CN117244027A - A pharmaceutical composition for treating cardiovascular diseases, and its preparation method - Google Patents

A pharmaceutical composition for treating cardiovascular diseases, and its preparation method Download PDF

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CN117244027A
CN117244027A CN202311156768.3A CN202311156768A CN117244027A CN 117244027 A CN117244027 A CN 117244027A CN 202311156768 A CN202311156768 A CN 202311156768A CN 117244027 A CN117244027 A CN 117244027A
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parts
colon
pharmaceutical composition
treating cardiovascular
solution
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CN117244027B (en
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邵月霞
杜康丽
卢东辉
孟伟
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Tianjin Huanhu Hospital (tianjin Neurosurgery Department Institute Tianjin Brain Central Hospital)
Shandong Taishan Hospital
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Tianjin Huanhu Hospital (tianjin Neurosurgery Department Institute Tianjin Brain Central Hospital)
Shandong Taishan Hospital
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Abstract

The invention discloses a pharmaceutical composition for treating cardiovascular diseases and a preparation method thereof, and relates to the technical field of medicines; the pharmaceutical composition for treating cardiovascular diseases comprises colon targeted hydrogel, campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, peucedanum root and lecithin; the colon targeting hydrogel consists of konjak fine powder, chitosan and lycopene; the co-coagulation gel of the carboxymethyl konjak glucomannan and the chitosan has high specific surface area and high porosity, and enhances the adsorption performance on cholesterol and triglyceride; the carboxymethyl konjaku glucomannan has the colon targeting function, and the hydrogel adheres the traditional Chinese medicine extract on the surface of the colon, so that the traditional Chinese medicine extract stays for a long time, the concentration and the absorption of the traditional Chinese medicine extract are improved, and the bioavailability is further improved; lycopene increases oxidation resistance of colon-targeted hydrogel, inhibits platelet aggregation, and reduces lipid peroxidation.

Description

A pharmaceutical composition for treating cardiovascular diseases, and its preparation method
Technical Field
The invention belongs to the technical field of medicines, and in particular relates to a pharmaceutical composition for treating cardiovascular diseases and a preparation method thereof.
Background
Cardiovascular diseases generally refer to ischemic or hemorrhagic diseases of heart and whole body tissues caused by hyperlipidemia, blood viscosity, atherosclerosis and the like, and are mainly characterized by pathological changes of arterial blood vessels, so that the blood supply and tissue oxygenation functions of the heart are damaged; hemorrhagic cardiovascular diseases generally have a history of hypertension and poor blood pressure control, and often have severe increases in blood pressure and ruptured blood vessels during emotional agitation, while ischemic cardiovascular diseases are mainly caused by vessel blockage or embolism.
Dyslipidemia is one of the most important risk factors of ischemic cardiovascular diseases, low-density lipoprotein cholesterol can be deposited in arterial walls to form plaques, the plaques comprise stable plaques and unstable plaques, the stable plaques are small in skin thickness and stuffing and are not easy to break, so that blood vessels are narrowed or slowly blocked, and coronary heart disease is caused; the unstable plaque is 'thin and large in skin and stuffing', is easy to break, and lipid substances in the unstable plaque are exposed in blood to cause a large amount of platelets to gather and form thrombus, so that risks of acute myocardial infarction, sudden death, cerebral embolism and the like occur.
The clinical therapeutic drugs mainly comprise the functions of dilating blood vessels, reducing blood fat, resisting platelet aggregation, resisting thrombus, protecting vascular endothelium, stabilizing plaques and the like, for example, statins inhibit the synthesis of cholesterol in vivo, betamine and nicotinic acid reduce triglyceride and low-density protein cholesterol, aspirin inhibit cyclooxygenase of platelets, improve vascular abnormalities to a certain extent, and are used for preventing and treating cardiovascular diseases such as coronary heart disease, ischemic cerebral apoplexy and the like.
The prior art mainly has the following problems:
the chemical medicines have single action form and low bioavailability, and have serious adverse reactions of gastrointestinal tracts;
in order to improve the treatment effect, the combined medicines with different action mechanisms can further aggravate adverse reactions such as affecting liver functions, causing muscle injury, causing muscle dissolution and causing other adverse reactions such as new diabetes when achieving the target effect.
Disclosure of Invention
Aiming at the situation, in order to overcome the defects of the prior art, the invention provides a pharmaceutical composition for treating cardiovascular diseases, which comprises the following components in parts by weight: 20-30 parts of colon-targeted hydrogel, 20-25 parts of campsis grandiflora, 20-25 parts of erigeron breviscapus, 20-25 parts of ligusticum chuanxiong, 15-20 parts of rhizoma sparganii, 10-15 parts of fingered citron, 10-15 parts of radix peucedani and 8-12 parts of lecithin.
The colon targeting hydrogel comprises the following components in parts by weight: 5-8 parts of konjak fine powder, 15-20 parts of chitosan and 5-10 parts of lycopene.
