CN113209153B - Eucommia ulmoides composition, preparation method and application thereof - Google Patents
Eucommia ulmoides composition, preparation method and application thereof Download PDFInfo
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- CN113209153B CN113209153B CN202110487882.9A CN202110487882A CN113209153B CN 113209153 B CN113209153 B CN 113209153B CN 202110487882 A CN202110487882 A CN 202110487882A CN 113209153 B CN113209153 B CN 113209153B
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/46—Eucommiaceae (Eucommia family), e.g. hardy rubber tree
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
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- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Diabetes (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the field of cardiovascular treatment, and particularly relates to an eucommia ulmoides composition, a preparation method and application thereof. The composition comprises the following raw materials in parts by weight: 5-15 parts of eucommia male flowers, 5-10 parts of eucommia female flowers, 5-10 parts of eucommia bark and 1-5 parts of eucommia seed oil; the preparation method comprises the steps of enzymolysis, fractional extraction, cyclodextrin inclusion and the like. The preparation method is simple and efficient, the effective components are completely extracted, and the impurity amount is small. The eucommia bark composition prepared by the invention can obviously treat hypertension, promote lipid metabolism of organisms and obviously improve microcirculation of the body surface and internal organs of hypertensive rats.
Description
Technical Field
The invention belongs to the field of cardiovascular treatment, and particularly relates to an eucommia ulmoides composition, a preparation method and application thereof.
Background
Hypertension, also known as elevated blood pressure, is a disease that occurs when blood vessels are continuously subjected to higher pressures. Each contraction of the heart pumps blood into the blood vessels and transports the blood to the whole body through the blood vessels, and the pressure generated when the heart pumps the blood to push the blood against the walls (arteries) of the blood vessels is the blood pressure. The higher the blood pressure, the greater the force with which the heart pumps blood. The blood pressure value (systolic pressure) is about 120 mmhg for a normal adult at systole and about 80 mmhg for a normal adult at diastole. When the systolic pressure is continuously greater than or equal to 140 mm Hg and the diastolic pressure is continuously greater than or equal to 90 mm Hg, the blood pressure is regarded as rising, namely the high blood pressure.
Most hypertensive patients have no obvious symptoms, and thus hypertension is also referred to as "silent killers". The main reason is that hypertension does not directly cause serious physical discomfort, and mainly causes threat to human health through complications such as stroke, myocardial infarction, renal failure, etc., and the higher the blood pressure is, the greater the risk that blood vessels of main organs such as heart, brain, kidney, etc. are damaged, and death can be caused in serious cases.
At present, the medicines for treating hypertension mainly comprise diuretics, beta receptor blockers, calcium antagonists, ACEI, ARB, alpha-receptor blockers and the like, and the medicines have unicity for regulating the hypertension, only perform through individual targets, only temporarily relieve discomfort caused by the rise of the blood pressure, need to take medicines for a long time, cannot radically treat the hypertension, have certain drug resistance, and cause the population of hypertension patients to still have a tendency of continuous expansion. Therefore, a medicine which can integrally regulate the blood circulation system of the organism at multiple targets and achieve the effect of reducing blood pressure is urgently needed to be found.
The traditional Chinese medicine considers that: the spleen and stomach are the acquired root, the source of qi and blood transformation, qi is the commander of blood, blood is the mother of qi, and qi and blood circulation needs the promotion of qi and the nourishing of blood. The traditional Chinese medicine can change abnormal metabolism and the like while reducing blood pressure through multi-target regulation, has unique curative effect advantage and has great potential for preventing and treating hypertension. Modern pharmacological research and clinical research show that many traditional Chinese medicines and Chinese patent medicines such as wild chrysanthemum flower and bezoar antihypertensive pills have obvious antihypertensive effects, but the actual clinical application is still few, the market occupation is small, and the main reason is probably that the advantages and potential of the traditional Chinese medicines for treating hypertension are not fully exerted.
Eucommia ulmoides (Eucommia ulmoides Oliv.) as a larch tree belonging to genus Pinus of family Pinaceae; the parthenocarpy of the flower, the male and female heteroplant, and the leaf are opened simultaneously, or the leaf is opened firstly, and the flower grows in the axilla of the basal bract of the annual branch, and has a flower stalk and no perianth; the male flower has 6-10 stamens, the female flower has a naked and extended ovary, the ovary is 1 chamber, the top end has 2 fork-shaped flower columns, and 1 seed is arranged in the flower columns; the flowering phase is 4-5 months; the fruit period is 9 months.
