CN113786430A

CN113786430A - Traditional Chinese medicine extract for reducing blood pressure and preparation method thereof

Info

Publication number: CN113786430A
Application number: CN202111175800.3A
Authority: CN
Inventors: 李兵锁; 李杨; 曹丽华
Original assignee: Shanghai Youtong Medicine Technology Co ltd
Current assignee: Shanghai Youtong Medicine Technology Co ltd
Priority date: 2021-10-09
Filing date: 2021-10-09
Publication date: 2021-12-14

Abstract

The invention discloses a traditional Chinese medicine extract for reducing blood pressure and a preparation method thereof, wherein coptis chinensis, eucommia ulmoides, abalone shells, cassia seeds, selfheal, white paeony root and scutellaria baicalensis are taken as main materials for clearing heat and drying damp and purging fire and detoxifying, wild chrysanthemum flowers, dogbane leaves and uncaria are taken as auxiliary materials for calming the liver and soothing the nerves and clearing heat and promoting diuresis, the main materials and the ministerial materials are combined, the heat and the detoxifying are cleared away, the liver is cooled and the eyesight is improved, and the blood pressure is reduced in the middle warmer, so that the effects of clearing heat and drying damp and purging fire and detoxifying are achieved; the formula has the effects of nourishing yin and suppressing yang, and benefiting yin and yang, and the combination of the medicines can treat both symptoms and root causes, and mainly treat the symptoms. The traditional Chinese medicine is scientific in compatibility, is prepared by adopting a modern scientific preparation process, has an excellent blood pressure reducing effect, can effectively relieve hypertension caused by the fact that the air in the body is abundant due to liver and kidney disorder, yin deficiency and yang excess and water retention, and further relieves dizziness and tinnitus, head and eye distending pain and red face and ear due to hypertension.

Description

Traditional Chinese medicine extract for reducing blood pressure and preparation method thereof

Technical Field

The invention relates to the technical field of preparation or treatment of traditional Chinese medicines, in particular to a traditional Chinese medicine extract for reducing blood pressure and a preparation method thereof.

Background

Hypertension and its complications are an important factor in death and disease worldwide. According to the global hypertension prevalence trend comprehensive analysis report, the number of hypertensive patients in the past 30 years is increased from 6.5 hundred million to 12.8 hundred million all over the world, which accounts for about one sixth of the total population in the world and seriously harms the health of human beings. Hypertension is one of the most common chronic diseases, and is a main factor causing cardiovascular and cerebrovascular diseases, particularly for middle-aged and elderly people. The traditional Chinese medicine has natural advantages in treating hypertension, has holism concept, regards human body as an organic whole, and gives comprehensive consideration to treatment; in addition, the traditional Chinese medicine has the spirit of treatment based on syndrome differentiation, can be used for treating symptoms, can relieve symptoms comprehensively, and can treat symptoms more radically.

Patent 201710197600.5 discloses a Chinese medicinal composition for lowering blood pressure and its preparation method, which is prepared by decocting multiple Chinese medicinal herbs, but the traditional decocting process has the technical problem of less dissolution of effective components of Chinese medicinal herbs, and the utilization rate of raw materials is not high; patent 201410407707.4 provides a Chinese medicinal composition for lowering blood pressure and its preparation method, wherein the Chinese medicinal materials are pulverized into powder by a pulverizer, and the powder is packaged to obtain the Chinese medicinal composition for lowering blood pressure, but the problem of more unwanted impurities in the medicament is easy to occur in the actual production.

Disclosure of Invention

In view of the above-mentioned defects of the prior art, the technical problems solved by the present invention are: (1) the traditional Chinese medicine extract for reducing blood pressure has a good blood pressure reducing effect and a liver protecting effect; (2) the solubility of the active ingredients of the traditional Chinese medicine in the decoction process of the raw materials is increased, and the utilization rate of the raw materials is improved.

According to traditional Chinese medicine, hypertension is called liver-yang hyperactivity, and has various causes, and is caused by liver and kidney disorder, yin deficiency and yang hyperactivity and water intolerance, so that internal qi is filled upwards, excessive qi causes excessive fire, excessive qi fire, dizziness, tinnitus, headache, swelling pain of head and eyes and red face and ears during disease development.

The traditional Chinese medicine extract for reducing blood pressure is a self-composing prescription, and achieves the purpose of reducing blood pressure by synergy. The Chinese medicinal composition is mainly prepared from coptis chinensis, eucommia ulmoides, abalone shells, cassia seeds, selfheal, white paeony root and scutellaria baicalensis, and is assisted by wild chrysanthemum flowers, dogbane leaves and uncaria rhynchophylla for calming the liver and soothing the nerves, clearing heat and promoting diuresis, and the main and assistant medicaments are combined for clearing heat and removing toxicity, cooling the liver and improving eyesight, and lowering blood pressure in tonifying so as to play the effects of clearing heat and drying dampness, and purging fire and removing toxicity. In the formula, the coptis chinensis has the effects of clearing heat, eliminating dampness, purging fire and detoxifying; the eucommia bark is sweet in taste and warm in property and can tonify the liver and kidney, strengthen the middle warmer and replenish vital essence; abalone shell is salty in cold property, pacifying liver and subduing yang, clearing liver and improving vision; semen cassiae is bitter and sweet, clears heat and improves eyesight, and moistens intestines and relieves constipation; the selfheal, the bitter and cold of which can clear heat and improve vision, dissipate stagnation and reduce swelling; the bitter acid of the white peony root is used for nourishing blood, regulating menstruation, astringing yin and suppressing sweating; the bitter and cold property of scutellaria root can purge fire and remove toxicity, relieve chest distress and nausea; the auxiliary materials of wild chrysanthemum flower, dogbane leaf and uncaria are used, and the bitter-pungent wild chrysanthemum flower is used for clearing away heat and toxic material, reducing swelling and improving eyesight; the sweet and cold apocynum venetum leaves clear heat and promote diuresis, and relieve palpitation and insomnia, edema and oliguria; the sweet and cool hooked uncaria can extinguish wind, relieve convulsions, clear heat and stop convulsions. The formula has the effects of nourishing yin and suppressing yang, and benefiting yin and yang, and the combination of the medicines can treat both symptoms and root causes, and mainly treat the symptoms.

