CN107260963B - Method for preparing medicine for treating hypertension by using dendrobium officinale and radish seed as main materials - Google Patents

Method for preparing medicine for treating hypertension by using dendrobium officinale and radish seed as main materials Download PDF

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CN107260963B
CN107260963B CN201710453864.2A CN201710453864A CN107260963B CN 107260963 B CN107260963 B CN 107260963B CN 201710453864 A CN201710453864 A CN 201710453864A CN 107260963 B CN107260963 B CN 107260963B
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blood pressure
dendrobium officinale
hypertension
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CN107260963A (en
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吴人照
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Hangzhou Dan he Pharmaceutical Co., Ltd.
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    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
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    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

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Abstract

The invention relates to a medicine preparation technology, and aims to provide a method for preparing a medicine for treating hypertension by using dendrobium officinale and radish seed as main materials. The method comprises the following steps: grinding parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba respectively, mixing, extracting with hot water, and concentrating to obtain water extract concentrate; grinding herba Dendrobii into powder, and adding into the concentrated water extract; adding auxiliary materials and forming. Or grinding the four medicinal materials into powder, and then carrying out alcohol extraction: adding 75% ethanol 5 times of the crude drug, extracting at 60 deg.C for 24 hr for 2 times, and recovering ethanol; after alcohol extraction, the residue is further treated with water extraction, concentrated and the extracted liquid is combined. Adding auxiliary materials and forming. The medicine prepared by the invention is suitable for treating hypertension with yin deficiency or yin deficiency and yang hyperactivity, accompanied by restlessness of heart and insomnia; or the western medicine antihypertensive drug is used together for treatment, so that the dosage of the western medicine antihypertensive drug is reduced. It is also suitable for patients with mild hypertension or normal hypertension.

Description

Method for preparing medicine for treating hypertension by using dendrobium officinale and radish seed as main materials
Technical Field
The invention relates to a medicine preparation technology, in particular to a method for preparing a medicine for treating hypertension by taking dendrobium officinale and radish seed as main materials and application thereof.
Background
Hypertension is a common clinical high incidence disease and has serious harm to heart, brain, kidney and other important organs. According to the 'Chinese cardiovascular disease report' in 2013 years in China, about 2.7 hundred million hypertension patients in China are estimated at present. 2012. The 'report on cardiovascular diseases in China' in 2013 shows that: the mortality rate of cardiovascular diseases in China is 44.1%, and the disease is the first in the death disease spectrum. Hypertension is the leading cause of cardiovascular and cerebrovascular diseases. Epidemic disease survey results show that the fatality rate of cardiovascular and cerebrovascular diseases caused by hypertension in China is increased year by year, as for cerebral apoplexy, 160 more than ten thousand people suffer from cerebral apoplexy every year in China, about 600 ten thousand people accumulate survivors, wherein more than 75 percent of people lose labor force, 45 percent of people are severely disabled, and life cannot be taken care of by oneself.
Western medicines for treating hypertension lack medicines capable of regulating physique and regulating blood pressure (lowering blood pressure). The pressure reduction treatment in modern medicine is symptomatic treatment. The blood pressure lowering drugs commonly used at present comprise 5 types of Calcium Channel Blockers (CCB), Angiotensin Converting Enzyme Inhibitors (ACEI), angiotensin II receptor blockers (ARB), diuretics and beta blockers, and can not completely prevent the development of hypertension and the secondary diseases thereof. Most of the patients with hypertension need 2 or more antihypertensive medicines to reach the target blood pressure or are difficult to reach the target blood pressure, most of the patients need to take the medicine for life, the curative effect of the medicine is gradually reduced due to long-term administration, toxic and side effects are generated, and the problems are more prominent along with the prolonging of the service life. There is still a pressing need for new and more sophisticated therapeutic agents for the treatment of hypertension.
The existing traditional Chinese medicine conditioning method has certain advantages when being used for treating hypertension, but has serious defects. Although the traditional Chinese medicine can regulate hypertension, the blood pressure reducing speed and amplitude are not as fast as those of western medicines, the traditional Chinese medicine has the advantages of more stable and lasting curative effect, small blood pressure rise amplitude after medicine stopping, and the blood pressure control and the improvement of the whole body constitution. Or the health-care tea can regulate and reduce blood pressure and blood fat, has the advantages of adjusting the physique, improving various pathological indexes after improving the physique and has certain application value. However, the recent blood pressure reduction is not obvious enough after the medicine is taken, the medicines have too many flavors and mutually restrict or offset the effect, the medicine formula, extraction, preparation process and the like are not optimized systematically, the curative effect cannot meet the requirement, and the medicine has practical application value in clinic.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defects in the prior art and provides a method for preparing a medicine for treating hypertension by using dendrobium officinale and radish seed as main materials and application thereof.
