonate hollow microspheres have higher adsorption capacity. In order to further enhance the adsorption capacity and protect the traditional Chinese medicine components from being damaged by gastric acid, the invention further grafts glucomannan and isomaltooligosaccharide on the surface of the sea-ear-cassia micro powder loaded by calcium carbonate, the two are compounded and grafted on the surface of the sea-ear-cassia micro powder loaded by calcium carbonate, and the long chain and the network formed by the long chain crosslinking greatly increase the adsorption capacity of the sea-ear-cassia micro powder loaded by calcium carbonate, thereby obtaining the pressure-reducing microspheres with high adsorption performance. Meanwhile, glucomannan and isomaltooligosaccharide are difficult to digest by gastric acid, so that the sustained-release and traditional Chinese medicine components protection effects can be achieved.
The prepared blood pressure reducing microspheres are immersed in the selfheal fruit cluster extracting solution to be completely adsorbed to obtain the blood pressure reducing powder, and the selfheal contains various saponin components, has a certain blood pressure reducing effect, can be used as an adjuvant of a traditional Chinese medicine for reducing blood pressure, and is matched with sea cassia seed to play an excellent blood pressure reducing effect. However, because the blood pressure reducing powder contains calcium carbonate, calcium ions are generated after the blood pressure reducing powder is decomposed by gastric acid, so that the blood pressure reducing powder can promote vasoconstriction and increase blood pressure. Therefore, the stevia rebaudiana extract is further added, the stevioside in the stevia rebaudiana extract is a calcium mucoid, the blood pressure is reduced by mainly inhibiting Ca < 2+ > from flowing into blood vessel cells and promoting blood vessel expansion, and the high-concentration stevioside in the stevia rebaudiana extract absorbs calcium ions to prevent the calcium ions from influencing blood pressure. The stevia rebaudiana extract, the selfheal fruit cluster extracting solution and the blood pressure reducing microspheres act together, so that the prepared blood pressure reducing pharmaceutical composition shows an excellent blood pressure reducing effect.
Test example 3
And (3) testing the blood sugar reducing capability: the influence of the antihypertensive medicinal composition prepared by the embodiments of the invention on the blood sugar of a human body is tested according to WS/T652-2019 food glycemic index determination method. 160 individuals with ages of 18-60 years, male and female halves, non-pregnant women and lactating mothers were selected, and the Body Mass Index (BMI, body Mass Index) was within the normal range (18.5 kg/m) 2 -24.0kg/m 2 ) Healthy adults who have no history of diabetes or impaired glucose tolerance, no other metabolic diseases, digestive system diseases, endocrine system diseases, mental diseases and the like, no history of allergy and intolerance to food to be tested and can tolerate fasting state for at least 10h are taken as subjects; 10 subjects were set up for each test group. 80g of cooked rice and 3g of the antihypertensive drug composition prepared by the embodiments of the present invention were used as foods to be tested for each test; the food to be tested of a group of control groups is only 80g of cooked rice and 3g of distilled water, and the antihypertensive medicinal composition is not added.
The measurement cycle comprised six independent test-feeding measurements, with 3 times for the test food (80 g of cooked rice and 3g of the antihypertensive pharmaceutical composition prepared according to the various embodiments of the present invention) and 3 times for the reference food (80 g of cooked rice and 3g of distilled water); the interval of each independent test food measurement is 72h, and the food to be measured is arranged between two reference food measurements; measuring regular work and rest normal diet of the testee in the first three days; the evening meal on the day before the measurement avoids high dietary fiber and high sugar food, and fasting is started before 22; measuring early morning to avoid strenuous exercise, and standing for 10min before the test subject begins to test; separating for 5min, and collecting 2 times of fasting blood samples; starting to eat, wherein all the test substances and water are eaten within 10min, and timing is started from the first eating time; collecting blood sample 30min after meal; the collected part is fingertip capillary blood, the blood-collecting part is kept consistent in the measuring period, and the blood-collecting quantity is 1mL; blood glucose values were measured immediately after blood sample collection and averaged. The results are shown in Table 3.
