Traditional Chinese medicine granules with auxiliary blood pressure lowering effect and preparation method thereof

Abstract

The invention discloses traditional Chinese medicine granules with an auxiliary blood pressure lowering effect and a preparation method thereof. The traditional Chinese medicine granules are prepared by mixing uncaria, scutellaria baicalensis, semen cassiae, the root of kudzu vine, selfheal, leonurus, gastrodia elata, microcrystalline cellulose and a ginseng essential oil slow-release agent and then carrying out granulation and freeze-drying processes. Wherein the ginseng essential oil sustained-release agent is prepared by adopting ginseng essential oil and Tween 80 to form a nano microemulsion, then wrapping the nano microemulsion in a chitosan and sodium linoleate compound coating solution and performing freeze drying, and the ginseng essential oil sustained-release agent prepared in the mode can effectively prevent the ginseng essential oil from being in contact with oxygen to cause an oxidation phenomenon; the core functions of the ginseng essential oil sustained-release preparation are to control the release rate of active ingredients, reduce the administration frequency, maintain more stable blood concentration or active ingredient level, prolong the retention time of the medicine in gastrointestinal tracts, further promote absorption and improve the bioavailability.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine granule with auxiliary blood pressure lowering effect and a manufacturing method thereof. BACKGROUND

[0002] In recent years, with the acceleration of global aging and the change of residents' lifestyle, hypertension has become a major public health problem endangering human health. As a major risk factor for cardiovascular and cerebrovascular diseases, hypertension causes complications such as stroke, myocardial infarction and chronic kidney disease, which have high morbidity and mortality, and bring heavy medical burden to society and family.

[0003] At present, the commonly used antihypertensive drugs in clinical practice mainly include chemical drugs such as calcium channel blockers and angiotensin converting enzyme inhibitors. Although these drugs can effectively control blood pressure, long-term use may cause adverse reactions such as headache, dry cough and electrolyte imbalance. Moreover, some patients have poor drug compliance and unmet blood pressure control.

[0004] At the same time, traditional Chinese medicine has accumulated rich experience in the prevention and treatment of hypertension, but its preparation forms are mainly decoction and pills, which have inherent defects such as unstable effective components and low bioavailability, and cannot meet the demand of modern clinical practice for efficient, convenient and safe preparations. Especially for hypertensive patients who need long-term medication, the complex decoction process and taste of traditional Chinese medicine significantly affect the medication compliance, which restricts the promotion and application of traditional Chinese medicine in the field of auxiliary treatment of hypertension.

[0005] Under this background, in view of the limitations of existing antihypertensive drugs and the shortcomings of traditional Chinese medicine preparations, a kind of auxiliary antihypertensive traditional Chinese medicine granule based on modern pharmaceutical technology is developed. SUMMARY

[0006] The purpose of the present application is to provide a traditional Chinese medicine granule with auxiliary blood pressure lowering effect and a manufacturing method thereof.

[0007] The purpose of the present application can be achieved by the following technical solutions. A traditional Chinese medicine granule with auxiliary blood pressure lowering effect comprises the following raw materials in parts by weight: Uncaria 5-15 parts, Scutellaria 3-7 parts, Cassia seed 3-7 parts, Pueraria 10-20 parts, Prunella 10-20 parts, Motherwort 6-10 parts, Gastrodia 5-15 parts, microcrystalline cellulose 1-3 parts, ginseng essential oil sustained-release agent 1-3 parts. Uncaria belongs to Rubiaceae, has sweet and cool properties, and is meridian-entering liver and pericardium. The main components are alkaloids, triterpenes, flavonoids and esters, etc., and Uncaria has the effects of lowering blood pressure, reducing heart rate, inhibiting myocardial hypertrophy and anti-tumor, etc.

[0008] Scutellaria Baicalensis Georgi is a Labiatae plant, with cold medicinal properties, bitter and flat taste, entering the heart, lung, gallbladder and large intestine channels, with the effects of clearing heat and drying dampness, purging fire and detoxifying, stopping bleeding and preventing miscarriage. Its main active components flavonoids such as baicalin, baicalein and wogonin can dilate blood vessels, inhibit the renin-angiotensin system, and have antioxidant and anti-inflammatory effects, diuresis and blood pressure-lowering effects.