The eucommia ulmoides has the chemical components of flavonoids, lignans, iridoids, phenolic acids, terpenoids, steroids, polysaccharides and the like, has pharmacological effects of reducing blood pressure, regulating blood fat, reducing blood sugar, resisting inflammation, protecting liver, resisting tumors and the like, contains active components of flavonoids and the like, is rich in various unsaturated fatty acids, mainly comprises active components of linoleic acid, oleic acid, linolenic acid, palmitic acid, stearic acid and the like, and has multiple effects of enhancing memory, easing pain, resisting fatigue, resisting aging, resisting tumors, regulating immune functions and the like. Eucommia bark is a specific medicinal material and woody oil tree species in China, belongs to the second-level precious protective tree species in China, and therefore plant resources need to be utilized more fully.
The Chinese patent CN103356731B discloses a novel Xuesaitong tablet, the effective components of which comprise 1 to 10 parts by weight of eucommia bark extract and 1 to 30 parts by weight of panax notoginseng saponins. The composition also comprises 500 parts of pharmaceutically acceptable auxiliary agents, wherein the auxiliary agents comprise one or more of a disintegrating agent, a stabilizing agent, an excipient, a lubricant and a binder. The invention has good effect in treating hypertension, dizziness, brain stagnation, apoplexy hemiplegia, bone and muscle atrophy, heart stagnation, thoracic obstruction, cardialgia, cerebrovascular disease sequelae, coronary heart disease, angina pectoris and other diseases. The composition adopts Panax notoginsenosides and eucommia ulmoides extract to treat cardiovascular diseases, has low utilization rate of eucommia ulmoides, and has improved effects of treating hypertension and hyperlipemia and improving microcirculation.
Chinese patent CN103768129B discloses a pharmaceutical composition for preventing or treating hypertension, which contains eucommia bark and mistletoe. The pharmaceutical composition has the effects of lowering and stabilizing blood pressure for spontaneous hypertensive rats, but has no obvious effect on improving microcirculation of organisms.
Therefore, the intensive and effective utilization and development of the precious tree species eucommia ulmoides is needed, and a traditional Chinese medicine composition which is reasonable in compatibility and can improve the microcirculation of the organism on the whole to treat cardiovascular diseases is researched.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides the eucommia ulmoides composition for treating hypertension, and the composition can be used for simultaneously and efficiently treating hypertension and hyperlipidemia and improving microcirculation; the preparation method is simple and efficient, the effective components are completely extracted, and the impurity amount is small.
The purpose of the invention is realized by the following technical scheme:
the eucommia ulmoides composition for treating hypertension and hyperlipidemia comprises the following raw materials: eucommia male flower, eucommia female flower, eucommia bark and eucommia seed oil.
Preferably, the raw materials of the composition comprise the following components in parts by weight: 5-15 parts of eucommia male flowers, 5-10 parts of eucommia female flowers, 5-10 parts of eucommia bark and 1-5 parts of eucommia seed oil.
Preferably, the raw materials of the composition comprise the following components in parts by weight: 5-10 parts of eucommia, 5-8 parts of eucommia female flowers, 5-8 parts of eucommia bark and 3-5 parts of eucommia seed oil.
Another object of the present invention is a process for the preparation of the above composition comprising the steps of:
(1) pulverizing cortex Eucommiae, male flower of cortex Eucommiae and female flower of cortex Eucommiae respectively, and sieving;
(2) adding water into cortex Eucommiae, extracting by steam distillation to obtain volatile oil, filtrate 1 and residue 1, adding acetone-containing ethanol water solution into residue 1, and extracting to obtain filtrate 2 and residue 2;
(3) mixing the eucommia male flower, the eucommia female flower and the filter residue 2, adding water, adding cellulase and pectinase for enzymolysis, and filtering to obtain filter residue and enzymolysis liquid;
(4) mixing filtrate 1, filtrate 2 and the enzymolysis solution, adding pectinase and bromelain, performing enzymolysis, inactivating enzyme at 95-100 deg.C, concentrating, and drying to obtain dry extract powder;
(5) mixing the volatile oil and the eucommia seed oil, and performing inclusion by adopting beta-cyclodextrin to obtain an inclusion compound;
(6) mixing the dry extract powder and the clathrate uniformly.