The preparation method of the colon-targeted hydrogel specifically comprises the following steps:
(1) Stirring konjak fine powder, adding into water, swelling for 0.5h, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide according to a weight ratio of 6:1, reacting for 1-2h, taking out, cooling, adding an equal weight of acetone precipitate, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking with absolute ethanol overnight, drying at a constant temperature of 45-55 ℃ for 15-30min, and obtaining carboxymethyl konjak glucomannan;
(2) Dissolving chitosan in acetic acid solution with volume fraction of 1%, adding lycopene, stirring, heating in water bath to 50-60deg.C, adding sodium chloride solution with volume fraction of 1% -3% into chitosan acetic acid solution containing lycopene, and dissolving uniformly to obtain chitosan solution;
(3) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water to obtain carboxymethyl konjak glucomannan solution, heating in a water bath to 50-60 ℃, adding sodium chloride solution with the volume fraction of 1-3% into the carboxymethyl konjak glucomannan solution, uniformly dissolving, adding the chitosan solution obtained in the step (2), blending for 30min, and controlling the temperature to 60-70 ℃ to obtain colon-targeted hydrogel;
preferably, in the step (1), the weight ratio of the konjak fine powder to the water is 1 (80-100);
preferably, in the step (1), the volume fraction of chloroacetic acid in the mixed solution of chloroacetic acid and potassium iodide is 1%, and the volume fraction of potassium iodide is 0.2%;
preferably, in the step (2), the weight ratio of chitosan to acetic acid solution is 1 (5-8);
preferably, in the step (2), the weight ratio of the chitosan acetic acid solution containing lycopene to the sodium chloride solution is (15-20): 1;
preferably, in the step (3), the weight ratio of the carboxymethyl konjac glucomannan to the water is 1 (10-15);
preferably, in the step (3), the weight ratio of the carboxymethyl konjac glucomannan solution to the sodium chloride solution is (20-25): 1.
The preparation method of the pharmaceutical composition for treating cardiovascular diseases comprises the following steps:
s1, soaking campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum in water in a decocting machine for 2-4 hours, decocting for 1-2 times, extracting for 2-3 hours by micro boiling, mixing decoctions, filtering, concentrating filtrate, vacuum pressure-0.06 MPa, temperature 50-55 ℃, drying at 40-50 ℃ for 20-25 minutes to obtain a traditional Chinese medicine extract;
s2, adding the colon-targeted hydrogel into water, heating and stirring, adding lecithin, continuously stirring, adding the traditional Chinese medicine extract in the step S1, uniformly stirring, drying at 40-50 ℃ for 20-30min, and obtaining the pharmaceutical composition for treating cardiovascular diseases;
preferably, in the step S1, the weight ratio of the total weight of the campsis grandiflora, the erigeron breviscapus, the ligusticum chuanxiong, the rhizoma sparganii, the fingered citron, the citron and the peucedanum root to the water is 1:15;
preferably, in step S2, the weight ratio of colon targeted hydrogel to water is 1 (30-40).
The beneficial effects obtained by the invention are as follows:
according to the invention, the traditional Chinese medicine extract is combined with the colon-targeted hydrogel, so that the traditional Chinese medicine extract which is difficult to absorb is delivered in a colon-targeted manner, the bioavailability is effectively improved, and the adverse reaction of stomach is reduced; the colon-targeted hydrogel has the advantages that carboxyl introduced by carboxymethyl konjaku glucomannan enhances intermolecular hydrogen bonds to increase solubility, salt ions, carboxymethyl konjaku glucomannan and chitosan form interchain salt bonds, the molecular crosslinking effect is enhanced, the mechanical property of the co-coagulation gel is improved, the stability in the gastrointestinal tract is improved, the gastrointestinal tract is protected, and adverse reactions are reduced; the co-coagulation gel of the carboxymethyl konjak glucomannan and the chitosan has high specific surface area and high porosity, increases the adsorption quantity of single gel, strengthens the adsorption performance on harmful substances such as cholesterol, triglyceride, cholic acid and the like, inhibits the fat decomposed by the substances such as the cholesterol and the like from being absorbed by the small intestine and discharges the cholesterol out of the body; the carboxymethyl konjaku glucomannan has the colon targeting function, and the hydrogel adheres the traditional Chinese medicine extract on the surface of the colon, so that the traditional Chinese medicine extract stays for a long time, the concentration and the absorption of the traditional Chinese medicine extract are improved, and the bioavailability is further improved; lycopene increases oxidation resistance of colon-targeted hydrogel, inhibits platelet aggregation, and reduces lipid peroxidation; the colon-targeted hydrogel has good blood lipid reducing and antithrombotic effects, and has the effects of preventing and treating hypertension and hyperglycemia under the synergistic effect of carboxymethyl konjak glucomannan and chitosan;
the campsis grandiflora (flavonoids) and the erigeron breviscapus (breviscapine) cooperate to achieve the effects of reducing blood viscosity and improving blood circulation; rhizoma Sparganii (triterpenes) can reduce platelet number, and can be used in combination with fructus Citri Sarcodactylis (bergapten, lemon lactone, hesperidin) and fructus Citri (hesperidin) to increase antithrombotic effect; the campsis grandiflora inhibits the human acyl coenzyme and the cholesterol transport enzyme, the rhizoma sparganii has a binding effect on an angiotensin II receptor and a calcium channel blocker receptor, and the multi-drug combination achieves the effects of dilating blood vessels, reducing blood fat and resisting thrombus in various forms; ligusticum wallichii (ligustrazine) has qi-moving function, can enhance the effects of promoting blood circulation and removing blood stasis of campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron and citron, and also can protect the heart together with peucedanum root (coumarin); the lecithin not only increases the wettability and dispersibility of the traditional Chinese medicine extract, but also can reduce fat precipitation in blood vessels, and is beneficial to cardiovascular health; the invention uses colon-targeted hydrogel, campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, peucedanum root and lecithin to prepare a pharmaceutical composition for treating cardiovascular diseases, thereby reducing adverse reactions of gastrointestinal tracts, improving bioavailability and effectively treating ischemic cardiovascular diseases.