In order to achieve the purpose, the invention adopts the following technical scheme:

the invention provides a preparation method of a traditional Chinese medicine extract for reducing blood pressure, which comprises the following steps:

s1, weighing 2-4 parts of coptis chinensis, 6-8 parts of eucommia ulmoides, 4-8 parts of concha haliotidis, 10-13 parts of semen cassiae, 9-12 parts of selfheal, 15-20 parts of radix paeoniae alba, 3-7 parts of scutellaria baicalensis, 9-14 parts of wild chrysanthemum, 6-10 parts of dogbane leaves and 3-8 parts of uncaria, cleaning to remove dust impurities on the surfaces of the raw materials, drying at normal temperature for 8-12 hours to obtain dried and impurity-removed raw materials, mixing, crushing and sieving the dried and impurity-removed raw materials to obtain a powdery raw material mixture for later use;

s2, mixing the powdery raw material mixture obtained in the step S1 and water in a mass ratio of 1: (6-12) mixing to obtain a raw material mixed solution, placing the raw material mixed solution in an automatic decoction device, adding a compound cosolvent into the raw material mixed solution, setting two-stage decoction process parameters, wherein the first-stage decoction temperature is 80-90 ℃, the stirring speed is 60-90 rpm, the decoction time is 5-8 min, the second-stage decoction temperature is 50-60 ℃, the stirring speed is 30-45 rpm, the decoction time is 15-25 min, cooling and filtering, collecting filtrate and recovering filter residues, decocting the filter residues again, and mixing the filter residues with water in a mass ratio of 1: (6-12), decocting by using the same two-section decoction procedure, cooling again, filtering, repeatedly recovering filter residues, decocting the filter residues again for 1-2 times, and combining filtrates obtained by filtering for multiple times to obtain a traditional Chinese medicine extracting solution for later use;

s3, placing the traditional Chinese medicine extracting solution obtained in the step S2 into automatic concentration equipment, and concentrating the traditional Chinese medicine extracting solution at low temperature under reduced pressure until the water content is 15-20 wt% to obtain thick traditional Chinese medicine extract, wherein the thick traditional Chinese medicine extract is the traditional Chinese medicine extract for reducing blood pressure.

In long-term production practice, the inventor finds that the preparation of the traditional Chinese medicine extract by using a decoction method is a method with low cost and relatively simple and convenient operation, but in the process of preparing the traditional Chinese medicine extract for lowering blood pressure by using the method, the technical problem that active ingredients in traditional Chinese medicines are difficult to be fully dissolved in water exists, the solubility of the common active ingredients such as ketone, phenol, alkaloid and the like in raw materials in water is limited, and thus, an optimized space exists in the use of the raw materials.

Therefore, the inventor uses the compound cosolvent prepared by L-arginine, calcium saccharin and nicotinamide in a specific ratio to increase the solubility of the traditional Chinese medicine active ingredients in water. L-arginine and nicotinamide can be combined with phenolic hydroxyl group of ketone substances such as flavone to form soluble intermolecular complex in water; the saccharin calcium can be combined with alkaloid such as berberine in a hydrogen bond complexing mode, so that the solubility is increased, in addition, the saccharin calcium is a sweetener with extremely strong sweet taste, the sweetness of a dilute solution of the saccharin calcium can reach 500 times that of cane sugar, and the bitter taste of the traditional Chinese medicine can be improved.

Preferably, the powdery raw material mixture in the step S1 is 40 to 80 mesh.

Preferably, the addition amount of the composite cosolvent in the step S2 is 3-5 wt% of the raw material mixed solution.

In the step S2, the compound cosolvent is at least one of L-arginine, arginine derivatives, saccharin calcium and nicotinamide. Preferably, in the step S2, the composite cosolvent is arginine derivative, calcium saccharin, and nicotinamide in a mass ratio (12-15): (5-8): 1 of the mixture formed.

Preferably, the arginine derivative is any one of L-arginine, L-arginine grafted chitosan oligosaccharide and deoxycholic acid modified L-arginine grafted chitosan oligosaccharide.

The inventor finds that the L-arginine and the nicotinamide can be compounded to achieve a good solubilizing effect, but the synergy between the L-arginine and the saccharin calcium is still to be further improved. The chitosan oligosaccharide has good water solubility, divalent calcium ions exist in saccharin calcium, and the unique structure of the chitosan oligosaccharide enables the chitosan oligosaccharide to be chelated with divalent metal ions. The L-arginine and the chitosan oligosaccharide are combined by a chemical method, the chitosan oligosaccharide structure and the saccharin calcium can improve the synergistic effect of the two through the combination of divalent calcium ions, and the use effect of the compound cosolvent is further improved.

Preferably, the preparation method of the L-arginine grafted chitosan oligosaccharide comprises the following steps:

x1, mixing 1.25-2.5 parts by weight of chitosan oligosaccharide into 100-150 parts by weight of acetic acid aqueous solution with the concentration of 1-2 wt%, stirring and mixing at 240-480 rpm for 30-60 min until the chitosan oligosaccharide is completely dissolved, adding 1-2 mol/L of sodium hydroxide aqueous solution to adjust the pH of the solution to 12-13, standing for 30-60 min, filtering, mixing a filter cake into 40-80 parts by weight of ethanol, mixing at 120-180 rpm for 15-30 min, adding 1-2 mol/L of hydrochloric acid to adjust the pH of the solution to 4.5-6, adding 3-4.5 parts by weight of benzaldehyde, heating to 60-75 ℃, reacting at 120-180 rpm for 4-6 h, cooling to normal temperature, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain I type chitosan oligosaccharide for later use;