In order to solve the technical problem, the solution of the invention is as follows:
provides a method for preparing a medicine for treating hypertension by utilizing dendrobium officinale and radish seeds, which comprises the following steps:
(1) according to the requirements of 2015 version of Chinese pharmacopoeia, taking 2.5-15 parts of dendrobium officinale, 2.5-60 parts of fried radish seeds, 2.5-15 parts of radix ophiopogonis and 2.5-15 parts of radix paeoniae alba, wherein the parts are parts by weight;
(2) grinding parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba respectively, mixing, extracting with hot water, and concentrating to obtain water extract concentrate;
(3) grinding herba Dendrobii into powder, and adding into the concentrated water extract; then adding auxiliary materials according to a conventional pharmaceutical processing method, and preparing into traditional Chinese medicine tablets, granules, pills or capsules to obtain the medicine for treating hypertension.
The invention further provides a using method of the hypertension drug prepared by the method, the prepared traditional Chinese medicine tablet, granule, pill or capsule is orally taken, and the daily dosage of the traditional Chinese medicine tablet, granule, pill or capsule is equivalent to 10g to 105g of crude drug for an adult.
The invention also provides application of the hypertension drug prepared by the method as health food, wherein the traditional Chinese medicine tablet, granule, pill or capsule is used as the health food in an oral administration mode, and the daily dosage of an adult is equivalent to 10g to 105g of crude drug.
The invention also provides another method for preparing a medicine for treating hypertension by utilizing dendrobium officinale and radish seeds, which comprises the following steps:
(1) according to the requirements of 2015 version Chinese pharmacopoeia, taking 5-30 parts of dendrobium officinale, 5-120 parts of fried radish seed, 5-30 parts of radix ophiopogonis and 5-30 parts of white paeony root, wherein the parts are parts by weight;
(2) grinding the four medicinal materials into powder, and then carrying out alcohol extraction: adding 75% ethanol 5 times of the crude drug, extracting at 60 deg.C for 24 hr for 2 times, and recovering ethanol; after alcohol extraction, the residue is further treated with water extraction, concentrated and the extracted liquid is combined.
(3) Adding adjuvants according to conventional pharmaceutical processing method, and making into Chinese medicinal tablet, granule, pill or capsule to obtain medicine for treating hypertension.
In the invention, the water extraction is twice gradient heating water extraction; wherein the extraction temperature is controlled to be 100 ℃ in the first water extraction, 121 ℃ in the second water extraction, and the two extraction solutions are combined.
The invention further provides a using method of the hypertension drug prepared by the method, the prepared traditional Chinese medicine tablet, granule, pill or capsule is orally taken, and the daily dosage of the traditional Chinese medicine tablet, granule, pill or capsule is equivalent to 10g to 150g of crude drug for an adult.
The invention also provides application of the hypertension drug prepared by the method as health food, which is characterized in that the traditional Chinese medicine tablet, granule, pill or capsule is taken as the health food in an oral way, and the daily dosage of an adult is equivalent to 10g to 150g of crude drug.
The realization principle of the invention is as follows:
in the theory of traditional Chinese medicine, hypertension is considered to be mostly due to yin deficiency and yang hyperactivity, i.e. yin deficiency with excessive ascending of yang qi, i.e. qi activity with residual and insufficient descending. Meanwhile, most patients are also accompanied by phlegm-dampness, obesity (hyperlipidemia), restlessness of heart-mind, insomnia, etc. Nourishing yin and suppressing yang, directing qi downward and resolving phlegm, clearing heart fire and tranquilizing mind are the main therapeutic directions.