Drawings
FIG. 1 is a scanning electron microscope image of a colon targeted hydrogel prepared in example 1 of the present invention;
FIG. 2 is a graph showing the results of triglyceride levels for examples 1-4 and comparative examples 1-3 of the present invention;
FIG. 3 is a graph showing results of cholesterol levels in examples 1 to 4 and comparative examples 1 to 3 according to the present invention;
FIG. 4 is a graph showing the platelet inhibition results of examples 1 to 4 and comparative examples 1 to 3 of the present invention;
FIG. 5 is a graph showing the adverse reaction results of examples 1 to 4 and comparative examples 1 to 3 according to the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention; all other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the present invention. The preferred methods and materials described herein are illustrative only and should not be construed as limiting the scope of the present application.
The experimental methods in the following examples are all conventional methods unless otherwise specified; the test materials used in the examples described below, unless otherwise specified, were purchased from commercial sources.
The sources of reagents used in the examples are as follows:
chitosan CASNo 9012-76-4, brand Innochem, cat# A73336;
chloroacetic acid CASNo 79-11-8, alfa brand, cat# A11482;
potassium iodide CASNo 7681-11-0, brand Innochem, cat# A71995;
acetone CASNo 64-19-7, acros brand, cat# 176800025;
absolute ethyl alcohol CASNo, 64-17-5, brand Innochem, product number G00004;
CASNo acetate 7585-39-9, innochem, cat# A27238;
lycopene CASNo 502-65-8, brand Apino, cat# GC74398;
sodium chloride CASNo 7647-14-5, brand Innochem, cat# A63214;
lecithin CASNo 8002-43-5, innochem brand, cat# A71764.
Example 1
The embodiment provides a pharmaceutical composition for treating cardiovascular diseases, which comprises the following components in parts by weight: 20 parts of colon-targeted hydrogel, 25 parts of campsis grandiflora, 25 parts of erigeron breviscapus, 25 parts of ligusticum chuanxiong, 20 parts of rhizoma sparganii, 15 parts of fingered citron, 15 parts of radix peucedani and 12 parts of lecithin.
The colon targeting hydrogel comprises the following components in parts by weight: 5 parts of konjak fine powder, 20 parts of chitosan and 10 parts of lycopene.
The preparation method of the colon-targeted hydrogel specifically comprises the following steps:
(1) Stirring konjak fine powder, adding into water, swelling for 0.5h at a weight ratio of 1:100, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide at a weight ratio of 6:1, reacting for 2h at a volume fraction of 1% in the mixed solution of chloroacetic acid and potassium iodide, taking out, cooling, adding an equal weight of acetone for precipitation, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking overnight with absolute ethyl alcohol, drying at a constant temperature of 55 ℃ for 15min to obtain carboxymethyl konjak glucomannan;
(2) Dissolving chitosan in acetic acid solution with volume fraction of 1%, adding lycopene in the weight ratio of 1:8, stirring, heating in water bath at 60deg.C, adding sodium chloride solution with volume fraction of 3% into chitosan acetic acid solution containing lycopene in the weight ratio of 20:1, and dissolving uniformly to obtain chitosan solution;
(3) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water, wherein the weight ratio of the carboxymethyl konjak glucomannan to the water is 1:15, obtaining carboxymethyl konjak glucomannan solution, heating in a water bath to 60 ℃, adding a sodium chloride solution with the volume fraction of 3% into the carboxymethyl konjak glucomannan solution, wherein the weight ratio of the carboxymethyl konjak glucomannan solution to the sodium chloride solution is 25:1, dissolving uniformly, adding the chitosan solution obtained in the step (2), blending for 30min, and controlling the temperature to 70 ℃ to obtain the colon-targeted hydrogel.