x2 mixing the I-type chitosan oligosaccharide obtained in the step X1 with 50-125 parts of dichloromethane, stirring and mixing at the speed of 360-600 rpm for 30-60 min, adding 4.5-9 parts of paratoluensulfonyl chloride and 0.02-0.05 part of 4-dimethylamino pyridine, reacting at 0-4 ℃ for 0.5-1.5 h, turning to normal temperature, continuing to react for 1.5-2 h, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain II-type chitosan oligosaccharide for later use;

and X3, dissolving the II-type chitosan oligosaccharide obtained in the step X2, 4.5-9 parts of L-arginine and 1-1.25 parts of sodium carbonate in 75-125 parts of water, stirring and mixing at the speed of 360-480 rpm for 15-30 min to obtain a reaction solution, reacting the reaction solution at 115-130 ℃ for 8-12 h through a reflux reaction device, cooling to normal temperature, adding 1-2 mol/L hydrochloric acid to adjust the pH of the reaction solution to be neutral, collecting a supernatant, freezing the supernatant at-5-20 ℃ for 1-2 h, and then freezing and drying at-60-80 ℃ for 4-8 h to obtain the L-arginine grafted chitosan oligosaccharide.

The inventor further improves the technology, and finds that a large number of available chemical active groups exist on the surface of the chitosan oligosaccharide molecule, deoxycholic acid is used for surface modification of the chitosan oligosaccharide to increase lipophilicity, and dissolution of active ingredients of traditional Chinese medicines is facilitated, so that the use efficiency of raw materials is further improved.

Preferably, the method for preparing the deoxycholic acid modified L-arginine grafted chitosan oligosaccharide comprises the following steps:

y1, dissolving 0.75-1.5 parts of deoxycholic acid and 0.1-0.15 part of N-hydroxysuccinimide in 25-50 parts of N, N-dimethylformamide by weight, and stirring and mixing at the speed of 180-360 rpm for 15-30 min to obtain a deoxycholic acid raw material solution for later use;

y2, mixing 1.25-2.5 parts of chitosan oligosaccharide in 100-150 parts of acetic acid aqueous solution with the concentration of 1-2 wt%, stirring and mixing at the speed of 240-480 rpm for 30-60 min until the chitosan oligosaccharide is completely dissolved, adding deoxycholic acid raw material liquid obtained in the step Y1, stirring and reacting at the speed of 120-180 rpm for 8-12 h, adding 1-2 mol/L sodium hydroxide aqueous solution to adjust the pH to 12-13, filtering to obtain a filter cake, washing with alcohol and water, and freeze-drying a reaction product at-60-80 ℃ for 4-6 h to obtain deoxycholic acid modified chitosan oligosaccharide for later use;

y3, mixing the deoxycholic acid modified chitosan oligosaccharide obtained in the step Y2 with 40-80 parts of ethanol, mixing for 15-30 min at a stirring speed of 120-180 rpm, adding 1-2 mol/L hydrochloric acid to adjust the pH value of the solution to 4.5-6, adding 3-4.5 parts of benzaldehyde, heating to 60-75 ℃, reacting for 4-6 h at a stirring speed of 120-180 rpm, cooling to normal temperature, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain type III chitosan oligosaccharide for later use;

y4, mixing the III type chitosan oligosaccharide obtained in the step Y3 with 50-125 parts of dichloromethane, stirring and mixing at the speed of 360-600 rpm for 30-60 min, adding 4.5-9 parts of paratoluensulfonyl chloride and 0.02-0.05 part of 4-dimethylamino pyridine, reacting at 0-4 ℃ for 0.5-1.5 h, turning to normal temperature, continuing to react for 1.5-2 h, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain IV type chitosan oligosaccharide for later use;

y5 dissolving the IV-type chitosan oligosaccharide obtained in the step Y4, 4.5-9 parts of L-arginine and 1-1.25 parts of sodium carbonate in 75-125 parts of water, stirring and mixing at the speed of 360-480 rpm for 15-30 min to obtain a reaction solution, reacting the reaction solution at 115-130 ℃ for 8-12 h through a reflux reaction device, cooling to normal temperature, adding 1-2 mol/L hydrochloric acid to adjust the pH of the reaction solution to be neutral, collecting a supernatant, freezing the supernatant at-5-20 ℃ for 1-2 h, and then freezing and drying at-60-80 ℃ for 4-8 h to obtain the deoxycholic acid modified L-arginine grafted chitosan oligosaccharide.

Preferably, the pressure of the low-temperature reduced-pressure concentration in the step S3 is 7.38-9.59 kPa, and the temperature is 40-45 ℃.

The invention also provides an application of the traditional Chinese medicine extract for reducing blood pressure in preparing traditional Chinese medicine for reducing blood pressure, which comprises the following steps: the traditional Chinese medicine extract for reducing blood pressure and pharmaceutical excipients are mixed according to the mass ratio of 1: (1.2-2) mixing and preparing corresponding granules, tablets and pills; or mixing the traditional Chinese medicine extract for reducing blood pressure and water according to a mass ratio of 1: (6-15) mixing the raw materials to prepare a decoction.

Preferably, the pharmaceutical excipients are a mixture formed by mixing any two or more of fillers, binders, disintegrants and lubricants in any suitable ratio, which meet the technical standard in the field.

Preferably, the filler is starch; the adhesive is dextrin; the disintegrating agent is sodium carboxymethyl starch; the lubricant is magnesium stearate.

The introduction and the function of each raw material in the formula of the invention are as follows:

coptis chinensis: rhizoma Coptidis, and Ranunculaceae. Cold in nature and bitter in taste. They enter heart, spleen, stomach, liver, gallbladder and large intestine meridians. Clear heat and dry dampness, purge fire and remove toxicity. Herbs for clearing heat and drying dampness belong to the category of heat-clearing herbs. Contains berberine, methyl berberine, tetrandrine, berberrubine, epiberberine, coptisine, palmatine, jateorhizine, etc. The authenticity of the coptis chinensis can be identified by a nuclear magnetic resonance hydrogen spectrum method. Berberine is the main effective component of Coptidis rhizoma.

Eucommia ulmoides: the name is herba Gei Piloselloidis, cortex Eucommiae, cortex gossypii, cortex Meliae, and dried bark of Eucommiaceae family Eucomia ulmoides Oliv. Sweet in nature and taste, warm. It enters liver and kidney meridians.