Preferably, the mesh number of the crushed and sieved in the step (1) is 10-24 meshes, acetone is also added into the ethanol solution in the step (2), and the mass ratio of the water to the eucommia ulmoides bark in the step (2) is 6-10:1, the extraction time is 2-4 h.
Preferably, the mass ratio of the ethanol to the acetone to the water is 30-50:10-20: 30-60; the leaching temperature is 40-50 ℃, and the leaching time is 2-3 h;
preferably, the mass ratio of the acetone-containing ethanol solution to the filter residue 1 is 5-8: 1.
preferably, the ratio of the mass of the added water to the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2 in the step (3) is 6-10: 1.
Preferably, the total mass of the cellulase and the pectinase in the step (3) is 0.2-0.5% of the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2; the mass ratio of the cellulase to the pectinase is 1: 2-5;
preferably, the ratio of the mass of the added water to the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2 in the step (3) is 6-10: 1.
Preferably, the enzymolysis temperature in the step (3) is 40-50 ℃, and the enzymolysis time is 1.5-3 h; the pH value of the enzymolysis is 4.0-5.0.
Preferably, in the step (4), the total mass of the pectinase and the bromelain is 0.5-1% of the total mass of the filtrate 1, the filtrate 2 and the enzymolysis liquid, the mass ratio of the pectinase to the bromelain is 1:2-3, the enzymolysis temperature is 35-45 ℃, and the enzymolysis time is 1-2 hours; the pH value of the enzymolysis is 5.0-6.0;
preferably, the mass ratio of the mixture of the volatile oil and the eucommia seed oil in the step (5) to the beta-cyclodextrin is 1: 4-6, the inclusion time is 1-2h, and the inclusion temperature is 45-55 ℃.
The invention further aims to provide the application of the composition in preparing products for resisting hypertension and hyperlipidemia or improving microcirculation of organisms.
The invention has the advantages of
(1) The eucommia ulmoides male flower, the eucommia ulmoides female flower, the eucommia ulmoides bark and the eucommia ulmoides seed oil are compatible, scientific proportion is adopted, the effect of obvious curative effect on hypertension and hyperlipidemia is achieved, compared with chemical medicines, the eucommia ulmoides male flower and eucommia ulmoides female flower medicinal oil has no toxic or side effect, the variety of effective components is multiple, the blood system can be integrally adjusted through multiple targets, and the drug resistance phenomenon cannot occur.
(2) The preparation method of the composition is further researched, active ingredients can be fully extracted by adopting a specific extraction solvent, a specific temperature and a specific enzyme for extraction, and the precious plants with long growth cycles with eucommia ulmoides can be maximally utilized.
(3) The invention adopts the pectinase and the bromelain with specific proportion, not only can remove micromolecule peptide with efficacy effect in a macromolecular protein decomposition tank influencing the solubility of the product, but also can remove tannin, pectin and the like influencing the color, the solubility and the taste, and can furthest retain eucommia polysaccharide with efficacy effect.
The application also carries out a great deal of research on the inclusion process, finds that the proportion of the beta-cyclodextrin to the volatile oil is important, and then the inclusion temperature and the inclusion time are determined, when the proportion of the beta-cyclodextrin to the volatile oil is less than 4: the inclusion rate is low at 1, and the exertion of the drug effect is directly influenced.
Drawings
FIG. 1-1 is a blood perfusion laser Doppler body surface skin line scan of the right palm of rats before drug administration in group of example 1;
FIG. 1-2 is a blood perfusion laser Doppler body surface skin line scan of the right palm of rats after drug administration in the group of example 1;
FIG. 2-1 is a laser Doppler line scan of small intestine blood perfusion in rats before administration in group 3 of example;
FIG. 2-2 is a laser Doppler line scan of small intestine blood perfusion in rats after administration in group 3 of example;
FIG. 3-1 is a laser Doppler scan of spleen, pancreas and kidney microcirculation blood perfusion in rats of the group of example 3 before administration;
FIG. 3-2 is a laser Doppler scan of spleen, pancreas and kidney microcirculation blood perfusion in rats after the administration of the group of example 3;
FIG. 4-1 is a laser Doppler line scan of rat testicular microcirculation blood perfusion after administration in the group of example 3;
FIG. 4-2 is a laser Doppler line scan of rat testicular microcirculation blood perfusion after administration in the group of example 3;
FIG. 5 shows the blood flow rate of small intestine, spleen, pancreas, kidney and testis capillaries of rats in example 3 and comparative example 1; wherein the experimental group is the group of example 3 and the control group is the group of comparative example 1.