Table 3: blood sugar level measurement result
Blood glucose Change value (mmol/L) after meal 30min
Example 1 2.6
Example 4 2.9
Example 5 3.1
Control group 4.4
As can be seen from Table 3, the blood glucose change values of the volunteers corresponding to example 1 are the smallest, and the blood glucose change values of the volunteers corresponding to examples 2, 4 and 5 are all smaller than those of the control group, so that the combination of glucomannan and isomalto-oligosaccharide can be demonstrated to have the blood glucose reducing effect. Because the glucomannan is used as dietary fiber, is not absorbed, does not contain heat, has satiety, can reduce and delay the absorption of glucose, is a good auxiliary medicament for diabetes, and can prevent obesity and slowly lose weight; the isomalto-oligosaccharide is difficult to digest by gastric enzyme, has low sweetness and low calorie, does not increase blood sugar and blood fat basically, can promote the proliferation of bifidobacteria in human intestinal tracts, can inhibit the formation of harmful bacteria and putrefactive substances in the intestinal tracts, increases the content of vitamins and improves the immunity of organisms. The two are compounded and grafted on the surface of the sea-ear-cassia micropowder loaded with calcium carbonate, and the long chain and the network formed by the long chain crosslinking greatly increase the adsorption capacity of the sea-ear-cassia micropowder loaded with calcium carbonate, so as to obtain the antihypertensive microspheres with high adsorption performance. Meanwhile, glucomannan and isomaltooligosaccharide are difficult to digest by gastric acid, so the sustained-release preparation can play a role in slowly releasing and protecting traditional Chinese medicine components. In addition, because the glucomannan can reduce the absorption of glucose by a human body, the isomaltooligosaccharide is difficult to digest and absorb, the combination of the two can not improve the blood sugar content of the human body, and the composition can be taken by patients with hyperglycemia and hypertension.
Example 6
A preparation method of a traditional Chinese medicine preparation for reducing blood pressure comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, performing vacuum drying at 55 ℃ and 25Pa until the surface is free of moisture, crushing the dried stevia rebaudiana leaves to 400 mu m, performing supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 32kg/h, the extraction pressure is 25MPa, the primary separation pressure is 8MPa, the secondary separation pressure is 6MPa, the extraction temperature is 50 ℃, the extraction time is 4h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried prunella vulgaris clusters in water according to a bath ratio of 1g to 6mL for 30min, then cleaning, drying and crushing to 0.4mm, then adding the crushed prunella vulgaris clusters in water according to a bath ratio of 1g to 10mL, boiling and extracting for 2h, filtering to obtain filtrate, repeatedly extracting for 1 time, and combining the filtrate for 2 times to obtain an prunella vulgaris cluster extracting solution;
s3, adding 30 parts by mass of pressure-reducing microspheres into 100 parts of the selfheal fruit spike extracting solution prepared in the step S2, boiling, performing ultrasonic treatment for 25min with the ultrasonic power of 700W and the frequency of 60kHz, then cooling to 70 ℃, performing vacuum drying until the water content is 3%, and the vacuum pressure is 25Pa, so as to obtain pressure-reducing powder;
s4, mixing honey and water according to a mass ratio of 1;
s5, mixing 7 parts of stevia rebaudiana leaf extract, 30 parts of blood pressure reducing powder and 24 parts of purified honey in parts by mass, heating to 45 ℃, stirring at a rotating speed of 180r/min for 35min, and finally preparing the mixture into pills with the diameter of 2mm to obtain the blood pressure reducing pharmaceutical composition;
s6, adding 10 parts by mass of the antihypertensive drug composition into 15 parts by mass of water, and uniformly mixing to obtain an aqueous solution of the antihypertensive drug composition; adding 250 parts of PLGA and 250 parts of egg yolk lecithin into 25 parts of acetone, and uniformly mixing to obtain a polylactic acid/glycolic acid copolymer mixed solution; mixing the blood pressure lowering medicine composition water solution with a polylactic acid/glycollic acid copolymer mixed solution to obtain a mixed solution I; adding 500 parts of hydroxypropyl trimethyl ammonium chloride chitosan into 50 parts of water, and uniformly mixing to obtain a hydroxypropyl trimethyl ammonium chloride chitosan aqueous solution; adding 1000 parts of polyacrylic acid into 200 parts of water, and uniformly mixing to obtain a polyacrylic acid aqueous solution; mixing a hydroxypropyl trimethyl ammonium chloride chitosan aqueous solution and a polyacrylic acid aqueous solution, and carrying out ultrasonic treatment for 20min, wherein the ultrasonic power is 500W, and the ultrasonic frequency is 20kHz to obtain a mixed solution II; adding the mixed solution II into the mixed solution I, homogenizing for 30min by a homogenizer, magnetically stirring for 24h at 1500r/min to obtain emulsion, heating the emulsion to 45 ℃, carrying out rotary evaporation for 12h to remove acetone, centrifuging for 60min at 4 ℃ at 15000r/min, taking the precipitate, washing, and freeze-drying to obtain the traditional Chinese medicine preparation for reducing blood pressure.
The preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, adding 7 parts of crassocheir sinensis and crab shells into 110 parts of 0.6wt% hydrochloric acid, adding 4 parts of foaming agent, and stirring at the rotating speed of 100r/min for 6min to obtain a solution A;
n2, according to the mass parts, crushing 30 parts of sea cassia to 150 microns, adding the sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 100r/min, then dropwise adding 15 parts of 25wt% sodium carbonate aqueous solution into the solution at the speed of 2mL/min, continuously stirring at the speed of 100r/min for 4min after dropwise adding, then standing for 15min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded sea cassia powder;
and N3, mixing 30 parts by mass of the calcium carbonate-loaded hydrabam starch prepared in the step N2, 2 parts by mass of the modifier, 0.3 part by mass of the crosslinking aid and 110 parts by mass of water, stirring at 50 ℃ at a rotating speed of 100r/min for 40min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of 1.
The modifier is formed by mixing glucomannan and isomaltooligosaccharide according to the mass ratio of 1.
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of 1.
Example 7
A preparation method of a traditional Chinese medicine preparation for reducing blood pressure comprises the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, performing vacuum drying at 55 ℃ and 25Pa until the surface is free of moisture, crushing the dried stevia rebaudiana leaves to 400 mu m, performing supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 32kg/h, the extraction pressure is 25MPa, the primary separation pressure is 8MPa, the secondary separation pressure is 6MPa, the extraction temperature is 50 ℃, the extraction time is 4h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried fruit clusters of selfheal into water for 30min according to a bath ratio of 1g;
s3, adding 30 parts by mass of pressure-reducing microspheres into 100 parts of the selfheal fruit-spike extracting solution prepared in the step S2, boiling and assisting with ultrasonic treatment for 25min, wherein the ultrasonic power is 700W, the frequency is 60kHz, then cooling to 70 ℃, carrying out vacuum drying until the water content is 3%, and the vacuum pressure is 25Pa, so as to obtain pressure-reducing powder;
s4, mixing honey and water according to a mass ratio of 1;
s5, mixing 7 parts of stevia rebaudiana leaf extract, 30 parts of pressure-reducing powder and 24 parts of purified honey according to parts by mass, heating to 45 ℃, stirring at a rotating speed of 180r/min for 35min, and finally preparing the mixture into pills with the diameter of 2mm to obtain the blood pressure-reducing pharmaceutical composition;
s6, adding 10 parts by mass of the antihypertensive medicinal composition into 15 parts by mass of water, and uniformly mixing to obtain an aqueous solution of the antihypertensive medicinal composition; adding 250 parts of PLGA into 25 parts of acetone, and uniformly mixing to obtain a polylactic acid/glycolic acid copolymer solution; mixing the blood pressure lowering medicine composition water solution with a polylactic acid/glycollic acid copolymer mixed solution to obtain a mixed solution I; adding 1000 parts of polyacrylic acid into 200 parts of water, and uniformly mixing to obtain a polyacrylic acid aqueous solution; mixing polyacrylic acid aqueous solutions, and carrying out ultrasonic treatment for 20min, wherein the ultrasonic power is 500W, and the ultrasonic frequency is 20kHz, so as to obtain a mixed solution II; adding the mixed solution II into the mixed solution I, homogenizing for 15-30min by a homogenizer, magnetically stirring for 12-24h at 1500r/min to obtain emulsion, heating the emulsion to 45 ℃, performing rotary evaporation for 12h to remove acetone, centrifuging for 60min at 4 ℃ at 15000r/min, taking precipitate, washing, and freeze-drying to obtain the traditional Chinese medicine preparation for reducing blood pressure.