Abalone shell: shell of abalone, sea-bottom sea-ear, sea-ear shell, abalone shell, clam shell, abalone shell, etc. Cold in nature and salty in taste. It enters liver meridian. Pacify liver and subdue yang, clear liver heat and improve vision. Belongs to the category of liver-calming and wind-extinguishing herbs. Mainly containing calcium carbonate. Also contains organic substances, small amount of magnesium, iron, silicate, sulfate, phosphate, chloride and trace amount of iodine.

Cassia seed: is named as semen phaseoli radiati, herba Canavaliae Cannabis, semen Cassiae Nomamis, semen Cimicifulae, semen Oroxyli, and mature seed of Cassia obtusifolia L. Slightly cold in nature, bitter and sweet in taste. It enters liver meridian, kidney meridian and large intestine meridian. Clearing heat, improving eyesight, moistening intestine and relaxing bowels. It belongs to deficiency-heat-clearing herbs classified under heat-clearing herbs. Contains free hydroxy anthraquinone derivatives, such as aurantio-obtusin, chrysophanol, emodin, physcion, emodin anthrone, emodin-6-glucoside, obtusin, semen Cassiae, obtusin, obtusifolin, obtusin, etc.

Selfheal: other names are selfheal, club grass, oldenlandia, Tiexiakusu, Tiessen grass, Langerhans, club grass, and ears of Prunella vulgaris L. Cold in nature, pungent and bitter in flavor. It enters liver meridian and gallbladder meridian. Clearing away fire, improving eyesight, dispersing pathogen accumulation, and relieving swelling. It belongs to heat-clearing herbs and herbs of the category below.

White peony root: radix Paeoniae alba, and root of Paeonia lactiflora pall. Slightly cold in nature, bitter and sour in taste. It enters liver and spleen meridians. Calming liver, relieving pain, nourishing blood, regulating menstruation, astringing yin, and arresting sweating. They belong to the category of tonics. Contains paeoniflorin, hydroxy paeoniflorin, benzoylpaeoniflorin, albiflorin, oxypaeoniflorin, paeoniflorin, hederagenin, paeoniflorin ketone, galloyl paeoniflorin, daucostin, beta-sitosterol, paeoniflorin, etc., and the volatile oil mainly contains benzoic acid, paeonol, etc.

Scutellaria baicalensis: herba Camelliae Japonicae root, Scutellariae radix tea, radix Turkii, and dried root of Scutellaria Baicalensis Georgi of Labiatae. Bitter in property and cold in nature. It enters lung, gallbladder, spleen, large intestine and small intestine meridians. Clear heat and dry dampness, purge fire and remove toxicity, stop bleeding, prevent abortion. Can be used for treating chest distress, nausea, damp-heat, dysentery, jaundice, cough due to lung heat, hyperpyrexia, polydipsia, hematemesis, carbuncle, swelling, sore, and threatened abortion.

Wild chrysanthemum flower: is also called as seed of Job's tears, wild Chrysanthemum, senecio scandens, yellow Chrysanthemum, and the head-like inflorescence of L. of Chrysanthemum indicum of Compositae, which is slightly cold in nature, bitter and pungent in taste. It enters heart and liver meridians. Clearing away heat and toxic material, eliminating swelling, cooling liver and improving vision. Belongs to heat-clearing and fire-purging herbs classified under heat-clearing herbs. Contains wild chrysanthemum lactone, wild chrysanthemum alcohol, wild chrysanthemum triol, wild chrysanthemum ketone, etc. The volatile oil mainly contains oxygenated terpene and sesquiterpene, and is a component of flos Chrysanthemi Indici with peculiar fragrance.

And (3) dogbane leaf: is prepared from leaves of plants including flos Carthami, herba Euphorbiae Helioscopiae, herba Giardisiae Japonicae, herba Euphorbiae Helioscopiae, herba Apocyni Veneti of Apocynaceae. Cool in nature, sweet and bitter in taste. It enters liver meridian. Pacify liver, tranquilize mind, clear heat and induce diuresis. Belongs to the category of liver-calming and wind-extinguishing herbs. Contains flavonoids, catechin, anthraquinone, glutamic acid, alanine, valine, potassium chloride, quercetin, rutin, isoquercitrin, D-catechin, hyperoside, lupeol palmitate, myricyl palmitate, scopoletin, and steroid.

Uncaria: ramulus Uncariae cum uncis, and ramulus Uncariae cum uncis of Rubiaceae family, Uncaria thynchhylla (Miq.) Jacks, or Uncaria sinensis (Oliv.) Havil. Cool in nature and sweet in taste. It enters liver meridian and pericardium meridian. Clear heat, calm liver, stop endogenous wind and calm convulsion. Belongs to the category of liver-pacifying and wind-extinguishing herbs and wind-extinguishing and spasm-stopping herbs. Contains alkaloids such as rhynchophylline, isorhynchophylline, hirsutine, and dehydrohirsutine. And other components such as vincoside-lactam, hyperoside, trifolioside, isorhynchophylline, dehydrorhynchophylline, isorhynchophylline IV, oxide, levogyration, epicatechol, scopoletin, etc.

L-arginine: the organic compound has a certain detoxification effect, is a basic composition of various proteins, and has wide existence.

Calcium saccharin: white crystal or white crystalline powder, no nutritive sweetener, and strong sweet taste, and its thin solution has sweetness about 500 times that of sucrose.

Nicotinamide: amide compounds of nicotinic acid, white crystalline powders, are easily soluble in water or ethanol and soluble in glycerol.

Chitosan oligosaccharide: an oligosaccharide product with the polymerization degree of 2-20 obtained by degrading chitosan, the molecular weight of which is less than or equal to 3200Da, and the oligosaccharide product is a low molecular weight product with good water solubility, large functional effect and high biological activity

On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.