Detailed Description
The technical solution of the present invention is further illustrated by the following examples.
Examples below eucommia ulmoides female flowers mature female flowers in which the eucommia ulmoides female flowers are completely opened were harvested.
Example 1
The eucommia ulmoides composition for treating hypertension and hyperlipidemia comprises the raw materials of 5 parts of eucommia male flowers, 5 parts of eucommia female flowers, 5 parts of eucommia bark and 1 part of eucommia seed oil.
The preparation method of the composition comprises the following steps:
(1) respectively pulverizing eucommia male flower, eucommia female flower and eucommia bark, and sieving with 10 mesh sieve;
(2) adding 6 times of water into cortex Eucommiae, extracting for 2h by steam distillation to obtain volatile oil, filtrate 1 and residue 1, adding 8 times of ethanol water solution containing acetone into residue 1, and extracting at 40 deg.C for 2h to obtain filtrate 2 and residue 2; the ethanol: acetone: the ratio of water to water is 30:10: 60;
(3) mixing male flowers of eucommia ulmoides, female flowers of eucommia ulmoides and filter residues 2, adding 6 times of water, performing enzymolysis for 3 hours by using cellulase and pectinase according to the mass ratio of 1:2, adjusting the pH to 4.0, and filtering at the enzymolysis temperature of 40 ℃ to obtain an enzymolysis liquid; wherein the total mass of the cellulase and the pectinase is 0.2 percent of the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2;
(4) mixing filtrate 1, filtrate 2 and the enzymolysis solution, adding pectinase and bromelain (mass ratio of 1:2), performing enzymolysis for 1h, adjusting pH to 5.0, inactivating enzyme at 35 deg.C and 100 deg.C, concentrating, and drying to obtain dry extract powder; wherein the total mass of the pectinase and the bromelain is 0.5 percent of the total mass of the filtrate 1, the filtrate 2 and the enzymatic hydrolysate;
(5) adding water into beta-cyclodextrin to prepare a beta-cyclodextrin solution with the concentration of 0.08g/mL, mixing the volatile oil and the eucommia seed oil, adding the mixture into the beta-cyclodextrin solution, magnetically stirring for 2 hours at the constant temperature of 45 ℃ for 200r/min, cooling, performing suction filtration, washing precipitates with 1 time of water and ethanol in sequence, and drying to obtain an inclusion compound; wherein the mass ratio of the beta-cyclodextrin to the mixture of the volatile oil and the eucommia seed oil is 6: 1.
(6) Mixing the dry extract powder and the clathrate uniformly.
Example 2
The eucommia ulmoides composition for treating hypertension and hyperlipidemia comprises the raw materials of 15 parts of eucommia male flowers, 10 parts of eucommia female flowers, 10 parts of eucommia bark and 5 parts of eucommia seed oil.
The preparation method of the composition comprises the following steps:
(1) respectively pulverizing eucommia male flower, eucommia female flower and eucommia bark, and sieving with 10 mesh sieve;
(2) extracting cortex Eucommiae with 10 times of water by steam distillation for 4 hr to obtain volatile oil, filtrate 1 and residue 1, adding 5 times of ethanol water solution containing acetone into residue 1, and extracting at 50 deg.C for 3 hr to obtain filtrate 2 and residue 2; wherein the mass ratio of the ethanol to the acetone to the water is 50:20: 30;
(3) mixing male flowers of eucommia ulmoides, female flowers of eucommia ulmoides and filter residues 2, adding 10 times of water, performing enzymolysis for 1.5 hours by using cellulase and pectinase according to the mass ratio of 1:5, adjusting the pH to 5.0, controlling the enzymolysis temperature to be 50 ℃, and filtering to obtain an enzymolysis liquid; wherein the total mass of the cellulase and the pectinase is 0.5 percent of the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2;
(4) mixing filtrate 1, filtrate 2 and the enzymolysis solution, adding pectinase and bromelain (mass ratio of 1:3), performing enzymolysis for 2h, adjusting pH to 6.0, inactivating enzyme at 45 deg.C and 95 deg.C, concentrating, and drying to obtain dry extract powder; wherein the total mass of the pectinase and the bromelain is 1 percent of the total mass of the filtrate 1, the filtrate 2 and the enzymatic hydrolysate;
(5) adding water into beta-cyclodextrin to prepare a beta-cyclodextrin solution with the concentration of 0.08g/mL, mixing the volatile oil and the eucommia seed oil, slowly adding the volatile oil and the eucommia seed oil into the beta-cyclodextrin solution, magnetically stirring for 1h at the constant temperature of 55 ℃ for 200r/min, cooling, carrying out suction filtration, washing precipitates with 1 time of water and ethanol in sequence, and drying to obtain an inclusion compound; wherein the mass ratio of the beta-cyclodextrin to the mixture of the volatile oil and the eucommia seed oil is 4: 1.