[0009] Semen Cassiae is the dried mature seeds of Cassia obtusifolia or Senna tora, with sweet, bitter, salty and cold medicinal properties, and belongs to the liver and large intestine channels. Its main active components include chrysophanol and emodin, which can dilate blood vessels and lower blood viscosity to lower blood pressure.

[0010] Radix Puerariae is the dried root of Pueraria lobata, with sweet, pungent and cool medicinal properties, and belongs to the spleen and stomach channels. It has the effects of relieving the exterior and reducing fever, promoting fluid production and quenching thirst, promoting rash, ascending yang and stopping diarrhea, and activating meridians. Its active component puerarin can enhance the vasodilation function of vascular endothelial cells, promote the proliferation and migration of endothelial cells, directly lower blood pressure, protect blood vessels from damage, and reduce the risk of cardiovascular complications caused by high blood pressure.

[0011] Prunella vulgaris is a Labiatae plant, with bitter, pungent and cold medicinal properties, and belongs to the liver and gallbladder channels. It has the effects of clearing heat, improving eyesight, resolving masses and reducing swelling, and is commonly used to treat liver and gallbladder diseases, reduce blood pressure, regulate blood pressure, and prevent and treat pulmonary tuberculosis.

[0012] Leonurus japonicus is a Labiatae plant, with bitter, pungent and cold medicinal properties, and belongs to the liver, pericardium and bladder channels. It has the effects of promoting blood circulation and regulating menstruation, reducing blood pressure, and removing blood stasis to promote blood flow. It can treat primary hypertension through blood activation, water reduction and blood pressure reduction.

[0013] Gastrodia elata is a Gastrodia elata plant, with sweet and neutral medicinal properties, and belongs to the liver channel. It has the effects of lowering blood pressure, reducing peripheral vascular resistance, and improving vascular compliance. It can effectively lower blood pressure while significantly improving clinical symptoms such as dizziness and headache, reducing target organ damage, and reducing the occurrence of adverse cardiovascular events.

[0014] The above traditional Chinese medicinal materials and microcrystalline cellulose are combined with ginseng essential oil sustained-release agents to form a traditional Chinese medicine granule with high blood pressure-lowering effect through the synergistic effect of the components.

[0015] Further, the preparation method of the ginseng essential oil sustained-release agent includes the following steps: A1: Add chitosan powder to glacial acetic acid solution and continuously stir to prepare a chitosan stock solution; A2: Add sodium linoleate to deionized water and continuously stir to prepare a sodium linoleate stock solution; A3: Mix the chitosan stock solution and the sodium linoleate stock solution, adjust the pH of the solution to neutral, and stir at room temperature to obtain a coating solution. A4: Ginseng essential oil is mixed with emulsifier Tween 80, added to deionized water, and stirred continuously to form a ginseng essential oil microemulsion; A5: The ginseng essential oil microemulsion is added to the coating liquid and stirred vigorously to form a nanosuspension; A6: The suspension is placed in a freeze dryer and freeze-dried to obtain a ginseng essential oil sustained-release preparation.

[0016] Further, in step A1, the volume fraction of glacial acetic acid solution is 1-2%, and the mass concentration of chitosan stock solution is 10-20%.

[0017] Further, in step A2, the mass concentration of sodium linoleate stock solution is 5-15%. A sodium linoleate stock solution concentration <5% will result in a decrease in stability, and a sodium linoleate stock solution concentration >15% will cause crystallization at room temperature, affecting the stability of the stock solution.

[0018] Further, in step A3, the volume ratio of chitosan stock solution to sodium linoleate stock solution is 1:0.5-1.

[0019] Further, in step A4, the amount of Tween 80 is 20%-50% of the mass of ginseng essential oil.