The invention has the beneficial effects that:

compared with the prior art, the traditional Chinese medicine composition mainly comprises coptis chinensis, eucommia ulmoides, abalone shells, semen cassiae, selfheal, white paeony root and scutellaria baicalensis, and has the effects of clearing heat, eliminating dampness, purging fire and detoxifying, and the auxiliary materials comprise wild chrysanthemum flower, folium apocyni veneti and uncaria for clearing heat, promoting diuresis, relieving palpitation, insomnia, edema and oliguria, has a good blood pressure reducing effect, is combined with main and ministerial medicines, has the effects of nourishing yin, suppressing yang, and benefiting yin and yang, is combined with various medicines, treats both principal and secondary aspects of diseases, and is mainly used for treating symptoms.

Compared with the prior art, the invention has the effects of calming the liver, soothing the nerves, clearing liver, improving eyesight, relieving yin deficiency and yang hyperactivity, preventing water retention, lowering blood pressure and protecting the liver.

Compared with the prior art, the composite cosolvent used in the invention can increase the dissolution of active ingredients of traditional Chinese medicines, improve the content of the active ingredients in the product and increase the utilization rate of raw materials.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.

Some raw material parameters in the comparative examples and examples of the invention are as follows:

coptis chinensis, full dry tablets, origin: chongqing city;

eucommia ulmoides, whole dry sheet, origin: zhang Jiajie city in Hunan province;

abalone shell, full dry sheet, origin: fujian province, Fuzhou city;

cassia seed, full dry granular, origin: anhui mussel port;

selfheal, full-dry column shape, production area: henan Statema shop;

white peony root, full dry flakes, origin: changde city of Hunan;

scutellaria baicalensis, whole dry tablets, origin: hebei Chengde City;

wild chrysanthemum flower, full dry and granular, production area: sichuan adult cities;

dogbane leaf, full dry sheet, production area: xinjiang Uygur autonomous region;

uncaria, full-dry hooked, producing area: guangxi Guilin City;

l-arginine, hannam polyco biotechnology ltd, CAS no: 74-79-3;

calcium saccharin, eastern Fuwangjia Biotech limited, CAS No.: 6485-34-3;

niacinamide, Shanghai leaf Biotech, Inc., CAS number: 98-92-0;

chitosan oligosaccharide, particle size 120 mesh, Hubei hongtao bioengineering limited, CAS No.: 148411-57-8.

Example 1

A traditional Chinese medicine extract for reducing blood pressure is prepared by the following method:

s1 weighing 30g of coptis chinensis, 70g of eucommia ulmoides, 50g of abalone shell, 110g of semen cassiae, 90g of selfheal, 160g of radix paeoniae alba, 120g of wild chrysanthemum, 80g of dogbane leaf and 40g of radix scutellariae, cleaning to remove dust impurities on the surfaces of the raw materials, drying at normal temperature for 8 hours to obtain dried and impurity-removed raw materials, mixing, crushing and sieving the dried and impurity-removed raw materials with a 40-mesh sieve to obtain a powdery raw material mixture for later use;

s2, mixing the powdery raw material mixture obtained in the step S1 and water in a mass ratio of 1: 8, mixing to obtain a raw material mixed solution, placing the raw material mixed solution in an automatic decoction device, setting two sections of decoction process parameters, wherein the first section decoction temperature is 85 ℃, the stirring speed is 90rpm, and the decoction time is 6min, the second section decoction temperature is 55 ℃, the stirring speed is 30rpm, and the decoction time is 20min, cooling and filtering are carried out, filtrate is collected and filter residue is recovered, re-decoction of the filter residue is carried out, and the filter residue is only decocted with water in a mass ratio of 1: 8, mixing, decocting by using the same two-section decoction procedure, cooling again, filtering, repeatedly recovering filter residue, decocting the filter residue again for 2 times, and mixing filtrates obtained by filtering for multiple times to obtain a traditional Chinese medicine extracting solution for later use;

s3, placing the traditional Chinese medicine extracting solution obtained in the step S2 into automatic concentration equipment, and concentrating at low temperature under reduced pressure until the water content is 18 wt% to obtain a thick traditional Chinese medicine extract, wherein the thick traditional Chinese medicine extract is the traditional Chinese medicine extract for reducing blood pressure.

The pressure of the low-temperature reduced-pressure concentration in the step S3 is 7.38kPa, and the temperature is 40 ℃.

Example 2

Basically in accordance with example 1, the difference is only that in step S1, the raw materials are: 30g of coptis chinensis, 70g of eucommia ulmoides, 50g of concha haliotidis, 110g of semen cassiae, 90g of selfheal, 160g of radix paeoniae alba, 120g of wild chrysanthemum flower, 30g of uncaria and 40g of scutellaria baicalensis.

Example 3

Basically in accordance with example 1, the difference is only that in step S1, the raw materials are: 30g of coptis chinensis, 70g of eucommia ulmoides, 50g of concha haliotidis, 110g of semen cassiae, 90g of selfheal, 160g of radix paeoniae alba, 80g of dogbane leaf, 30g of uncaria and 40g of scutellaria baicalensis.

Example 4

Basically in accordance with example 1, the difference is only that in step S1, the raw materials are: 30g of coptis chinensis, 70g of eucommia ulmoides, 50g of concha haliotidis, 110g of semen cassiae, 90g of selfheal, 160g of radix paeoniae alba, 120g of wild chrysanthemum flower, 80g of dogbane leaf, 30g of uncaria and 40g of scutellaria baicalensis.