(6) Mixing the dry extract powder and the clathrate uniformly.
Example 3
The eucommia ulmoides composition for treating hypertension and hyperlipidemia comprises the raw materials of 10 parts of eucommia male flowers, 8 parts of eucommia female flowers, 8 parts of eucommia bark and 3 parts of eucommia seed oil.
The preparation method of the composition comprises the following steps:
(1) respectively pulverizing eucommia male flower, eucommia female flower and eucommia bark, and sieving with 24 mesh sieve;
(2) adding 8 times of water into cortex Eucommiae, extracting for 3h by steam distillation to obtain volatile oil, filtrate 1 and residue 1, adding 6 times of ethanol water solution containing acetone into residue 1, and leaching at 45 deg.C for 2.5h to obtain filtrate 2 and residue 2; wherein the mass ratio of the ethanol to the acetone to the water is 40:15: 45;
(3) mixing male flowers of eucommia ulmoides, female flowers of eucommia ulmoides and filter residues 2, adding water, performing enzymolysis for 2 hours by using cellulase and pectinase according to the mass ratio of 1:3, adjusting the pH value to 4.0, and filtering at the enzymolysis temperature of 45 ℃ to obtain an enzymolysis liquid; wherein the total mass of the cellulase and the pectinase is 0.3 percent of the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2;
(4) mixing filtrate 1, filtrate 2 and the enzymolysis solution, adding pectinase and bromelain (mass ratio of 1:2.5), performing enzymolysis for 1.5h, adjusting pH to 5.5, inactivating enzyme at 45 deg.C and 100 deg.C, concentrating, and drying to obtain dry extract powder; wherein the total mass of the pectinase and the bromelain is 0.8 percent of the total mass of the filtrate 1, the filtrate 2 and the enzymatic hydrolysate;
(5) adding water into beta-cyclodextrin to obtain a beta-cyclodextrin solution with the concentration of 0.08g/mL, mixing the volatile oil and the eucommia seed oil, slowly adding the volatile oil and the eucommia seed oil into the beta-cyclodextrin solution, magnetically stirring for 1.5h at the constant temperature of 50 ℃ and at the speed of 200r/min, cooling, carrying out suction filtration, washing precipitates with 1 time of water and ethanol in sequence, and drying to obtain an inclusion compound; wherein the mass ratio of the beta-cyclodextrin to the mixture of the volatile oil and the eucommia seed oil is 5: 1.
(6) Mixing the dry extract powder and the clathrate uniformly.
Comparative example 1
Compared with example 3, the difference lies in the weight parts of the components of the composition are different;
the eucommia bark composition for treating hypertension and hyperlipidemia in the comparative example comprises the raw materials of 16 parts of eucommia male flowers, 1 part of eucommia female flowers, 11 parts of eucommia bark and 1 part of eucommia seed oil. The rest of the process was identical to example 3.
Comparative example 2
Compared with comparative example 3, the difference is that the weight parts of the components of the composition are different;
the eucommia ulmoides composition for treating hypertension and hyperlipidemia comprises 3 parts of eucommia male flowers, 12 parts of eucommia female flowers, 4 parts of eucommia ulmoides bark and 10 parts of eucommia seed oil. The rest of the process was identical to example 3.
Comparative example 3
The difference from example 3 is that the volume ratio of ethanol, acetone and water in the ethanol solution containing acetone added in step (2) of the preparation method is 15:40:45, and the rest is the same as example 3.
Comparative example 4
The difference compared with example 3 is that papain is used in place of bromelain in step (4) of the preparation method, and the rest is identical with example 3.