The preparation method of the antihypertensive microspheres comprises the following steps:
n1, according to parts by mass, adding 7 parts of crassocheir sinensis and crab shells into 110 parts of 0.6wt% hydrochloric acid, adding 4 parts of foaming agent, and stirring at the rotating speed of 100r/min for 6min to obtain a solution A;
n2, according to the mass parts, crushing 30 parts of sea cassia to 150 microns, adding the sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 100r/min, then dropwise adding 15 parts of 25wt% sodium carbonate aqueous solution into the solution at the speed of 2mL/min, continuously stirring at the speed of 100r/min for 4min after dropwise adding, then standing for 15min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded sea cassia powder;
and N3, mixing 30 parts by mass of the calcium carbonate-loaded hydrabam starch prepared in the step N2, 2 parts by mass of the modifier, 0.3 part by mass of the crosslinking aid and 110 parts by mass of water, stirring at 50 ℃ at a rotating speed of 100r/min for 40min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
The foaming agent is prepared by mixing sodium dodecyl sulfate and disodium ethylene diamine tetraacetate according to the mass ratio of 1.
The modifier is formed by mixing glucomannan and isomaltooligosaccharide according to the mass ratio of 1.
The crosslinking assistant is formed by mixing acetic acid and ammonium acetate according to the mass ratio of 1.
Test example 4
Measuring the content of stevioside in the perfusion liquid by using a rat in-vivo one-way intestinal perfusion model and adopting an HPLC method, and respectively inspecting
The blood pressure reducing traditional Chinese medicine preparation obtained in the examples and the comparative examples has the effect of promoting intestinal absorption of stevioside.
The test of the rat in vivo one-way intestinal perfusion model was performed according to the following procedure:
s1: clean SD rats weighing 200-240g, male, purchased from Experimental animals center of medical college of southeast university, at 22 s2 deg.C, 50 g soil 5% relative humidity, 12h light/12 h dark, fed standard mouse food, and freely drunk water. The animals were kept for 1 week before the experiment to acclimatize. Rats were randomly divided into 2 groups of 3 rats each;
s2, fasting the rat for 12 hours, freely drinking water, carrying out intraperitoneal injection anesthesia on 1% pentobarbital sodium solution (5 mL/kg), fixing the dorsal position, and keeping the body temperature;
s3: opening abdominal cavity about 3cm along abdominal midline, taking jejunum segment about 10cm, cutting at both ends 1cm away from pylorus, intubating and ligating, washing with 37 deg.C constant temperature physiological saline at flow rate of 5mL/min, emptying physiological saline with air, and installing device;
s4: perfusing with perfusate (fraction is 1%) preheated to 37 deg.C at flow rate of 0.2mL/min for 30min, balancing pipeline and intestine section; the perfusion liquid is composed of 7.78mM glucose, 133mM NaC1, 4.56mM KCI and 1.50mM NaHPO 4 、0.20mM MgCl 2 、16mM NaHCO 3 And 3.33mM CaCl 2 And (4) forming. Preparing perfusion fluid containing the blood pressure reducing traditional Chinese medicine preparation (50 mu g/mL) obtained in the example and the comparative example;
s5, timing, respectively collecting perfusion solutions of 0-15, 15-30, 30-45, 45-60, 60-75, 75-90min, 90-105 and 105-120, weighing, and recording the weight of the perfusion solutions and the collected solution;
s6: at the end of the experiment, the length and inner diameter of the bowel sections were measured.
Measuring the content of stevioside in the perfusion liquid by an HPLC method, and calculating the absorption rate constant Ka of the medicine according to the following formula:
Figure BDA0003798694550000181
wherein C is in Denotes the concentration of steviol glycosides at the inlet end, C out(corrected) Represents the concentration of steviol glycoside at the outlet end; q represents the flow rate (0.2 mL/min) and V represents the volume of the intestinal section.
TABLE 4 intestinal absorption effect of Chinese medicinal preparation for lowering blood pressure
K a /10 -3 min -1
Example 6 348.27
Example 7 332.51
The biocompatibility of the polylactic acid/glycollic acid copolymer and the yolk lecithin is utilized, the absorption of the antihypertensive drug is easily promoted, and the treatment is carried out on the antihypertensive drug by combining the hydroxypropyl trimethyl ammonium chloride chitosan, so that the stay of the antihypertensive drug in the gastrointestinal tract cavity is prolonged, the intestinal clearance mechanism is reduced, and the interaction with the intestinal epithelium on the absorption surface is increased. The possible reasons for this are: polylactic acid/glycollic acid copolymer, egg yolk lecithin, polyacrylic acid and hydroxypropyl trimethyl ammonium chloride chitosan wrap phenolic compounds through hydrogen bonds and hydrophobic interaction, so that the water solubility of the compounds is increased, and the oxidation in the gastrointestinal tract is prevented. Meanwhile, hydroxypropyl trimethyl ammonium chloride chitosan has positive charges, epidermal cells and mucosal epithelial cells have negative charges, and the adhesion of the antihypertensive drug in intestines and stomach is increased through electrostatic interaction, so that the retention time of the drug is further prolonged, the intestinal clearance mechanism and the interaction with biological targets are reduced, and the intestinal absorption is promoted.