Example 5

s1, weighing 30g of coptis chinensis, 70g of eucommia ulmoides, 50g of concha haliotidis, 110g of semen cassiae, 90g of selfheal, 160g of radix paeoniae alba, 120g of wild chrysanthemum flower, 80g of folium apocyni veneti, 30g of uncaria and 40g of scutellaria baicalensis, cleaning to remove dust and impurities on the surfaces of the raw materials, drying at normal temperature for 8 hours to obtain dried and impurity-removed raw materials, mixing, crushing and sieving the dried and impurity-removed raw materials with a 40-mesh sieve to obtain a powdery raw material mixture for later use;

s2, mixing the powdery raw material mixture obtained in the step S1 and water in a mass ratio of 1: 8, mixing to obtain a raw material mixed solution, placing the raw material mixed solution in an automatic decoction device, adding a compound cosolvent into the raw material mixed solution, wherein the addition is 4 wt% of the raw material mixed solution, setting two-stage decoction process parameters, the first-stage decoction temperature is 85 ℃, the stirring speed is 90rpm, the decoction time is 6min, the second-stage decoction temperature is 55 ℃, the stirring speed is 30rpm, the decoction time is 20min, cooling and filtering are carried out, filtrate is collected, filter residue is recovered, re-decoction of the filter residue is carried out, and the filter residue and water are mixed according to the mass ratio of 1: 8, mixing, decocting by using the same two-section decoction procedure, cooling again, filtering, repeatedly recovering filter residue, decocting the filter residue again for 2 times, and mixing filtrates obtained by filtering for multiple times to obtain a traditional Chinese medicine extracting solution for later use;

In the step S2, the compound cosolvent is L-arginine and nicotinamide in a mass ratio of 14: 1 of the mixture formed.

Example 6

Essentially in accordance with example 5, the only difference is that: in the step S2, the composite cosolvent is L-arginine and calcium saccharin according to a mass ratio of 14: 6 of the mixture formed.

Example 7

Essentially in accordance with example 5, the only difference is that: in the step S2, the compound cosolvent is calcium saccharin and nicotinamide in a mass ratio of 6: 1 of the mixture formed.

Example 8

Essentially in accordance with example 5, the only difference is that: in the step S2, the compound cosolvent is L-arginine, calcium saccharin and nicotinamide in a mass ratio of 14: 6: 1 of the mixture formed.

Example 9

In the step S2, the compound cosolvent is L-arginine grafted chitosan oligosaccharide, calcium saccharin and nicotinamide in a mass ratio of 14: 6: 1 of the mixture formed.

The preparation method of the L-arginine grafted chitosan oligosaccharide comprises the following steps:

x1 is prepared by mixing 1.5g of chitosan oligosaccharide in 125g of acetic acid aqueous solution with the concentration of 1 wt%, stirring and mixing at the speed of 360rpm for 45min until the chitosan oligosaccharide is completely dissolved, adding 1mol/L of sodium hydroxide aqueous solution to adjust the pH of the solution to 12, standing for 30min, filtering, mixing a filter cake in 60g of ethanol, mixing at the stirring speed of 180rpm for 15min, adding 1mol/L of hydrochloric acid to adjust the pH of the solution to 5.5, adding 3g of benzaldehyde, heating to 75 ℃, reacting at the stirring speed of 180rpm for 4h, cooling to normal temperature, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain type I chitosan oligosaccharide for later use;

x2 mixing the type I chitosan oligosaccharide obtained in the step X1 with 75g of dichloromethane, stirring and mixing for 45min at the speed of 480rpm, adding 7.5g of paratoluensulfonyl chloride and 0.04g of 4-dimethylaminopyridine, reacting for 1h at 0 ℃, turning to normal temperature to continue reacting for 1.5h, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain type II chitosan oligosaccharide for later use;

and X3, dissolving the type II chitosan oligosaccharide obtained in the step X2, 6g L-arginine and 1g of sodium carbonate in 100g of water, stirring and mixing at the speed of 360 ℃ for 30min to obtain a reaction solution, reacting the reaction solution at 115 ℃ for 10h by using a reflux reaction device, cooling to normal temperature, adding 1mol/L hydrochloric acid to adjust the pH of the reaction solution to be neutral, collecting supernatant, freezing the supernatant at-10 ℃ for 2h, and then freeze-drying at-80 ℃ for 8h to obtain the L-arginine grafted chitosan oligosaccharide.

Example 10

In the step S2, the compound cosolvent is deoxycholic acid modified L-arginine grafted chitosan oligosaccharide, calcium saccharin and nicotinamide in a mass ratio of 14: 6: 1 of the mixture formed.

The preparation method of the deoxycholic acid modified L-arginine grafted chitosan oligosaccharide comprises the following steps:

y1 is prepared by dissolving 0.75g deoxycholic acid and 0.1g N-hydroxysuccinimide in 30g N, and stirring and mixing N-dimethylformamide at 240rpm for 20min to obtain deoxycholic acid raw material solution for later use;

y2, mixing 1.5g of chitosan oligosaccharide with 125g of acetic acid aqueous solution with the concentration of 1 wt%, stirring and mixing at the speed of 360rpm for 45min until the chitosan oligosaccharide is completely dissolved, adding the deoxycholic acid raw material solution obtained in the step Y1, stirring and reacting at the speed of 180rpm for 8h, adding 1mol/L sodium hydroxide aqueous solution to adjust the pH value to 12, filtering to obtain a filter cake, washing with alcohol and water, and freeze-drying the reaction product at-80 ℃ for 4h to obtain deoxycholic acid modified chitosan oligosaccharide for later use;

y3, mixing the deoxycholic acid modified chitosan oligosaccharide obtained in the step Y2 in 60g of ethanol, mixing for 15min at a stirring speed of 180rpm, adding 1mol/L hydrochloric acid to adjust the pH value of the solution to 5.5, adding 3g of benzaldehyde, heating to 75 ℃, reacting for 4h at a stirring speed of 180rpm, cooling to normal temperature, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain type III chitosan oligosaccharide for later use;

y4 mixing the type III chitosan oligosaccharide obtained in the step Y3 with 75g of dichloromethane, stirring and mixing for 45min at the speed of 480rpm, adding 7.5g of paratoluensulfonyl chloride and 0.04g of 4-dimethylaminopyridine, reacting for 1h at 0 ℃, turning to normal temperature to continue reacting for 1.5h, filtering to obtain a filter cake, washing with alcohol, washing with water, and drying to obtain type IV chitosan oligosaccharide for later use;

y5, dissolving the IV-type chitosan oligosaccharide obtained in the step Y4, 6g L-arginine and 1g of sodium carbonate in 100g of water, stirring and mixing at the speed of 360rpm for 30min to obtain a reaction solution, reacting the reaction solution at 115 ℃ for 10h through a reflux reaction device, cooling to normal temperature, adding 1mol/L hydrochloric acid to adjust the pH of the reaction solution to be neutral, collecting a supernatant, freezing the supernatant at-10 ℃ for 2h, and then freeze-drying at-80 ℃ for 8h to obtain the deoxycholic acid modified L-arginine grafted chitosan oligosaccharide.