The embodiment provides a preparation method of a pharmaceutical composition for treating cardiovascular diseases, which specifically comprises the following steps:
s1, placing campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum into a decocting machine to be soaked for 4 hours, wherein the weight ratio of the total weight of campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum to water is 1:15, decocting for 2 times, carrying out micro-boiling extraction for 3 hours, mixing decoctions, filtering, concentrating the filtrate, carrying out vacuum pressure of-0.06 MPa, and drying at the temperature of 55 ℃ for 20 minutes, thereby obtaining a traditional Chinese medicine extract;
s2, adding the colon-targeted hydrogel into water, heating and stirring the colon-targeted hydrogel and the water according to the weight ratio of 1:40, adding lecithin, continuously stirring, adding the traditional Chinese medicine extract in the step S1, uniformly stirring, drying at the drying temperature of 50 ℃ for 20min, and obtaining the pharmaceutical composition for treating cardiovascular diseases.
In this example, a scanning electron microscope is used to observe the microscopic morphology of the prepared colon-targeted hydrogel, and fig. 1 is an SEM image of the colon-targeted hydrogel prepared in example 1, which is 5 times magnified, and the colon-targeted hydrogel prepared in this example is a high-void hydrogel carrier.
Example 2
The embodiment provides a pharmaceutical composition for treating cardiovascular diseases, which comprises the following components in parts by weight: 20 parts of colon-targeted hydrogel, 20 parts of campsis grandiflora, 20 parts of erigeron breviscapus, 20 parts of ligusticum chuanxiong, 15 parts of rhizoma sparganii, 10 parts of fingered citron, 10 parts of radix peucedani and 8 parts of lecithin.
The colon targeting hydrogel comprises the following components in parts by weight: 5 parts of konjak fine powder, 15 parts of chitosan and 5 parts of lycopene.
The preparation method of the colon-targeted hydrogel specifically comprises the following steps:
(1) Stirring konjak fine powder, adding into water, swelling for 0.5h at a weight ratio of 1:80, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide at a weight ratio of 6:1, reacting for 1h at a volume fraction of 1% in the mixed solution of chloroacetic acid and potassium iodide, taking out, cooling, adding an equal weight of acetone for precipitation, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking with absolute ethyl alcohol overnight, drying at a constant temperature of 45 ℃ for 30min to obtain carboxymethyl konjak glucomannan;
(2) Dissolving chitosan in acetic acid solution with volume fraction of 1%, adding lycopene in the weight ratio of 1:5, stirring, heating in water bath to 50deg.C, adding sodium chloride solution with volume fraction of 1% into chitosan acetic acid solution containing lycopene in the weight ratio of 15:1, and dissolving uniformly to obtain chitosan solution;
(3) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water, wherein the weight ratio of the carboxymethyl konjak glucomannan to the water is 1:10, obtaining carboxymethyl konjak glucomannan solution, heating the carboxymethyl konjak glucomannan solution in a water bath to 50 ℃, adding a sodium chloride solution with the volume fraction of 1% into the carboxymethyl konjak glucomannan solution, wherein the weight ratio of the carboxymethyl konjak glucomannan solution to the sodium chloride solution is 20:1, uniformly dissolving, adding the chitosan solution obtained in the step (2), blending for 30min, and controlling the temperature to 60 ℃ to obtain the colon-targeted hydrogel.
The embodiment provides a preparation method of a pharmaceutical composition for treating cardiovascular diseases, which specifically comprises the following steps:
s1, placing campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum into a decocting machine to be soaked for 2 hours, wherein the weight ratio of the total weight of campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum to water is 1:15, decocting for 1 time, carrying out micro-boiling extraction for 2 hours, mixing decoctions, filtering, concentrating the filtrate, carrying out vacuum pressure of-0.06 MPa, and drying at the temperature of 50 ℃, wherein the drying temperature is 40 ℃ and the drying time is 25 minutes, thus obtaining a traditional Chinese medicine extract;
s2, adding the colon-targeted hydrogel into water, heating and stirring the colon-targeted hydrogel and the water according to the weight ratio of 1:30, adding lecithin, continuously stirring, adding the traditional Chinese medicine extract in the step S1, uniformly stirring, drying at 40 ℃ for 30min, and obtaining the pharmaceutical composition for treating cardiovascular diseases.
Example 3
The embodiment provides a pharmaceutical composition for treating cardiovascular diseases, which comprises the following components in parts by weight: 30 parts of colon-targeted hydrogel, 25 parts of campsis grandiflora, 25 parts of erigeron breviscapus, 25 parts of ligusticum chuanxiong, 20 parts of rhizoma sparganii, 15 parts of fingered citron, 15 parts of radix peucedani and 12 parts of lecithin.
The colon targeting hydrogel comprises the following components in parts by weight: 8 parts of konjak fine powder, 20 parts of chitosan and 10 parts of lycopene.