Comparative example 5
Compared with the embodiment 3, the difference is that in the step (5) of the preparation method, the mass ratio of the mixture of the volatile oil and the eucommia seed oil to the beta-cyclodextrin is 1:3, the rest of the process was identical to example 3.
Effect example 1 Effect of eucommia ulmoides composition of the present invention on the hypotensive Effect of SHR rats
1.1 purpose: the composition of the invention is used for detecting the effects of reducing blood pressure and blood fat of SHR rats and the effects of the composition on skin (multiple parts) and internal organs (liver leaves, spleen cortex, kidney cortex, small intestine, testis and pancreas microcirculation), and dynamic quantitative analysis of later data and images is carried out, so as to discuss the action path and effective mechanism for regulating and controlling organ microcirculation in the blood pressure reducing and blood vessel elasticity restoring effect of the composition.
1.2 medicine: eucommia ulmoides compositions prepared in examples 1-3 groups and comparative examples 1-5 groups;
1.3 animal grouping and administration
90 spontaneous hypertensive male rats (SHR) with the age of 7-8 weeks are purchased from Beijing Wintonlihua laboratory animal technology GmbH, and the weight of the SHR is 200 + -20 g, and the SHR is fed by standard feed and tap water at the constant temperature of 25 ℃ and the constant humidity of 55 + -5% for one week in an animal laboratory. Spontaneously hypertensive male rats were randomly divided into 9 groups of 10 rats each, including a model group, example 1 group to example 3 group, and comparative 1 group to comparative 5 group;
1.4 test method of hypotensive Effect of the composition of the present invention on SHR rats
Except for the model group, the other groups were continuously administered by gavage for 3 weeks once a day, the dose/kg was equivalent to 15g of crude drug, the blood pressure of the tail artery of the rat was measured before the start of administration and 1h after the last administration (blood pressure was measured for a plurality of times and averaged), and blood was taken to measure the levels of total triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein in serum. Wherein the crude drug amount is the total mass of the raw medicinal materials used for extracting the eucommia bark composition.
The blood pressure monitoring uses a noninvasive blood pressure meter softron BP 2010A; the system comprises a Moor VMS two-channel laser Doppler blood flow (LDF) detection system (dot scanning) and a Moor LDI laser Doppler blood flow imaging system (line scanning).
1.5 results and analysis
(1) The effect of the eucommia ulmoides composition on the mean arterial pressure of the tail artery of the SHR rat is shown in Table 1.
TABLE 1 mean arterial pressure changes in the groups of rats
| Test group | Number of rats (only) | Before administration (mmHg) | After administration (mmHg) |
| Model control group | 10 | 150.9±5.1 | 158.2±4.3a |
| Example 1 | 10 | 149.5±3.6 | 118.2±6.0b |
| Example 2 | 10 | 151.3±4.7 | 119.6±5.2b |
| Example 3 | 10 | 150.1±7.8 | 117.9±3.3b |
| Comparative example 1 | 10 | 151.0±6.0 | 126.5±2.8c |
| Comparative example 2 | 10 | 149.3±3.9 | 129.3±6.2c |
| Comparative example 3 | 10 | 148.6±5.7 | 133.7±2.1c |
| Comparative example 4 | 10 | 150.1±2.4 | 124.8±3.6c |
| Comparative example 5 | 10 | 149.2±7.2 | 137.4±3.9c |
Note: different letters in the same column indicate statistical differences between the corresponding groups, P < 0.05.
(2) The effect of the eucommia ulmoides composition on the metabolism of the blood lipid of SHR rats is shown in Table 2.
TABLE 2 Effect of eucommia ulmoides composition on the metabolism of blood lipids in SHR rats
Note: different letters in the same column indicate statistical differences between the corresponding groups, P < 0.05.
(3) The influence of the eucommia ulmoides composition on the microcirculation of the skin on the body surface of a rat
The study on the microcirculation of the skin of the body surface of SHR rats after the last administration shows that:
1) the blood perfusion PU value of the rats in the groups of examples 1-3 is obviously increased (ear, palm and sole) through laser Doppler body surface skin line scan measurement, and the results before and after administration of the group of example 1 are shown in figures 1-1 and 1-2.