Claims (8)

1. The preparation method of the traditional Chinese medicine preparation for reducing blood pressure is characterized by comprising the following steps:
s1, extracting stevia rebaudiana components: cleaning stevia rebaudiana leaves, draining, then carrying out vacuum drying at 50-60 ℃ and 20-30Pa until the surface is free of water, crushing the dried stevia rebaudiana leaves to 300-600 mu m, then carrying out supercritical carbon dioxide extraction on the crushed stevia rebaudiana leaves, wherein the flow rate of carbon dioxide is 30-35kg/h, the extraction pressure is 20-25MPa, the primary separation pressure is 6-10MPa, the secondary separation pressure is 4-8MPa, the extraction temperature is 40-60 ℃, the extraction time is 3-5h, collecting extracts in a primary separation kettle and a secondary separation kettle after extraction, and combining to obtain a stevia rebaudiana leaf extract;
s2, selfheal component extraction: soaking dried cluster of Prunellae Spica in water at bath ratio of 1g (5-8) mL for 20-40min, cleaning, drying, pulverizing to 0.1-1mm, adding pulverized cluster of Prunellae Spica at bath ratio of 1g (8-12) mL into water, boiling and extracting for 2-3h, filtering to obtain filtrate, repeatedly extracting for 1 time, mixing filtrates for 2 times to obtain cluster of Prunellae Spica extract;
s3, adding 20-40 parts by mass of pressure reducing microspheres into 90-100 parts by mass of the filtrate prepared in the step S2, boiling and assisting with ultrasonic treatment for 20-30min, wherein the ultrasonic power is 600-800W, the frequency is 40-80kHz, then cooling to 60-80 ℃, and carrying out vacuum drying until the water content is 2% -5%, and the vacuum pressure is 20-30Pa to obtain pressure reducing powder;
s4, mixing honey and water according to a mass ratio of (1-2) to (1-2), heating to 70-90 ℃, removing floating foam on the surface of the honey, filtering through a 360-420-mesh gauze, putting the filtered honey into a pot, heating and concentrating until the viscosity is 16-20Pa.s, and obtaining purified honey;
s5, mixing 3-10 parts by mass of stevia rebaudiana leaf extract, 20-40 parts by mass of blood pressure reducing powder and 16-35 parts by mass of purified honey, heating to 40-50 ℃, stirring at the rotating speed of 160-200r/min for 30-40min, and finally preparing the mixture into pills with the diameter of 2-3mm to obtain the blood pressure reducing pharmaceutical composition;
s6, adding 5-10 parts by mass of the blood pressure reducing pharmaceutical composition into 5-15 parts by mass of water, and uniformly mixing to obtain an aqueous solution of the blood pressure reducing pharmaceutical composition; adding 120-250 parts of polylactic acid/glycolic acid copolymer into 25-50 parts of acetone, and uniformly mixing to obtain a polylactic acid/glycolic acid copolymer aqueous solution; mixing the blood pressure lowering medicine composition water solution with a polylactic acid/glycollic acid copolymer water solution to obtain a mixed solution I; adding 500-1000 parts of polyacrylic acid into 100-200 parts of water, and uniformly mixing to obtain a polyacrylic acid aqueous solution; mixing polyacrylic acid aqueous solution, and performing ultrasonic treatment for 20-40min, wherein the ultrasonic power is 500-800W, and the ultrasonic frequency is 20-30kHz, so as to obtain mixed solution II; adding the mixed solution II into the mixed solution I, homogenizing for 15-30min by a homogenizer, magnetically stirring for 12-24h at 1000-2000r/min to obtain emulsion, heating the emulsion to 45-50 ℃, rotatably steaming for 10-12h to remove acetone, centrifuging for 30-60min at 2-4 ℃ at 10000-30000r/min, taking precipitate, washing, and freeze-drying to obtain the traditional Chinese medicine preparation for reducing blood pressure.