The preparation method of the colon-targeted hydrogel specifically comprises the following steps:
(1) Stirring konjak fine powder, adding into water, swelling for 0.5h at a weight ratio of 1:100, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide at a weight ratio of 6:1, reacting for 2h at a volume fraction of 1% in the mixed solution of chloroacetic acid and potassium iodide, taking out, cooling, adding an equal weight of acetone for precipitation, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking overnight with absolute ethyl alcohol, drying at a constant temperature of 55 ℃ for 30min to obtain carboxymethyl konjak glucomannan;
(2) Dissolving chitosan in acetic acid solution with volume fraction of 1%, adding lycopene in the weight ratio of 1:8, stirring, heating in water bath at 60deg.C, adding sodium chloride solution with volume fraction of 1% into chitosan acetic acid solution containing lycopene in the weight ratio of 15:1, and dissolving uniformly to obtain chitosan solution;
(3) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water, wherein the weight ratio of the carboxymethyl konjak glucomannan to the water is 1:15, obtaining carboxymethyl konjak glucomannan solution, heating in a water bath to 60 ℃, adding a sodium chloride solution with the volume fraction of 1% into the carboxymethyl konjak glucomannan solution, wherein the weight ratio of the carboxymethyl konjak glucomannan solution to the sodium chloride solution is 25:1, dissolving uniformly, adding the chitosan solution obtained in the step (2), blending for 30min, and controlling the temperature to 70 ℃ to obtain the colon-targeted hydrogel.
The embodiment provides a preparation method of a pharmaceutical composition for treating cardiovascular diseases, which specifically comprises the following steps:
s1, placing campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum into a decocting machine to be soaked for 4 hours, wherein the weight ratio of the total weight of campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum to water is 1:15, decocting for 2 times, carrying out micro-boiling extraction for 3 hours, mixing decoctions, filtering, concentrating the filtrate, carrying out vacuum pressure of-0.06 MPa, and drying at the temperature of 55 ℃, wherein the drying temperature is 50 ℃ and the drying time is 25 minutes, thus obtaining a traditional Chinese medicine extract;
s2, adding the colon-targeted hydrogel into water, wherein the weight ratio of the colon-targeted hydrogel to the water is 1:40), heating and stirring, adding lecithin, continuously stirring, adding the traditional Chinese medicine extract in the step S1, uniformly stirring, drying at 50 ℃ for 30min, and obtaining the pharmaceutical composition for treating cardiovascular diseases.
Example 4
The embodiment provides a pharmaceutical composition for treating cardiovascular diseases, which comprises the following components in parts by weight: 30 parts of colon-targeted hydrogel, 20 parts of campsis grandiflora, 20 parts of erigeron breviscapus, 20 parts of ligusticum chuanxiong, 15 parts of rhizoma sparganii, 10 parts of fingered citron, 10 parts of radix peucedani and 8 parts of lecithin.
The colon targeting hydrogel comprises the following components in parts by weight: 8 parts of konjak fine powder, 15 parts of chitosan and 5 parts of lycopene.
The preparation method of the colon-targeted hydrogel specifically comprises the following steps:
(1) Stirring konjak fine powder, adding into water, swelling for 0.5h at a weight ratio of 1:80, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide at a weight ratio of 6:1, reacting for 1h at a volume fraction of 1% in the mixed solution of chloroacetic acid and potassium iodide, taking out, cooling, adding an equal weight of acetone for precipitation, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking with absolute ethyl alcohol overnight, drying at a constant temperature of 45 ℃ for 15min to obtain carboxymethyl konjak glucomannan;
(2) Dissolving chitosan in acetic acid solution with volume fraction of 1%, adding lycopene in the weight ratio of 1:5, stirring, heating in water bath to 50deg.C, adding sodium chloride solution with volume fraction of 3% into chitosan acetic acid solution containing lycopene in the weight ratio of 15:1, and dissolving uniformly to obtain chitosan solution;
(3) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water, wherein the weight ratio of the carboxymethyl konjak glucomannan to the water is 1:10, obtaining carboxymethyl konjak glucomannan solution, heating the carboxymethyl konjak glucomannan solution in a water bath to 50 ℃, adding a sodium chloride solution with the volume fraction of 3% into the carboxymethyl konjak glucomannan solution, wherein the weight ratio of the carboxymethyl konjak glucomannan solution to the sodium chloride solution is 20:1, uniformly dissolving, adding the chitosan solution obtained in the step (2), blending for 30min, and controlling the temperature to 60 ℃ to obtain the colon-targeted hydrogel.
The embodiment provides a preparation method of a pharmaceutical composition for treating cardiovascular diseases, which specifically comprises the following steps:
s1, placing campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum into a decocting machine to be soaked for 2 hours, wherein the weight ratio of the total weight of campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum to water is 1:15, decocting for 1 time, carrying out micro-boiling extraction for 2 hours, mixing decoctions, filtering, concentrating the filtrate, carrying out vacuum pressure of-0.06 MPa, and drying at the temperature of 50 ℃, wherein the drying temperature is 40 ℃ and the drying time is 20 minutes, thus obtaining a traditional Chinese medicine extract;
s2, adding the colon-targeted hydrogel into water, heating and stirring the colon-targeted hydrogel and the water according to the weight ratio of 1:30, adding lecithin, continuously stirring, adding the traditional Chinese medicine extract in the step S1, uniformly stirring, drying at 40 ℃ for 20min, and obtaining the pharmaceutical composition for treating cardiovascular diseases.