2) The laser Doppler skin spot scanning shows that the blood flow speed of the groups of examples 1-3 is obviously increased, and the concentration of flowing blood cells is reduced differently;
3) wavelet analysis of laser Doppler skin spot scanning results shows that the microcirculation change with the frequency of endothelium origin is the most obvious, and the drug intervention of the groups of examples 1-3 has a certain effect on the autonomy of the microvasculature.
(4) Influence of the eucommia ulmoides composition on microcirculation of viscera of rats
The composition of the example 3 group of SHR rats was subjected to a visceral microcirculation study for the dry prognosis, and as a result, it was found that:
1) after administration, the blood perfusion PU values of small intestine, pancreas, spleen, kidney and testis of rats are remarkably increased compared with the blood perfusion PU values before administration through laser Doppler line scan, and the results of the group of example 3 are shown in figures 2-1, 2-2, 3-1, 3-2, 4-1 and 4-2.
2) The blood flow of the small intestine, pancreas, spleen, kidney and testis capillaries of the rats of the groups of examples 1-3 is obviously increased compared with the blood flow of the capillaries before administration by laser Doppler dot scan measurement. The blood flow rate is also obviously increased, and the blood cell concentration in the microvasculature is obviously reduced, which indicates that the medicine can improve the microcirculation of internal organs after intervention, and the blood flow of stasis becomes smooth (taking spleen, kidney and testis as examples).
The results of blood flow of small intestine, pancreas, spleen, kidney and testis capillaries of rats of example 3 and comparative example 1 (control group) are shown in FIG. 5.
3) Laser Doppler visceral spot scan wavelet analysis shows that the microcirculation change with the frequency of endothelium source is the most obvious, and the drug intervention has certain effect on the autonomy of visceral (small intestine, spleen, pancreas, kidney and testis) microvasculature.
And (4) analyzing results: the eucommia bark composition prepared by the invention has obvious treatment effect on hypertension, and simultaneously can also obviously improve the lipid metabolism of organisms; the eucommia ulmoides composition can improve the microcirculation of hypertensive rats under the condition of effectively regulating and controlling the blood pressure of the rats, and is characterized in that the flow velocity of the capillaries on the skin of ears, palms and soles is obviously increased compared with that before administration, the concentration of the blood cells of the capillaries is reduced, and the blood flow of microcirculation stasis is relieved. The micro-vascular flow rates on the internal organs, small intestine, spleen, pancreas, kidney and testis were also significantly increased, the micro-vascular blood cell concentration was decreased, and the blood flow of the microcirculation stasis was relieved in examples 1 to 3 as compared with those before self-administration and after administration in the comparative example group.
The above detailed description is specific to one possible embodiment of the present invention, and the embodiment is not intended to limit the scope of the present invention, and all equivalent implementations or modifications without departing from the scope of the present invention should be included in the technical scope of the present invention.
Claims (12)
1. The eucommia ulmoides composition for treating hypertension and improving microcirculation of organisms comprises the following raw materials in parts by weight: 5-15 parts of eucommia male flowers, 5-10 parts of eucommia female flowers, 5-10 parts of eucommia bark and 1-5 parts of eucommia seed oil;
the preparation method of the composition comprises the following steps:
(1) pulverizing cortex Eucommiae, male flower of cortex Eucommiae and female flower of cortex Eucommiae respectively, and sieving;
(2) adding water into cortex Eucommiae, extracting by steam distillation to obtain volatile oil, filtrate 1 and residue 1, adding ethanol water solution containing acetone into residue 1, and extracting to obtain filtrate 2 and residue 2;
(3) mixing the eucommia male flower, the eucommia female flower and the filter residue 2, adding water, adding cellulase and pectinase for enzymolysis, and filtering to obtain filter residue and enzymolysis liquid;
(4) mixing filtrate 1, filtrate 2 and the enzymolysis solution, adding pectinase and bromelain, performing enzymolysis, inactivating enzyme at 95-100 deg.C, concentrating, and drying to obtain dry extract powder;
(5) mixing the volatile oil and the eucommia seed oil, and performing inclusion by adopting beta-cyclodextrin to obtain an inclusion compound;
(6) mixing the dry extract powder and the clathrate uniformly.
2. The composition as claimed in claim 1, wherein the raw materials of the composition comprise the following components in parts by weight: 5-10 parts of eucommia male flowers, 5-8 parts of eucommia female flowers, 5-8 parts of eucommia bark and 3-5 parts of eucommia seed oil.