[0020] Through the above technical solution, chitosan has a positive charge and can produce electrostatic effects with negatively charged sodium linoleate, attracting each other to form a complex. The hydrophilic polyoxyethylene group in the structure of Tween 80 binds with water, and the hydrophobic fatty acid chain of ginseng essential oil component binds, forming nanoscale droplets and stably dispersing by reducing the oil-water interfacial tension; then the microemulsion is introduced into the chitosan-sodium linoleate coating liquid and stirred vigorously, and the coating complex is adsorbed on the surface of the ginseng essential oil droplets by the lipophilic effect of the long fatty chain, forming a single-layer coating, and the protonated amino groups of chitosan and the linoleate anion are further crosslinked by ionic bonds or hydrogen bonds, enhancing the compactness of the coating layer, while mechanical stirring promotes uniform coating to form a stable nanosuspension. Through the freeze-drying process, the coating layer is solidified into a porous network structure, and the ginseng essential oil is sealed in the cavities formed by the chitosan-sodium linoleate complex to form a ginseng essential oil sustained-release preparation.

[0021] A manufacturing method of a traditional Chinese medicine granule with auxiliary blood pressure lowering effect, comprising the following steps: First step: screen the Uncaria, Scutellaria, Cassia seed, Pueraria, Prunella vulgaris, and Gastrodia elata, remove insect pests and impurities, wash and dry, then crush and pass through a sieve to obtain a standby material; Second step: mix the standby material, ginseng essential oil sustained-release preparation, and microcrystalline cellulose, add to an ethanol aqueous solution, and put into a fluidized bed granulator to granulate by top spraying; Third step: dry the wet granules in a freeze dryer, sieve the dried granules to uniform size, seal with aluminum plastic film, and it is ready.

[0022] Further, in the second step, the volume fraction of the ethanol aqueous solution is 60-70%.

[0023] Further, in the third step, the freeze drying temperature is -20℃ to -25℃, and the mesh sieve is 100-120 mesh.

[0024] The beneficial effects of the present application are: (1) The present application uses mild Chinese medicine for combination, utilizes the effective components of each medicinal material to produce synergistic effect, so that the prepared granules are mild and non-irritating, and have good blood pressure lowering effect.

[0025] (2) The present application uses ginseng essential oil and Tween 80 to form a nano microemulsion, which is then coated in a chitosan-sodium linoleate complex coating solution, and then freeze-dried to prepare a ginseng essential oil sustained-release preparation. Since ginseng essential oil contains various active ingredients such as ginsenosides and volatile oils, these components are easily oxidized by oxygen. By wrapping them in a chitosan-sodium linoleate coating solution to form a nano-suspension, oxygen can be effectively isolated, oxidation and volatilization can be reduced, and the problem of instability of ginseng essential oil active ingredients can be solved. In addition, the core function of the ginseng essential oil sustained-release preparation is to control the release rate of the active ingredients. Chitosan, as a natural polymer material, has biological adhesion and excellent sustained-release properties. When the ginseng essential oil microemulsion is wrapped in the chitosan matrix, its release rate can be regulated by the degradation rate of chitosan. This sustained-release effect can prolong the residence time of ginseng essential oil in the body, reduce the frequency of administration, maintain a more stable blood drug concentration or active ingredient level, prolong the residence time of the drug in the gastrointestinal tract, further promote absorption, and improve bioavailability.

[0026] Of course, implementing any product of the present application does not necessarily require all the advantages described above. DETAILED DESCRIPTION

[0027] The technical solutions in the embodiments of the present application will be described below in conjunction with the embodiments, obviously, the described embodiments are only a part of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor belong to the scope of protection of the present application.

[0028] Embodiment 1 A traditional Chinese medicine granule with auxiliary blood pressure lowering effect, comprising the following raw materials in parts by weight: Uncaria 5 parts, Scutellaria 3 parts, Cassia seed 3 parts, Pueraria 10 parts, Prunella 10 parts, Motherwort 6 parts, Gastrodia 5 parts, microcrystalline cellulose 1 part, and ginseng essential oil sustained-release preparation 1 part.