Comparative example 1
This comparative example provides a pharmaceutical composition for treating cardiovascular disease, which differs from example 1 in that the pharmaceutical composition for treating cardiovascular disease does not contain a colon targeting hydrogel; the preparation method of the pharmaceutical composition for treating cardiovascular diseases is the same as in example 1.
Comparative example 2
This comparative example provides a pharmaceutical composition for treating cardiovascular disease, which differs from example 1 in that the colon targeted hydrogel does not contain konjak fine powder; the preparation method of the colon targeting hydrogel does not comprise the steps (1) and (3); the preparation method of the pharmaceutical composition for treating cardiovascular diseases is the same as in example 1.
Comparative example 3
This comparative example provides a pharmaceutical composition for treating cardiovascular disease, which differs from example 1 in that the colon targeted hydrogel does not contain chitosan.
The preparation method of the colon-targeted hydrogel specifically comprises the following steps:
(1) Stirring konjak fine powder, adding into water, swelling for 0.5h at a weight ratio of 1:100, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide at a weight ratio of 6:1, reacting for 2h at a volume fraction of 1% in the mixed solution of chloroacetic acid and potassium iodide, taking out, cooling, adding an equal weight of acetone for precipitation, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking overnight with absolute ethyl alcohol, drying at a constant temperature of 55 ℃ for 15min to obtain carboxymethyl konjak glucomannan;
(2) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water, wherein the weight ratio of the carboxymethyl konjak glucomannan to the water is 1:15, adding lycopene, stirring, heating in a water bath to 60 ℃, adding a sodium chloride solution with the volume fraction of 3% into the carboxymethyl konjak glucomannan solution containing lycopene, wherein the weight ratio of the carboxymethyl konjak glucomannan solution containing lycopene to the sodium chloride solution is 25:1, uniformly dissolving, and controlling the temperature to 70 ℃ to obtain the colon-targeted hydrogel.
The preparation method of the pharmaceutical composition for treating cardiovascular diseases is the same as in example 1.
Experimental example 1
Blood lipid content experiment
Test sample: the pharmaceutical compositions for treating cardiovascular diseases prepared in examples 1 to 4 and comparative examples 1 to 3.
The testing method comprises the following steps: 35 male rats, 160-180g in weight, are fed adaptively for 5 days, and are randomly divided into 7 groups by using a random number table after being layered according to the weight, wherein 5 animals are in each group; the high-fat feed comprises the following components: 10% of lard, 2% of cholesterol, 0.2% of propylthiouracil, 0.5% of pig bile salt and 87.3% of basal feed, and the test sample is fed while feeding the high-fat feed, and rats are anesthetized with 25% uratein (0.4 ml/100 g) on 19 consecutive days and 20 th day, collected from abdominal aorta, and serum is centrifugally separated to determine triglyceride TG (mmol/L) and cholesterol CHO (mmol/L).
FIG. 2 is a graph showing the results of triglyceride content in examples 1 to 4 and comparative examples 1 to 3, and FIG. 3 is a graph showing the results of cholesterol content in examples 1 to 4 and comparative examples 1 to 3; as shown in the figure, the triglyceride TG in examples 1-4 is 0.45-0.58mmol/L, the cholesterol CHO is 4.5-5mmol/L, and the triglyceride and cholesterol contents are low; the triglyceride TG of comparative examples 1-3 was 0.72-0.8mmol/L, cholesterol CHO was 7.5-8mmol/L, and the triglyceride and cholesterol contents were high; the pharmaceutical composition for treating cardiovascular diseases of comparative example 1 does not contain colon-targeted hydrogel, the traditional Chinese medicine extract cannot adhere to the colon, the concentration and absorption of the traditional Chinese medicine extract are reduced, and meanwhile, the absorption and discharge of cholesterol and the like by the hydrogel are absent, so that the content of cholesterol and triglyceride in blood fat is higher; the colon targeting hydrogel of the comparative example 2 does not contain konjak fine powder, so that targeting is eliminated, and further, bioavailability is reduced, and the content of cholesterol and triglyceride in blood fat is higher; the colon targeting hydrogel of the comparative example 3 does not contain chitosan, reduces the adsorptivity to cholesterol and triglyceride, and influences the higher content of cholesterol and triglyceride in blood lipid.
Experimental example 2
Platelet inhibition assay
Test sample: the pharmaceutical compositions for treating cardiovascular diseases prepared in examples 1 to 4 and comparative examples 1 to 3.