2. The preparation method of the antihypertensive traditional Chinese medicine preparation according to claim 1, wherein step S6 is to add 5 to 10 parts by weight of the antihypertensive drug composition to 5 to 15 parts by weight of water and mix them uniformly to obtain an aqueous solution of the antihypertensive drug composition; adding 120-250 parts of polylactic acid/glycolic acid copolymer and 120-250 parts of egg yolk lecithin into 25-50 parts of acetone, and uniformly mixing to obtain polylactic acid/glycolic acid copolymer mixed solution; mixing the blood pressure reducing medicine composition water solution with the polylactic acid/glycollic acid copolymer mixed solution to obtain a mixed solution I; adding 250-500 parts of hydroxypropyl trimethyl ammonium chloride chitosan into 50-100 parts of water, and uniformly mixing to obtain a hydroxypropyl trimethyl ammonium chloride chitosan aqueous solution; adding 500-1000 parts of polyacrylic acid into 100-200 parts of water, and uniformly mixing to obtain a polyacrylic acid aqueous solution; mixing a hydroxypropyl trimethyl ammonium chloride chitosan aqueous solution and a polyacrylic acid aqueous solution, and carrying out ultrasonic treatment for 20-40min, wherein the ultrasonic power is 500-800W, and the ultrasonic frequency is 20-30kHz, so as to obtain a mixed solution II; adding the mixed solution II into the mixed solution I, homogenizing for 15-30min by a homogenizer, magnetically stirring for 12-24h at 1000-2000r/min to obtain emulsion, heating the emulsion to 45-50 ℃, rotatably steaming for 10-12h to remove acetone, centrifuging for 30-60min at 2-4 ℃ at 10000-30000r/min, taking precipitate, washing, and freeze-drying to obtain the traditional Chinese medicine preparation for reducing blood pressure.
3. The preparation method of the traditional Chinese medicine preparation for reducing blood pressure as claimed in claim 1, wherein the preparation method of the microspheres for reducing blood pressure comprises the following steps: mixing the water chestnut crab shell, the hydrochloric acid, the sea damming powder, the modifier and the water, and filtering, washing and drying to obtain the antihypertensive microspheres.
4. The preparation method of the traditional Chinese medicine preparation for reducing blood pressure as claimed in claim 3, wherein the preparation method of the microspheres for reducing blood pressure comprises the following steps:
n1, according to the mass parts, 3-10 parts of crassocheir sinensis crab shell are added into 100-120 parts of 0.4-0.8wt% hydrochloric acid, 3-5 parts of foaming agent are added into the mixture, and the mixture is stirred for 5-10min at the rotating speed of 80-120r/min to obtain solution A;
n2, according to the mass parts, crushing 25-35 parts of sea cassia to 100-200 mu m, adding the sea cassia into the solution A prepared in the step N1, continuously stirring and stirring at the rotating speed of 80-120r/min, then dropwise adding 10-20 parts of 20-30wt% sodium carbonate aqueous solution at the speed of 2-3mL/min, continuously stirring for 3-5min after dropwise adding, then standing for 10-20min, centrifuging, taking precipitate, washing and drying to obtain calcium carbonate-loaded Hadaming powder;
and N3, mixing 25-35 parts by mass of the hydrargyri oxydum rubrum loaded by the calcium carbonate prepared in the step N2, 1-3 parts by mass of the modifier, 0.1-1 part by mass of the crosslinking aid and 100-120 parts by mass of water, stirring at the rotating speed of 80-120r/min at the temperature of 40-60 ℃ for 30-60min, and then filtering, washing and drying to obtain the pressure-reducing microspheres.
5. The method for preparing a Chinese medicinal preparation for lowering blood pressure as claimed in claim 4, wherein the foaming agent is one or a mixture of two of sodium dodecyl sulfate and disodium edetate.
6. The method for preparing the traditional Chinese medicine preparation for lowering blood pressure as claimed in claim 3 or 4, wherein the modifier is one or a mixture of two of glucomannan and isomalto-oligosaccharide.
7. The method for preparing the traditional Chinese medicine preparation for lowering blood pressure as claimed in claim 4, wherein the cross-linking auxiliary agent is a mixture of acetic acid and ammonium acetate in a mass ratio of (1-2) to (5-6).
8. A Chinese medicinal preparation for lowering blood pressure, which is characterized by being prepared by the preparation method of the Chinese medicinal preparation for lowering blood pressure of any one of claims 1 to 7.
CN202210981539.4A 2022-08-15 2022-08-15 Medicinal composition for reducing blood pressure, preparation containing same and application Withdrawn CN115624536A (en)

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