[0029] The preparation method of the traditional Chinese medicine granules comprises the following steps: First step: screen Gouteng, Huangqi, Juemingzi, Gegen, Xiaakucao, Yimucao and Tianma, remove insect pests and impurities, wash and dry, then crush and pass through a sieve to obtain standby materials; Second step: mix the above standby materials, ginseng essential oil sustained-release agent and microcrystalline cellulose, add to an ethanol aqueous solution with a volume fraction of 60%, and put into a fluidized bed granulator to granulate by top spraying; Third step: dry the wet granules in a freeze-drying machine at-20℃, then pass the granules through a 100-mesh sieve to size, seal with aluminum plastic film, and the granules are ready.

[0030] The preparation method of the ginseng essential oil sustained-release agent comprises the following steps: A1: add chitosan powder to an ice acetic acid solution with a volume fraction of 1%, continuously stir, and prepare a chitosan stock solution with a mass concentration of 10%; A2: add sodium linoleate to deionized water, continuously stir, and prepare a sodium linoleate stock solution with a mass concentration of 5%; A3: mix 80mL of the chitosan stock solution with 40mL of the sodium linoleate stock solution, adjust the pH of the solution to neutral, and stir at room temperature to obtain a coating solution; A4: mix 2g of ginseng essential oil with 1g of emulsifier Tween 80, add to 100mL of deionized water, continuously stir, and form a ginseng essential oil microemulsion; A5: add 50mL of the ginseng essential oil microemulsion to 100mL of the coating solution, continuously stir vigorously, and form a nanosuspension; A6: place the suspension in a freeze-drying machine, freeze-dry, and obtain the ginseng essential oil sustained-release agent.

[0031] Example 2 A traditional Chinese medicine granule with auxiliary blood pressure lowering effect comprises the following raw materials in parts by weight: Gouteng 10 parts, Huangqi 4 parts, Juemingzi 6 parts, Gegen 15 parts, Xiaakucao 13 parts, Yimucao 8 parts, Tianma 11 parts, microcrystalline cellulose 2 parts, and ginseng essential oil sustained-release agent 2.5 parts.

[0032] The preparation method of the traditional Chinese medicine granules comprises the following steps: First step: screen Gouteng, Huangqi, Juemingzi, Gegen, Xiaakucao, Yimucao and Tianma, remove insect pests and impurities, wash and dry, then crush and pass through a sieve to obtain standby materials; Second step: mix the above standby materials, ginseng essential oil sustained-release agent and microcrystalline cellulose, add to an ethanol aqueous solution with a volume fraction of 65%, and put into a fluidized bed granulator to granulate by top spraying; Third step: the wet granules are placed in a freeze dryer at -20℃ for drying, then the granules are sieved through a 100 mesh sieve for granulation, sealed with aluminum plastic film, and ready.

[0033] The preparation method of the ginseng essential oil sustained-release agent is the same as that in Embodiment 1.

[0034] Embodiment 3 A traditional Chinese medicine granule with auxiliary blood pressure lowering effect comprises the following raw materials in parts by weight: Gouteng 15 parts, Huangqi 7 parts, Juemingzi 7 parts, Gegen 20 parts, Xiaakucao 20 parts, Yimucao 10 parts, Tianma 15 parts, microcrystalline cellulose 3 parts, and ginseng essential oil sustained-release agent 3 parts.

[0035] The preparation method of the traditional Chinese medicine granule comprises the following steps: First step: Gouteng, Huangqi, Juemingzi, Gegen, Xiaakucao, Yimucao, and Tianma are screened to remove diseased and insect-damaged plants and impurities, washed, dried, crushed, and sieved through a mesh sieve to obtain standby materials; Second step: the standby materials, ginseng essential oil sustained-release agent, and microcrystalline cellulose are mixed, added to an ethanol aqueous solution with a volume fraction of 70%, and put into a fluidized bed granulator for granulation by a top spraying method; Third step: the wet granules are placed in a freeze dryer at -20℃ for drying, then the granules are sieved through a 120 mesh sieve for granulation, sealed with aluminum plastic film, and ready.

[0036] The preparation method of the ginseng essential oil sustained-release agent is the same as that in Embodiment 1.