The testing method comprises the following steps: blood was collected from healthy volunteers using a 20mL syringe containing 2mL of buffered sodium citrate, transferred to polypropylene tubing, and centrifuged (100 g) at room temperature for 5 minutes (without the use of centrifuge braking), the surface-floating Platelet Rich Plasma (PRP) was collected, diluted, and platelet counted before it was used for aggregation measurement; measurement of platelet aggregation (platelet aggregation meter) was performed in glass tube at 37℃and 4. Mu.L of test sample was mixed with 392. Mu.L of freshly prepared PRP and incubated with stirring for 1 minute, 4. Mu.L of 250. Mu.M ADP solution was added to the mixture with continuous stirring, the change in optical density was recorded according to the method of G.V.R.born, the measurement of aggregation was monitored for 6-8min, the inhibition of platelets was expressed as IC50 (. Mu.M), and the greater the IC50, the greater the inhibition of platelets.
FIG. 4 is a graph showing the platelet inhibition results of examples 1 to 4 and comparative examples 1 to 3; as shown in the figure, the IC50 of examples 1-4 is 0.65-0.76. Mu.M, which shows that the platelet inhibition effect is strong and the antithrombotic effect is good; the IC50 of comparative examples 1-3 was 0.2-0.23. Mu.M, indicating weak platelet inhibition and poor antithrombotic effect; the pharmaceutical composition for treating cardiovascular diseases of comparative example 1 does not contain colon-targeted hydrogel, so that the bioavailability of the traditional Chinese medicine extract is reduced, and meanwhile, the oxidation resistance of lycopene is lacking, so that the effect of inhibiting platelets is influenced, and thrombus formation cannot be effectively prevented; the colon targeting hydrogel of comparative example 2 does not contain konjak fine powder, a targeted colon drug delivery path cannot be formed, the absorption of the traditional Chinese medicine extract is affected, the platelet inhibition effect is low, and the thrombus formation prevention effect is general; the colon targeting hydrogel of comparative example 3 does not contain chitosan, has reduced adsorptivity, and increases the risk of thrombosis due to higher cholesterol and triglyceride content in blood lipid.
Experimental example 3
Adverse reaction experiment
Test sample: the pharmaceutical compositions for treating cardiovascular diseases prepared in examples 1 to 4 and comparative examples 1 to 3.
The testing method comprises the following steps: clinical test volunteers 70 with ischemic cardiovascular disease were divided into 7 groups of 10 persons each, and after 5 days, the adverse reactions (in which gastrointestinal adverse reactions were manifested as nausea, vomiting, acid regurgitation, abdominal pain) were statistically analyzed.
FIG. 5 is a graph showing adverse reaction results of examples 1 to 4 and comparative examples 1 to 3; as shown in the figure, the frequency of the adverse reaction in examples 1-4 is 8-13, and the frequency is lower, which indicates that the adverse reaction is less; the adverse reaction frequency of comparative examples 1-3 is 52-55, and the frequency is high, which indicates that the adverse reaction is more; the pharmaceutical composition for treating cardiovascular diseases of comparative example 1 does not contain colon-targeted hydrogel, and the traditional Chinese medicine extract is released in the gastrointestinal tract, so that adverse reactions of the gastrointestinal tract are increased, and adverse reactions such as hypertension, hyperglycemia and the like can be possibly caused; the colon targeting hydrogel of the comparative example 2 does not contain konjak fine powder, has no colon targeting property, and increases adverse reaction of gastrointestinal tract; the colon targeting hydrogel of comparative example 3 does not contain chitosan, so that the stability of the hydrogel in the gastrointestinal tract is reduced, and the adverse reaction of the gastrointestinal tract is increased.
The experimental results show that the blood lipid content, the platelet inhibition effect and the gastrointestinal adverse reaction of the embodiment 1-4 are obviously superior to those of the sample of the comparative example 1-3, wherein the blood lipid of the embodiment 1 using colon-targeted hydrogel has lower cholesterol and triglyceride content, stronger platelet inhibition effect and fewer adverse reactions of the gastrointestinal tract, and salt ions, carboxymethyl konjak glucomannan and chitosan form inter-chain salt bonds, so that the molecular crosslinking effect is enhanced, the mechanical property of the co-coagulation gel is improved, the stability of the gastrointestinal tract is improved, the gastrointestinal tract is protected and the adverse reaction is reduced; the co-coagulation gel of the carboxymethyl konjak glucomannan and the chitosan has high specific surface area and high porosity, increases the adsorption quantity of single gel, strengthens the adsorption performance on harmful substances such as cholesterol, triglyceride, cholic acid and the like, inhibits the fat decomposed by the substances such as the cholesterol and the like from being absorbed by the small intestine and discharges the cholesterol out of the body; the carboxymethyl konjaku glucomannan has the colon targeting function, and the hydrogel adheres the traditional Chinese medicine extract on the surface of the colon, so that the traditional Chinese medicine extract stays for a long time, the concentration and the absorption of the traditional Chinese medicine extract are improved, and the bioavailability is further improved.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
The invention and its embodiments have been described above with no limitation, and the invention is illustrated in the figures of the accompanying drawings as one of its embodiments, without limitation in practice. In summary, those skilled in the art, having benefit of this disclosure, will appreciate that the invention can be practiced without the specific details disclosed herein.