According to the theory and practice of traditional Chinese medicine, according to the record of the pharmacopoeia of the people's republic of China 2015 edition: the dendrobium officinale has the functions of tonifying stomach, promoting fluid production, nourishing yin and clearing heat. Can be used for treating fever with body fluid deficiency, dry mouth, polydipsia, stomach yin deficiency, anorexia, retching, persistent asthenic fever after illness, yin deficiency, hyperactivity of fire, bone steaming, overstrain, dim and poor vision, and flaccidity of tendons and bones. The prior art is also useful for the treatment of hypertension, but it has not been applied on a large scale because of its slower onset of action. The parched Raphani semen has the effects of resolving food stagnation, relieving flatulence, descending qi and eliminating phlegm, and can be used for treating food stagnation, abdominal distention and pain, constipation, stagnation and dysentery, phlegm accumulation and cough and asthma. However, the application of the two traditional Chinese medicines in treating hypertension is as follows: only dendrobium officinale has the effects of nourishing yin and clearing heat, but does not have the effect of guiding qi movement downwards, so that the effect of reducing blood pressure is limited, and only radish seed has the effects of reducing qi and reducing phlegm, but does not have the effect of nourishing yin to suppress yang, so that the effect of reducing blood pressure is also limited. Consider generally: the radish seeds are qi-moving and stasis-resolving medicines which are generally not used together with tonifying traditional Chinese medicines, and if the qi-moving and stasis-resolving medicines such as the radish seeds are used for a long time, excessive consumption is caused, so that people worry about the obstruction of physique improvement and hypertension rehabilitation. The invention creatively combines the two medicines to nourish yin and suppress yang, and simultaneously guide qi movement to descend, and adopts a proper proportion formula and a proper preparation process, so that the blood pressure reducing effect is greatly improved, the conventional concept is broken through, and an unexpected curative effect is obtained.
According to the theory and practice of traditional Chinese medicine, according to the record of the pharmacopoeia of the people's republic of China 2015 edition: the radix ophiopogonis has the functions of nourishing yin, promoting the production of body fluid, moistening lung and clearing heart fire, and is used for lung dryness, dry cough, yin deficiency tuberculosis cough, throat impediment, sore throat, body fluid consumption, thirst, internal heat, diabetes, vexation, insomnia and intestinal dryness constipation. The properties of the white peony root are nourishing blood, regulating menstruation, astringing yin, arresting sweating, softening liver, relieving pain and calming liver yang. Can be used for treating blood deficiency, sallow complexion, menoxenia, spontaneous perspiration, night sweat, hypochondriac pain, abdominal pain, limb spasm pain, headache, and vertigo. The application of the two traditional Chinese medicines in treating hypertension is as follows: radix ophiopogonis has no literature report of being used for treating hypertension alone, radix paeoniae alba is used for reducing blood pressure alone and has few literature reports, radix paeoniae alba can be used for nourishing blood and softening liver and treating headache, dizziness and other diseases caused by blood deficiency and liver excess, and the traditional application is indirectly related to modern hypertension treatment. The invention creatively combines the dendrobium officinale and the stir-fried radish seed into the formula of the dendrobium officinale and the stir-fried radish seed, thereby enhancing the effects of nourishing yin and clearing heat, and increasing the effects of nourishing blood and liver and clearing away heart fire and tranquilizing mind. The four traditional Chinese medicine formulas are matched, so that the four traditional Chinese medicine formulas not only can nourish yin and suppress yang and guide qi movement to descend so as to reduce blood pressure, but also can nourish blood and soften liver, clear heart and tranquilize mind so as to promote blood pressure to be stable, form virtuous circulation and be beneficial to blood pressure recovery of patients with restlessness and insomnia.
The invention innovatively provides two schemes for preparing the medicine for treating the hypertension, and the obtained medicine is suitable for treating the hypertension of yin deficiency syndrome or yin deficiency and yang excess syndrome and is accompanied with the treatment of patients with restlessness of heart and insomnia; or the western medicine antihypertensive drug is used together for treatment, so that the dosage of the western medicine antihypertensive drug is reduced. Meanwhile, the two medicines are also suitable for the health care of patients with mild hypertension or normal hypertension. More importantly, the traditional Chinese medicine for treating hypertension generally has the problems of unsatisfactory blood pressure reducing effect in the aspect of curative effect, low blood pressure effect taking speed and difficulty in stabilizing blood pressure fluctuation of hypertension patients with restless mind and insomnia, and the medicine disclosed by the invention can obtain a curative effect similar to that of western medicine antihypertensive medicines and has the effects of nourishing blood, softening liver, clearing heart and soothing nerves. This is a very significant and unexpected technical effect that breaks through imagination.
The difference between the two schemes is: the final obtained medicine is smaller in volume by adopting a treatment scheme of carrying out alcohol-water extraction (including two times of gradient water extraction) on four Chinese medicinal materials, can use larger crude drug quantity to improve the curative effect, and is convenient to take. However, the adoption of the water extraction treatment scheme (grinding dendrobium officinale into powder) for only radish seeds, ophiopogon roots and white paeony roots relatively saves medicinal materials.