[0037] Comparative Example 1 A traditional Chinese medicine granule with auxiliary blood pressure lowering effect comprises the following raw materials in parts by weight: Gouteng 10 parts, Huangqi 5 parts, Juemingzi 5 parts, Gegen 15 parts, Xiaakucao 15 parts, Yimucao 8 parts, Tianma 10 parts, microcrystalline cellulose 2 parts, and ginseng essential oil 2 parts.

[0038] The preparation method of the traditional Chinese medicine granule comprises the following steps: First step: Gouteng, Huangqi, Juemingzi, Gegen, Xiaakucao, Yimucao, and Tianma are screened to remove diseased and insect-damaged plants and impurities, washed, dried, crushed, and sieved through a mesh sieve to obtain standby materials; Second step: the standby materials, ginseng essential oil, and microcrystalline cellulose are mixed, added to an ethanol aqueous solution with a volume fraction of 65%, and put into a fluidized bed granulator for granulation by a top spraying method; Third step: the wet granules are placed in a freeze dryer at -20℃ for drying, then the granules are sieved through a 100 mesh sieve for granulation, sealed with aluminum plastic film, and ready.

[0039] Comparative Example 2 A traditional Chinese medicine granule with auxiliary blood pressure lowering effect, comprising the following raw materials in parts by weight: Uncaria 10 parts, Scutellaria 5 parts, Cassia seed 5 parts, Pueraria 15 parts, Prunella 15 parts, Motherwort 8 parts, Gastrodia 10 parts, and microcrystalline cellulose 2 parts.

[0040] The preparation method of the traditional Chinese medicine granule comprises the following steps: First step: Uncaria, Scutellaria, Cassia seed, Pueraria, Prunella, Motherwort, and Gastrodia are screened to remove insect pests, diseased strains, and impurities, washed, dried, then crushed and passed through a sieve, to obtain standby material; Second step: the standby material is mixed with microcrystalline cellulose, added to an ethanol aqueous solution with a volume fraction of 65%, and put into a fluidized bed granulator to granulate by top spraying; Third step: the wet granules are dried in a freeze dryer at -20℃, then sieved through a 100-mesh sieve to size the granules, sealed with aluminum plastic film, and ready.

[0041] Test example (1) Blood pressure lowering effect test: 75 SPF level SHR male rats weighing 180-200 g were selected, adaptively fed for one week, and the systolic pressure was detected by continuous 3-day tail artery pressure measurement method to confirm the success of modeling.

[0042] The 70 successfully modeled rats were divided into 7 groups, 10 rats in each group, namely Example 1 group-Example 3 group, Comparative Example 1 group-Comparative Example 2 group, and a blank control group.

[0043] The traditional Chinese medicine granules obtained from Example 1 group-Example 3 group and Comparative Example 1 group-Comparative Example 2 group were weighed, and the same amount of water was added for decoction to prepare a drug solution with a mass concentration of 2 mg / mL. Then, based on the weight of the animals, 5 mL / kg of the drug solution was administered by gavage. The blank control group was given the corresponding volume of normal saline by gavage.

[0044] Each group was given gavage once a day, continuously for 1 week, and the next day before administration, the blood pressure was measured by vBP-6 animal non-invasive blood pressure determination instrument. The systolic pressure of the rats was measured in a clear and non-angry state in an environment of 25℃, and the mean value was taken after continuous measurement for 3 times. The test results are shown in Table 1:

[0045] Note: # indicates comparison with the blank control group, P<0.01 According to the analysis of the test results, the traditional Chinese medicine granules prepared in the embodiment have good blood pressure lowering effect. The sustained release effect cannot be produced after replacing the ginseng essential oil sustained release agent with the ginseng essential oil, because the ginseng essential oil is encapsulated in the coating liquid, which can effectively isolate oxygen, reduce the oxidation and volatilization of active ingredients, and improve the stability of the drug, thereby effectively exerting the sustained release effect, and avoiding the occurrence of blood pressure fluctuation caused by rapid metabolism of ordinary uncoated ginseng essential oil.