Claims (8)

1. A pharmaceutical composition for treating cardiovascular disease, characterized in that: the pharmaceutical composition for treating cardiovascular diseases comprises the following components in parts by weight: 20-30 parts of colon-targeted hydrogel, 20-25 parts of campsis grandiflora, 20-25 parts of erigeron breviscapus, 20-25 parts of ligusticum chuanxiong, 15-20 parts of rhizoma sparganii, 10-15 parts of fingered citron, 10-15 parts of radix peucedani and 8-12 parts of lecithin; the colon targeting hydrogel comprises the following components in parts by weight: 5-8 parts of konjak fine powder, 15-20 parts of chitosan and 5-10 parts of lycopene.
2. A method of preparing a pharmaceutical composition for treating cardiovascular disease as claimed in claim 1, wherein: the method specifically comprises the following steps:
s1, soaking campsis grandiflora, erigeron breviscapus, ligusticum chuanxiong, rhizoma sparganii, fingered citron, citron and peucedanum praeruptorum in water in a decocting machine for 2-4 hours, decocting for 1-2 times, extracting for 2-3 hours by micro boiling, mixing decoctions, filtering, concentrating filtrate, vacuum pressure-0.06 MPa, temperature 50-55 ℃, drying at 40-50 ℃ for 20-25 minutes to obtain a traditional Chinese medicine extract;
s2, adding the colon-targeted hydrogel into water, heating and stirring, adding lecithin, continuously stirring, adding the traditional Chinese medicine extract in the step S1, uniformly stirring, drying at 40-50 ℃ for 20-30min, and obtaining the pharmaceutical composition for treating cardiovascular diseases.
3. The method for preparing a pharmaceutical composition for treating cardiovascular diseases according to claim 2, wherein: in the step S1, the weight ratio of the total weight of the campsis grandiflora, the erigeron breviscapus, the ligusticum chuanxiong, the rhizoma sparganii, the fingered citron, the citron and the peucedanum root to the water is 1:15.
4. A method of preparing a pharmaceutical composition for treating cardiovascular disease according to claim 3, wherein: in step S2, the weight ratio of the colon targeted hydrogel to water is 1:30-40.
5. The method for preparing a pharmaceutical composition for treating cardiovascular diseases according to claim 4, wherein: the preparation method of the colon-targeted hydrogel specifically comprises the following steps:
stirring konjak fine powder, adding into water, swelling for 0.5h, filtering to remove impurities, slowly adding a mixed solution of chloroacetic acid and potassium iodide according to a weight ratio of 6:1, reacting for 1-2h, taking out, cooling, adding an equal weight of acetone precipitate, filtering, repeatedly washing with an ethanol solution with a volume fraction of 80%, soaking with absolute ethanol overnight, drying at a constant temperature of 45-55 ℃ for 15-30min, and obtaining carboxymethyl konjak glucomannan;
(2) Dissolving chitosan in acetic acid solution with volume fraction of 1%, adding lycopene, stirring, heating in water bath to 50-60deg.C, adding sodium chloride solution with volume fraction of 1% -3% into chitosan acetic acid solution containing lycopene, and dissolving uniformly to obtain chitosan solution;
(3) Dissolving the carboxymethyl konjak glucomannan obtained in the step (1) in water to obtain carboxymethyl konjak glucomannan solution, heating in a water bath at 50-60 ℃, adding 1-3% by volume of sodium chloride solution into the carboxymethyl konjak glucomannan solution, uniformly dissolving, adding the chitosan solution obtained in the step (2), blending for 30min, and controlling the temperature at 60-70 ℃ to obtain the colon-targeted hydrogel.
6. The method for preparing a pharmaceutical composition for treating cardiovascular diseases according to claim 5, wherein: in the step (1), the weight ratio of the konjak fine powder to the water is 1:80-100; in the mixed solution of chloroacetic acid and potassium iodide, the volume fraction of chloroacetic acid is 1%, and the volume fraction of potassium iodide is 0.2%.
7. The method for preparing a pharmaceutical composition for treating cardiovascular diseases according to claim 6, wherein: in the step (2), the weight ratio of chitosan to acetic acid solution is 1:5-8; the weight ratio of the chitosan acetic acid solution containing lycopene to the sodium chloride solution is 15-20:1.
8. The method for preparing a pharmaceutical composition for treating cardiovascular diseases according to claim 7, wherein: in the step (3), the weight ratio of the carboxymethyl konjak glucomannan to the water is 1:10-15; the weight ratio of the carboxymethyl konjak glucomannan solution to the sodium chloride solution is 20-25:1.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101569641A (en) * 2008-04-30 2009-11-04 成都中医药大学 Medicine composition for treating ishemic stroke and preparation method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101569641A (en) * 2008-04-30 2009-11-04 成都中医药大学 Medicine composition for treating ishemic stroke and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
程绍恩;李树棠;于沧江;王岩枫;李海涛;: "理气行气法治疗冠心病57例", 上海中医药杂志, no. 08, 31 August 1981 (1981-08-31), pages 16 *

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