Comparative example 1

In substantial agreement with example 1, the only difference is that the formula of the traditional Chinese medicine extract for lowering blood pressure is as follows: 30g of coptis chinensis, 70g of eucommia ulmoides, 50g of abalone shell, 110g of cassia seed, 90g of selfheal, 160g of white paeony root and 40g of scutellaria baicalensis.

Test example 1

The blood pressure reducing effect of the invention is tested, the tested object is SHR male rat with SPF grade and weight of 300-400 g/mouse, the control group selects common male Wistar rat with SPF grade and weight of 300-400 g/mouse, the SHR rat and Wistar rat are provided by Shanghai experimental animal center of Chinese academy of sciences. The test method is carried out according to the specific requirements of spontaneous hypertension rats in the experimental methodology of syndrome differentiation and treatment of rats and mice (Zhaoqin, scientific publishing Co.). Randomly taking 15 Wistar rats as a normal group; randomly taking 15 SHR rats as a model group; 165 SHR rats were randomly assigned to 11 groups of 15 rats each and used as experimental groups. The normal group, the model group and the experimental group were fed with basal diet and water freely daily, and the feeding environment was 25 ℃. The experimental group comprises traditional Chinese medicine extracts and water which are used for reducing blood pressure by intragastric administration every day, wherein the mass ratio of the traditional Chinese medicine extracts to the water is 1: 8 the preparation is prepared into decoction with a dosage of 4mL/10 g.body weight, and is administered continuously for 5 days and stopped for 2 days every week for 4 weeks, and the blood pressure (systolic pressure) of each group of rats is tested every week. The rat blood pressure test was performed using a BP-2010A model animal non-invasive sphygmomanometer (provided by shenzhen, reuwade life science and technology ltd), and the results were averaged by taking multiple numerical values. The measurement results of the blood pressure of the SHR rat are shown in Table 1, and the measurement results have statistical significance.

Table 1: SHR rat blood pressure measurement result table

After the SHR rat takes the traditional Chinese medicine extract for reducing blood pressure, the blood pressure change trend is compared with that of a normal rat and an SHR rat not taking the traditional Chinese medicine, so that the blood pressure reducing effect of different traditional Chinese medicine component embodiments can be reflected, and the blood pressure level approaches to the normal group after the intragastric lavage treatment, which means that the blood pressure reducing effect is better. Compared with the comparative example, the recipe uses coptis chinensis, eucommia ulmoides, abalone shells, cassia seeds, selfheal, white paeony root and scutellaria baicalensis as main materials for clearing heat and drying dampness and purging fire and detoxifying, uses wild chrysanthemum flowers, dogbane leaves and uncaria rhynchophylla for calming the liver and soothing the nerves and clearing heat and inducing diuresis as auxiliary materials, combines the main materials and the ministerial materials, clears heat and detoxifies, cools the liver and improves eyesight, lowers the blood pressure during tonifying, has the effects of clearing heat and drying dampness and purging fire and detoxifying, and can reduce blood pressure and further relieve palpitation, insomnia, edema and oliguria caused by hypertension. The formula has the effects of nourishing yin and suppressing yang, and benefiting yin and yang, and all the medicines are used together to treat both principal and secondary aspects of diseases.

Test example 2

The liver protection effect is achieved by using a mouse drunkenness experiment, the experimental objects are C57BL/6 male mice with the weight of 18-22 g/mouse, and the C57BL/6 male mice are provided by animal experiment research center of Zhejiang Chinese medicine university. After the C57BL/6 male mice are adaptively fed for 1 week, the mice are randomly distributed according to the body mass, 15 normal C57BL/6 male mice are randomly taken as a normal group, 15 normal C57BL/6 male mice are randomly taken as a model group, 165 normal C57BL/6 male mice are randomly taken and divided into 11 groups, and 15 normal C57BL/6 male mice are taken as an experimental group. The establishment of the C57BL/6 mouse alcoholic liver injury model is carried out according to the specific requirements of the establishment of the alcoholic liver injury mouse model in the comparison of the mouse alcoholic liver injury models induced by two different alcohol intake modes (Xiaojuan, China comparison medical journal 2016, volume 26, No. 6). The alcohol adaptation period of the alcohol gavage group is 1 week, the alcohol gavage dosage is gradually increased from 0.5g/kg body weight to 6g/kg body weight, the molding period is 8 weeks, the gavage dosage is 6g/kg body weight after 1-4 weeks, the gavage dosage is 5g/kg body weight after 5-8 weeks, and the distilled water with the same amount as that of the gavage of the normal group is used.

After the alcoholic liver injury mouse is modeled, basal feed is normally fed and water is freely drunk every day, and the feeding environment is 25 ℃. The experimental group comprises traditional Chinese medicine extracts and water which are used for reducing blood pressure by intragastric administration every day, wherein the mass ratio of the traditional Chinese medicine extracts to the water is 1: 8 the decoction is prepared by mixing the components in a dosage of 1mL/10 g.body weight, continuously taking the medicine for 5 days and stopping for 2 days every week, and testing after 4 weeks of treatment. And (3) performing intragastric gavage on the mice by using liquor with the alcohol content of 52 degrees at the concentration of 1.5ml/10 g.body weight, and measuring the whole blood ethanol content of the mice after the intragastric gavage for 0.5h, 1h, 2h and 4h, wherein the reference of the method for measuring the whole blood ethanol of the mice refers to disease animal model research compiled by the ninth regional experimental animal science and technology Commission treatise: the KM mouse drunkenness model and the whole blood ethanol determination are specifically operated, and the average value of the results is calculated by taking a plurality of numerical values. The measurement result of the liver injury mouse drunk whole blood ethanol is shown in table 2, and the measurement result has statistical significance.