It should be noted that, in view of the homology between traditional Chinese medicine and health food, in most cases, the traditional Chinese medicine and the health food are only different in national management categories, and their substantial contents are basically even completely the same. The product of the invention also belongs to the condition, can be used as a traditional Chinese medicine for treating hypertension, and can also be used for daily health care of patients with mild hypertension or normal partial hypertension, and the using methods in the two conditions are the same.
Compared with the prior art, the invention has the beneficial effects that:
1. the dendrobium officinale, in combination with the stir-fried radish seeds, the radix ophiopogonis and the white paeony root, can treat both symptoms and root causes of hypertension, and has the advantages of remarkable curative effect: dendrobium officinale Kimura et Migo is a method for treating the root cause of yin deficiency and yang hyperactivity by nourishing yin to suppress yang; the stir-baked radish seed has the effects of depressing qi, guiding qi and blood downward and resolving phlegm-dampness, and is a method for treating both principal and secondary aspect of disease. The two medicines are used together, so that the curative effect of reducing blood pressure can be achieved quickly, and good physique of stabilizing blood pressure in middle and long periods and adjusting and recovering the lifting balance can be obtained. And radix Ophiopogonis and radix Paeoniae alba can tranquilize mind, nourish liver and soften liver, and promote qi flow to restore balance. The formula can obtain the unexpected curative effect similar to that of western medicine antihypertension drugs.
2. Selectively regulating hypertension patients without affecting normal blood pressure: it has blood pressure lowering effect on hypertension, but has no blood pressure lowering effect on normal blood pressure. Nor will hypertension be reduced below normal. The traditional Chinese medicine composition has the advantages of being compared with most western medicine antihypertensive medicines.
3. In the extraction scheme of the invention, the traditional Chinese medicine powder is prepared into tablets, pills and capsules, which are beneficial to exerting lasting and stable drug effect: (1) the hypertension treatment requires the medicine to exert lasting and stable drug effect, the western medicine hypotensor adopts a sustained release formulation, the invention adopts the medicinal material fine powder to prepare tablets, pills and capsules so as to exert the slow release of the pills in the traditional Chinese medicine, so that the medicine is gradually dissolved out to exert the effect and the lasting and stable drug effect is achieved; (2) raw dendrobium officinale (different from long-time decoction) by grinding into powder: also has better functions of clearing heat and reducing internal heat, and is beneficial to the rapid reduction of blood pressure; (3) the dendrobium officinale is an expensive medicinal material and needs to be fully utilized: the technical scheme of the invention fully considers the utilization of the noble medicinal materials of the dendrobium officinale, reduces the waste caused by incomplete extraction, and simultaneously reduces the damage of partial components in the heating extraction process so as to improve the curative effect and save the noble medicinal materials.
4. In the ethanol extraction and water extraction scheme of the invention, (1) the comprehensive extraction method can reduce the loss of components and improve the effectiveness compared with the conventional water extraction: grinding all the medicinal materials, and increasing contact surface for extraction; the ethanol extraction is firstly carried out to ensure that the alcohol-soluble substances are dissolved out at a lower temperature, the ethanol extraction is carried out and then the water extraction is carried out, the alcohol-soluble substances are not in the water extraction, the heating temperature in the water extraction does not influence the alcohol-soluble substances, and the improvement of the curative effect is facilitated.
5. The water extraction adopts 2 times of gradient heating extraction methods: when the temperature of the first water extraction is 100 ℃, water-soluble substances are extracted conventionally, and the adverse effect of overhigh temperature on the components is avoided; when the water extraction is carried out for the second time at 121 ℃, substances which are resistant to higher temperature and difficult to dissolve, such as long-chain polysaccharide, are beneficial to extraction, absorption and utilization.
6. The invention not only nourishes yin and subdues yang and guides qi movement to descend so as to reduce blood pressure, but also nourishes blood and liver and clears heart and calms nerves so as to promote blood pressure to be stable, form virtuous circulation and be beneficial to the recovery of blood pressure of patients with restlessness and insomnia.
Detailed Description
Example 1
2.5 parts of dendrobium officinale, 2.5 parts of fried radish seeds, 2.5 parts of radix ophiopogonis and 2.5 parts of white paeony roots:
250g of dendrobium officinale conforming to 2015 edition of Chinese pharmacopoeia, 250g of stir-fried radish seed, 250g of dwarf lilyturf tuber and 250g of white paeony root are taken. Grinding parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba into powder, adding 12 times of water, heating and extracting for 2 hr, extracting for 2 times, and concentrating to 500 g. Grinding herba Dendrobii into fine powder, adding the above parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba, extracting with water, concentrating, stirring, making into soft material, and making into pill. And (5) drying at 70 ℃. Example 1 was used. The oral dosage is 10g (or up to 30g) of crude drug per day for adult.