3. A process for the preparation of a composition according to any one of claims 1 to 2, characterized in that it comprises the following steps:
(1) pulverizing cortex Eucommiae, male flower of cortex Eucommiae and female flower of cortex Eucommiae respectively, and sieving;
(2) adding water into cortex Eucommiae, extracting by steam distillation to obtain volatile oil, filtrate 1 and residue 1, adding ethanol water solution containing acetone into residue 1, and extracting to obtain filtrate 2 and residue 2;
(3) mixing the eucommia male flower, the eucommia female flower and the filter residue 2, adding water, adding cellulase and pectinase for enzymolysis, and filtering to obtain filter residue and enzymolysis liquid;
(4) mixing filtrate 1, filtrate 2 and the enzymolysis solution, adding pectinase and bromelain, performing enzymolysis, inactivating enzyme at 95-100 deg.C, concentrating, and drying to obtain dry extract powder;
(5) mixing the volatile oil and the eucommia seed oil, and performing inclusion by adopting beta-cyclodextrin to obtain an inclusion compound;
(6) mixing the dry extract powder and the clathrate uniformly.
4. The method according to claim 3, wherein the mesh number of the pulverizing and sieving in the step (1) is 10 to 24 meshes; in the step (2), the mass ratio of the water to the eucommia ulmoides bark is 6-10:1, the extraction time of the steam distillation method is 2-4 h.
5. The preparation method according to claim 3, wherein the mass ratio of ethanol, acetone and water in the acetone-containing ethanol aqueous solution in the step (2) is 30-50:10-20: 30-60; the leaching temperature is 40-50 ℃, and the leaching time is 2-3 h.
6. The preparation method according to claim 3, wherein the mass ratio of the ethanol aqueous solution containing acetone to the filter residue 1 in the step (2) is 5-8: 1.
7. the preparation method according to claim 3, wherein the total mass of the cellulase and the pectinase in the step (3) is 0.2-0.5% of the total mass of the eucommia male flower, the eucommia female flower and the filter residue 2; the mass ratio of the cellulase to the pectinase is 1: 2-5.
8. The preparation method according to claim 3, wherein the ratio of the mass of the added water to the total mass of the eucommia male flower, the eucommia female flower and the residue 2 in step (3) is 6-10: 1.
9. The preparation method according to claim 3, wherein the temperature of the enzymolysis in the step (3) is 40-50 ℃, and the time of the enzymolysis is 1.5-3 h; the pH value of the enzymolysis is 4.0-5.0.
10. The preparation method according to claim 3, wherein the total mass of the pectinase and the bromelain in the step (4) is 0.5-1% of the total mass of the filtrate 1, the filtrate 2 and the enzymatic hydrolysate, the mass ratio of the pectinase to the bromelain is 1:2-3, the enzymolysis temperature is 35-45 ℃, and the enzymolysis time is 1-2 hours; the pH value of the enzymolysis is 5.0-6.0.
11. The preparation method according to claim 3, wherein the mass ratio of the mixture of the volatile oil and the eucommia seed oil to the beta-cyclodextrin in the step (5) is 1: 4-6, the inclusion time is 1-2h, and the inclusion temperature is 45-55 ℃.
12. The use of the composition according to any one of claims 1-2 for the preparation of a medicament for the treatment of hypertension, hyperlipidemia or improving microcirculation of the body or a health food for the adjuvant treatment of hypertension and hyperlipidemia.
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| CN114224934B (en) * | 2021-12-29 | 2024-01-02 | 国际遗传工程和生物技术中心泰州区域研究中心 | Eucommia ulmoides extract for improving microcirculation |
| CN114403434A (en) * | 2022-01-12 | 2022-04-29 | 山东贝隆杜仲生物工程有限公司 | Composition with blood pressure lowering effect and prepared from eucommia ulmoides as raw material and preparation method |
| CN114731857B (en) * | 2022-02-28 | 2023-10-27 | 江西普正制药股份有限公司 | Cutting propagation method of eucommia ulmoides |
| CN115428952A (en) * | 2022-09-27 | 2022-12-06 | 河南磐康健康管理股份有限公司 | Composition for preventing and improving diseases related to microcirculation disturbance, preparation method and application thereof |
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| CN102336795A (en) * | 2011-07-20 | 2012-02-01 | 河南科技大学 | Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof |
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