[0046] (2) Stability test: The same weight of traditional Chinese medicine granules in example 1 group to example 3 group and comparative example 1 group was taken, and the influence factor test was carried out according to the test method of appendix XIX C in Chinese Pharmacopoeia 2010 edition part 2.

[0047] Three samples of example 1 group to example 3 group and comparative example 1 group were taken and placed in a 25℃ constant temperature box, and samples were taken after three months. The content of ginsenoside, the main component of ginseng essential oil, was measured by GC method.

[0048] The average value of each group of experimental values is as follows:

[0049] According to the analysis of the test results, the ginseng essential oil sustained release agent prepared in the embodiment can encapsulate the ginseng essential oil in the coating liquid, effectively isolate air, improve the stability of the active ingredients of ginseng essential oil, and lay a foundation for the subsequent traditional Chinese medicine granules of the application to effectively lower blood pressure.

[0050] The above content is only an example and description of the concept of the application, and those skilled in the art can make various modifications or supplements or use similar ways to replace the described specific embodiments, as long as they do not deviate from the concept of the application or exceed the scope defined by the claims, which should belong to the protection scope of the application.

Claims

1. A traditional Chinese medicine granule having an auxiliary blood pressure lowering effect, characterized in that, The raw materials include the following components in parts by weight: Uncaria 5-15 parts, Scutellaria 3-7 parts, Cassia seed 3-7 parts, Pueraria 10-20 parts, Prunella 10-20 parts, Motherwort 6-10 parts, Gastrodia 5-15 parts, microcrystalline cellulose 1-3 parts, ginseng essential oil sustained-release agent 1-3 parts.

2. The traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 1, characterized in that, The preparation method of the ginseng essential oil sustained-release agent comprises the following steps: A1: adding chitosan powder into glacial acetic acid solution, continuously stirring, and configuring into chitosan stock solution; A2: adding sodium linoleate into deionized water, continuously stirring, and configuring into sodium linoleate stock solution; A3: mixing the chitosan stock solution and the sodium linoleate stock solution, adjusting the pH of the solution to neutral, and stirring at room temperature to obtain a coating liquid; A4: mixing ginseng essential oil and emulsifier Tween 80, adding into deionized water, continuously stirring, and forming ginseng essential oil microemulsion; A5: adding the ginseng essential oil microemulsion into the coating liquid, continuously stirring, and forming nanosuspension; A6: placing the suspension in a freeze dryer, freeze-drying, and obtaining the ginseng essential oil sustained-release agent.

3. The traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 2, characterized in that, In the step A1, the volume fraction of the glacial acetic acid solution is 1-2%, and the mass concentration of the chitosan stock solution is 10-20%.

4. The traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 2, characterized in that, In the step A2, the mass concentration of the sodium linoleate stock solution is 5-15%.

5. The traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 2, characterized in that, In the step A3, the volume ratio of the chitosan stock solution to the sodium linoleate stock solution is 1:0.5-1.

6. The traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 2, characterized in that, In the step A4, the amount of Tween 80 is 20-50% of the mass of the ginseng essential oil.

7. The method for manufacturing the traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 1, characterized in that, The method comprises the following steps: First step: screening Uncaria, Scutellaria, Cassia seed, Pueraria, Prunella, Motherwort and Gastrodia, removing insect pests and impurities, washing, drying, then crushing and passing through a sieve to obtain standby materials; Second step: mixing the standby materials, ginseng essential oil sustained-release agent and microcrystalline cellulose, adding into an ethanol aqueous solution, and feeding into a fluidized bed granulator to granulate by top spraying; Third step: drying the wet granules in a freeze dryer, sieving the dried granules to whole granules, sealing with aluminum plastic film, and obtaining the granules.

8. The manufacturing method of the traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 7, characterized in that, In the second step, the volume fraction of the ethanol aqueous solution is 60-70%.

9. The manufacturing method of the traditional Chinese medicine granules with auxiliary blood pressure lowering effect according to claim 7, characterized in that, In the third step, the freeze-drying temperature is-20℃ to-25℃, and the sieve is 100-120 meshes.

Images