Example 2
10 parts of dendrobium officinale, 20 parts of fried radish seeds, 10 parts of radix ophiopogonis and 10 parts of white paeony root:
200g of dendrobium officinale conforming to 2015 edition of Chinese pharmacopoeia, 400g of stir-fried radish seed, 200g of radix ophiopogonis and 200g of white paeony root are taken. Grinding parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba into powder, adding 12 times of water, heating and extracting for 2 hr, extracting for 2 times, and concentrating to 500 g. Grinding herba Dendrobii into fine powder, adding the above parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba, extracting with water, concentrating, stirring, making into soft material, and making into pill. And (5) drying at 70 ℃. Example 2 was used. Orally administered, and the daily dose for adult is equivalent to 50g (or as small as 10g) of crude drug.
Example 3
15 parts of dendrobium officinale, 60 parts of fried radish seeds, 15 parts of radix ophiopogonis and 15 parts of white paeony root:
142.86g of dendrobium officinale conforming to 2015 edition of Chinese pharmacopoeia, 571.43g of stir-fried radish seed, 142.86g of dwarf lilyturf tuber and 142.86g of white paeony root are taken. Grinding parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba into powder, adding 12 times of water, heating and extracting for 2 hr, extracting for 2 times, and concentrating to 500 g. Grinding herba Dendrobii into fine powder, adding the above parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba, extracting with water, concentrating, stirring, making into soft material, and making into pill. And (5) drying at 70 ℃. Example 3 was used. Orally administered, and the daily dose for adult is equivalent to 105g (or as small as 10g) of crude drug.
Example 4
5 parts of dendrobium officinale, 5 parts of fried radish seeds, 5 parts of radix ophiopogonis and 5 parts of white paeony root:
250g of dendrobium officinale, 250g of fried radish seed, 250g of dwarf lilyturf tuber and 250g of white paeony root which accord with 2015 version Chinese pharmacopoeia are respectively ground, 5 times of 75 percent ethanol of the total crude drug amount is added for leaching for 24 hours at 60 ℃, the extraction is carried out for 2 times, and the residues after the ethanol extraction are extracted by water.
The water extraction adopts 2 times of gradient heating extraction methods: first water extraction: adding water 30 times of the total amount of the crude drugs, and extracting at 100 deg.C for 2 hr; and (3) second water extraction: adding water 20 times of the total amount of the crude drugs, and extracting at 121 deg.C for 2 hr. Mixing the water extracts, and concentrating.
Extracting with ethanol and water, concentrating respectively, mixing the extracts, adding appropriate adjuvant according to pharmaceutical conventional method, and making into Chinese medicinal pill. Example 4 was used. The oral administration is 20g (or up to 60g) of crude drug per day for adult.
Example 5
20 parts of dendrobium officinale, 40 parts of fried radish seeds, 20 parts of radix ophiopogonis and 20 parts of white paeony root:
200g of dendrobium officinale conforming to 2015 edition of Chinese pharmacopoeia, 400g of stir-fried radish seed, 200g of radix ophiopogonis and 200g of white paeony root are taken. Grinding respectively, adding 5 times of 75% ethanol of total crude drug amount, extracting at 60 deg.C for 24 hr for 2 times, extracting with ethanol, and extracting the residue with water.
The water extraction adopts 2 times of gradient heating extraction methods: first water extraction: adding water 30 times of the total amount of the crude drugs, and extracting at 100 deg.C for 2 hr; and (3) second water extraction: adding water 20 times of the total amount of the crude drugs, and extracting at 121 deg.C for 2 hr. Mixing the water extracts, and concentrating.
Extracting with ethanol and water, concentrating respectively, mixing the extracts, adding appropriate adjuvant according to pharmaceutical conventional method, and making into Chinese medicinal pill. Example 5 was used. Orally administered, and the daily dosage of adult is equivalent to 100g (or as small as 20g) of crude drug.
Example 6
30 parts of dendrobium officinale, 120 parts of fried radish seeds, 30 parts of radix ophiopogonis and 30 parts of white paeony roots:
142.86g of dendrobium officinale conforming to 2015 edition of Chinese pharmacopoeia, 571.43g of stir-fried radish seed, 142.86g of dwarf lilyturf tuber and 142.86g of white paeony root are taken. Grinding respectively, adding 5 times of 75% ethanol of total crude drug amount, extracting at 60 deg.C for 24 hr for 2 times, extracting with ethanol, and extracting the residue with water.