Table 2: liver injury mouse drunk whole blood ethanol determination result table

After the mice are infused with gastric alcohol, the alcohol content in blood shows a trend of ascending first and then descending due to the action of absorption and metabolism, and the liver is used as a main metabolic organ of alcohol, and the capacity of the liver to metabolize the alcohol reflects the liver function level. As can be seen from the comparison between the examples and the comparative examples, the recipe has the effects of tonifying middle-jiao and Qi, calming liver and suppressing yang hyperactivity, and clearing liver and improving vision, and can relieve liver function damage to achieve the effect of protecting liver.

Test example 3

The determination of the content of the total flavonoids in the traditional Chinese medicine extract for reducing blood pressure is carried out according to the specific requirements of the test part in the content determination of the total flavonoids in the Guanxinning tablets (Shizhen national medicine, 2005, volume 16, No. 4). The test uses a UV-7504 ultraviolet-visible spectrophotometer (supplied by Beijing Nenke engineering Co., Ltd.) to measure the absorbance at 510nm wavelength and calculate the total flavone content. Weighing the traditional Chinese medicine extract for reducing blood pressure, and preparing five samples in each group, wherein each sample weighs 1.0 g. The results of the total flavone content in the blood pressure lowering herbal extract are shown in table 3.

Table 3: table of results of total flavone content in herb extracts for lowering blood pressure

Test set	Total Flavonoids content (mg/g)
		Example 4	32.4
Example 5	47.1
		Example 6	44.2
Example 7	38.5
		Example 8	51.8
Example 9	55.3
		Example 10	60.7

The preparation of the traditional Chinese medicine extract requires that the content of active ingredients exerting the drug effect in the traditional Chinese medicine is higher, and the extraction efficiency of the preparation process is more excellent. The flavone is an active substance contained in the traditional Chinese medicine, and has the effect of reducing blood pressure. The comparison of the examples shows that the addition of the compound cosolvent can help to improve the dissolution of the flavone in the decoction process, so that the total flavone content of the final finished product is improved. The compound cosolvent composed of the three components selected in the example 10 has the best implementation effect, and the reason may be that the compound cosolvent can be compounded to play a good solubilizing effect, can be combined with ketone substances such as phenolic hydroxyl of flavone to form a soluble intermolecular complex in water, so that the solubility of the flavone in the water is increased, and further, the content of total flavone in a finished product is increased.

Claims

1. A preparation method of a traditional Chinese medicine extract for reducing blood pressure is characterized by comprising the following steps:

s1, weighing 2-4 parts of coptis chinensis, 6-8 parts of eucommia ulmoides, 4-8 parts of abalone shell, 10-13 parts of semen cassiae, 9-12 parts of selfheal, 15-20 parts of radix paeoniae alba, 3-7 parts of scutellaria baicalensis, 9-14 parts of wild chrysanthemum flower, 6-10 parts of dogbane leaf and 3-8 parts of uncaria, cleaning to remove dust and impurities on the surface of the raw materials, drying at normal temperature for 8-12 hours to obtain dried and impurity-removed raw materials, mixing, crushing and sieving the dried and impurity-removed raw materials to obtain a powdery raw material mixture for later use;

s3, carrying out low-temperature reduced pressure concentration on the traditional Chinese medicine extracting solution obtained in the step S2 until the water content is 15-20 wt%, and obtaining a thick traditional Chinese medicine extract, wherein the thick traditional Chinese medicine extract is the traditional Chinese medicine extract for reducing blood pressure.

2. The preparation method of the traditional Chinese medicine extract for reducing blood pressure as claimed in claim 1, is characterized in that: in the step S1, the powdery raw material mixture is 40-80 meshes.

3. The preparation method of the traditional Chinese medicine extract for reducing blood pressure as claimed in claim 1, is characterized in that: the adding amount of the compound cosolvent in the step S2 is 3-5 wt% of the raw material mixed solution.

4. The preparation method of the traditional Chinese medicine extract for reducing blood pressure as claimed in claim 1, is characterized in that: in the step S2, the compound cosolvent is at least one of L-arginine, arginine derivatives, saccharin calcium and nicotinamide.

5. The preparation method of the traditional Chinese medicine extract for reducing blood pressure as claimed in claim 1, is characterized in that: in the step S2, the composite cosolvent is arginine derivative, calcium saccharin and nicotinamide in a mass ratio of (12-15): (5-8): 1 of the mixture formed.

6. The method for preparing the extract of the traditional Chinese medicine for reducing blood pressure as claimed in claim 4 or 5, wherein the method comprises the following steps: the arginine derivative is any one of L-arginine grafted chitosan oligosaccharide and deoxycholic acid modified L-arginine grafted chitosan oligosaccharide.

7. The method for preparing the extract of the traditional Chinese medicine for reducing blood pressure as claimed in claim 6, wherein the method for preparing the L-arginine grafted chitosan oligosaccharide comprises the following steps:

x2 mixing the I-type chitosan oligosaccharide obtained in the step X1 with 50-125 parts of dichloromethane, stirring and mixing at the speed of 360-600 rpm for 30-60 min, adding 4.5-9 parts of tosyl chloride and 0.02-0.05 part of 4-dimethylaminopyridine, reacting at 0-4 ℃ for 0.5-1.5 h, turning to the normal temperature, continuing to react for 1.5-2 h, filtering, washing with alcohol, washing with water, and drying to obtain II-type chitosan oligosaccharide for later use;

8. The preparation method of the traditional Chinese medicine extract for reducing blood pressure as claimed in claim 1, is characterized in that: the pressure of the low-temperature reduced-pressure concentration in the step S3 is 7.38-9.59 kPa, and the temperature is 40-45 ℃.

9. A traditional Chinese medicine extract for reducing blood pressure, which is prepared by the method of any one of claims 1 to 8.

10. The use of the extract of a Chinese medicinal material for lowering blood pressure according to claim 9 in the preparation of a medicament for lowering blood pressure.