The water extraction adopts 2 times of gradient heating extraction methods: first water extraction: adding water 30 times of the total amount of the crude drugs, and extracting at 100 deg.C for 2 hr; and (3) second water extraction: adding water 20 times of the total amount of the crude drugs, and extracting at 121 deg.C for 2 hr. Mixing the water extracts, and concentrating.
Extracting with ethanol and water, concentrating respectively, mixing the extracts, adding appropriate adjuvant according to pharmaceutical conventional method, and making into Chinese medicinal pill. Example 6 was used. Orally administered, and daily dosage for adult is 210g (or as small as 20g)
Experiment 1
EXAMPLE 1 Experimental study of the antihypertensive Effect of samples on hereditary hypertension rats (SHR)
[ Experimental materials ]
Rat: 10 weeks old hereditary hypertension rats (SHR) and Wistar rats were used as normal control.
Testing the traditional Chinese medicines: example 1 test samples were dissolved with hot water immediately before use.
Western blood pressure lowering contrast medicine: irbesartan tablets (ambowei), 150 mg/tablet, batch number: 6A208, Sonofield, Inc.
Measuring the blood pressure of the rat: BP-98A type noninvasive tail artery blood pressure measuring instrument, Japan Soft fusion corporation.
[ Experimental methods ]
Grouping treatment: all rats were fed adaptively for one week and then blood pressure and body weight were measured and grouped. SHR rats are divided into a large dose group with the crude drug of 3.0g/Kg of body weight, a middle dose group with the crude drug of 2.0g/Kg of body weight and a small dose group with the crude drug of 1.0g/Kg of body weight, and are administered by intragastric administration, a hypertension model control group is infused with physiological saline with the same amount as the stomach, an irbesartan control group is infused with irbesartan with the same amount of body weight of 15mg/Kg of stomach, and a normal control group is infused with physiological saline with the same amount as the stomach. Each group had 10, 8 weeks of treatment. Blood pressure was observed for 1 week with withdrawal.
Blood pressure measurement: rats are preheated at 38 ℃ for 5-10min to avoid blood pressure measurement when the tail blood flow of the rats is low. The blood pressure value of the rat is measured 3 times continuously in a waking and resting state of the rat, and the mean value of the 3 times is taken as the blood pressure value of the rat. Blood pressure was measured 1 time at week 1 and week 2, 1 time every 2 weeks, and 2 hours after the administration.
[ Experimental results ]
Blood pressure data
Figure BDA0001323219450000073
In tables 1 and 2, the blood pressure of the large dose group is 181.7 +/-8.76/140.3 +/-6.76 mmHg, the blood pressure of the medium dose group is 192.2 +/-6.51/148.1 +/-4.79 mmHg, the blood pressure of the small dose group is 198.5 +/-6.51/152.6 +/-5.01 mmHg at 8 weeks of treatment is obviously lower than the blood pressure of the model group of 214.4 +/-8.75/164.5 +/-5.49 mmHg (P is P)<0.05). The irbesartan western medicine control group can reduce blood pressure and quickly rise after the medicine is stopped. The blood pressure reducing effect of the large-dose group is similar to the overall blood pressure reducing effect of the western medicine irbesartan control group, butAfter the medicine is stopped, the blood pressure reducing effect of a large-dose group is stable and durable.
The treatment effect is obvious in a large dose group at 1 week. From the blood pressure rising after stopping taking the medicine, the large, medium and small dosage groups are all slower than the western medicine irbesartan control group, and the traditional Chinese medicine has stable and lasting blood pressure reduction.
The rat dose used in this experiment corresponds to the equivalent adult dose:
the large dosage group corresponds to the equivalent adult dosage of about 30 g/day;
the middle dose group corresponds to the equivalent adult dose of about 20 g/day;
the small dose group corresponds to the equivalent adult dose of about 10 g/day;
the irbesartan control group corresponds to an equivalent adult dose of about irbesartan 150 mg/day.
[ conclusion ]
Example 1 samples of large dose (crude drug 3.0g/Kg body weight), medium dose (crude drug 2.0g/Kg body weight), small dose (crude drug 1.0g/Kg body weight) all had a hypotensive effect on SHR. The total blood pressure reduction effect of a large dose group (crude drug amount is 3.0g/Kg of body weight) is similar to that of irbesartan (15mg/Kg of body weight), but the blood pressure is stable and durable after the drug is stopped.
Experiment 1: TABLE 1 Effect of example 1 samples on systolic pressure in SHR rats ((S))
Figure BDA0001323219450000071
Unit: mmHg)
Figure BDA0001323219450000072
Note: Δ P <0.05 a P <0.01 compared to model group; the high dose group compared to the sartan control group □ P <0.05 ■ P < 0.01.
Experiment 1: TABLE 2 Effect of example 1 samples on the diastolic pressure in SHR rats ((S))
Figure BDA0001323219450000083
Unit: mmHg)
Figure BDA0001323219450000081
Note: Δ P <0.05 a P <0.01 compared to model group; the high dose group compared to the sartan control group □ P <0.05 ■ P < 0.01.
Experiment 2
EXAMPLE 3 Experimental study of the antihypertensive Effect of the samples of example 3 and example 6 on the genetically hypertensive rat (SHR)
[ Experimental materials ]
Rat: 18 weeks old hereditary hypertension rats (SHR), Wistar rats were used as normal control.
Testing the traditional Chinese medicines:
example 3 test samples were dissolved with hot water immediately before use.
Example 6 test samples were dissolved with hot water immediately before use.
Western blood pressure lowering contrast medicine: irbesartan tablets (ambowei), 150 mg/tablet, batch number: 6A208, Sonofield, Inc.
Measuring the blood pressure of the rat: BP-98A type noninvasive tail artery blood pressure measuring instrument, Japan Soft fusion corporation.
[ Experimental methods ]
Grouping treatment: all rats were fed adaptively for one week and then blood pressure and body weight were measured and grouped. SHR rats were divided into 21g/Kg of crude drug in the large dose group of example 6, 10.5g/Kg of crude drug in the small dose group of example 6, 10.5g/Kg of crude drug in the sample group of example 3, and 21g/Kg of crude drug in the sample (large dose) group of example 6, and administered by gavage. The gavage equivalent normal saline of the hypertension model control group, the irbesartan control group and the normal control group are respectively gavage equivalent normal saline of 15mg/Kg body weight. Each group had 10, and was treated for 2 weeks.
Blood pressure measurement: rats are preheated at 38 ℃ for 5-10min to avoid blood pressure measurement when the tail blood flow of the rats is low. The blood pressure value of the rat is measured 3 times continuously in a waking and resting state of the rat, and the mean value of the 3 times is taken as the blood pressure value of the rat. Blood pressure was measured 1 time per week and 2 hours after dosing.
[ Experimental results ]
Blood pressure data
Figure BDA0001323219450000082
As shown in tables 1 and 2, the blood pressure of the large dose group of the sample in example 6 is 169.8 + -4.86/132.1 + -7.54 mmHg, and the blood pressure of the small dose group of the sample in example 6 is 189.8 + -6.74/141.3 + -5.31 mmHg at 2 weeks of treatment, which are all significantly lower than the model group blood pressure 212.9 + -6.72/158.8 + -5.37 mmHg (P is<0.01). The blood pressure of the sample large dose group in the example 6 is lower than the blood pressure of the western irbesartan control group by 183.8 +/-5.31/138.7 +/-8.87 mmHg, and is also lower than the blood pressure of the sample control group in the example 3 by 183.7 +/-6.57/139.9 +/-5.69 mmHg.
The blood pressure of the group to which the sample (large dose) of example 6 was normally administered did not decrease, indicating that the sample of example 6 had a blood pressure lowering effect on hypertensive rats, but did not have a blood pressure lowering effect on normal blood pressure, nor was it found that the blood pressure was lowered below normal in the case of a large dose. The traditional Chinese medicine composition has the advantages of being compared with most western medicine antihypertensive medicines.
The rat dose used in this experiment corresponds to the equivalent adult dose:
example 6 the high dose group corresponds to an equivalent adult dose of about 210 g/day;
the example 6 sample low dose group corresponds to an equivalent adult dose of about 105 g/day;
example 3 the sample group corresponds to an equivalent adult dose of about 105 g/day;
the normal administration of the sample (bolus) group of example 6 corresponds to an equivalent adult dose of about 210 g/day;
the irbesartan control group corresponds to an equivalent adult dose of about irbesartan 150 mg/day.
[ conclusion ]
Example 6 the SHR is reduced in pressure by large dose (crude drug amount 21g/Kg body weight) and small dose (crude drug amount 10.5g/Kg body weight). The large dose of hypotensive amplitude was greater than irbesartan (15mg/Kg body weight).
The blood pressure reduction amplitude of the sample (crude drug amount is 10.5g/Kg body weight) in the example 3 is similar to that of the small dose (crude drug amount is 10.5g/Kg body weight) in the sample in the example 3, and is slightly larger than that of the small dose in the sample in the example 3.
The sample of example 6 had a hypotensive effect on hypertensive rats, but had no hypotensive effect on normal blood pressure, nor was it found that hypertension was reduced below normal in the case of high doses. The traditional Chinese medicine composition has the advantages of being compared with most western medicine antihypertensive medicines.
Experiment 2: TABLE 1 Effect of the samples of example 6 and example 3 on the systolic blood pressure of SHR rats ((
Figure BDA0001323219450000093
Unit: mmHg)
Figure BDA0001323219450000091
Note: Δ P <0.05 a P <0.01 compared to model group; the high dose group compared to the sartan control group □ P <0.05 ■ P < 0.01.
Experiment 2: TABLE 2 Effect of the samples of example 6 and example 3 on the diastolic pressure in SHR rats ((S))
Figure BDA0001323219450000094
Unit: mmHg)
Figure BDA0001323219450000092
Note: Δ P <0.05 a P <0.01 compared to model group; the high dose group compared to the sartan control group □ P <0.05 ■ P < 0.01.
Experiment 3
Experimental study on antihypertensive effect of genetically hypertensive rat (SHR) by combining dendrobium officinale and stir-fried radish seed
[ Experimental materials ]
Rat: the rats with hereditary hypertension (SHR) and Wistar as normal control.
Testing the traditional Chinese medicines: referring to the sample of example 3, this experimental sample was prepared:
and (3) preparing a dendrobium officinale sample: 200g of dendrobium officinale which accords with 2015 edition of Chinese pharmacopoeia is taken, ground into fine powder and dissolved in hot water before use.
Parched semen Raphani sample: taking 800g of fried radish seeds meeting 2015 edition of Chinese pharmacopoeia, grinding, adding 6 times of water, heating and extracting for 2 hours, extracting for 2 times, and concentrating to 400ml for later use.
Western blood pressure lowering contrast medicine: irbesartan tablets (ambowei), 150 mg/tablet, batch number: 6A208, Sonofield, Inc.
Measuring the blood pressure of the rat: BP-98A type noninvasive tail artery blood pressure measuring instrument, Japan Soft fusion corporation.
[ Experimental methods ]
Grouping treatment: all rats were fed adaptively for one week and then blood pressure and body weight were measured and grouped. Dividing SHR rats into 1.5g/Kg of crude drug of dendrobium officinale group, 6.0g/Kg of crude drug of fried radish seed group, 1.5g/Kg of crude drug of combined dendrobium officinale group and 6.0g/Kg of crude drug of fried radish seed group, performing intragastric administration with equal amount of normal saline solution on a hypertension model control group, performing intragastric administration with equal amount of irbesartan 15mg/Kg of irbesartan control group and performing intragastric administration with equal amount of normal saline solution on a normal control group. Each group had 10 individuals and was treated for 1 week.
Blood pressure measurement: rats are preheated at 38 ℃ for 5-10min to avoid blood pressure measurement when the tail blood flow of the rats is low. The blood pressure value of the rat is measured 3 times continuously in a waking and resting state of the rat, and the mean value of the 3 times is taken as the blood pressure value of the rat. Blood pressure was measured for 1 day, 3 days, 5 days, 7 days of treatment, 2 hours after dosing.
[ Experimental results ]
Blood pressure data
Figure BDA0001323219450000101
In the table 1 of the experiment 3 and the table 2 of the experiment 3, the blood pressure of the dendrobium officinale group is 189.1 +/-5.31/145.7 +/-4.14 mmHg, the blood pressure of the stir-fried radish seed group is 187.5 +/-5.68/146.5 +/-5.11 mmHg, the blood pressure of the combined group is 174.1 +/-4.23/132.8 +/-4.98 mmHg is obviously lower than the blood pressure of the model group which is 209.4 +/-5.91/158.8 +/-3.35 mmHg (P) in 7 days of treatment<0.05). The combined group has blood pressure lower than that of the dendrobium officinale group and the fried radish seed group (P)<0.05)。
The blood pressure reducing effect of the combined group is similar to that of the irbesartan western medicine control group.
The rat dose used in this experiment corresponds to the equivalent adult dose:
the corresponding adult dosage of the dendrobium officinale group is about 15 g/day;
the dosage of the fried radish seed group corresponding to an equivalent adult is about 60 g/day;
the corresponding adult dose of the combination group is about 15 g/day of dendrobium officinale and 75 g/day of the total crude drug of 60 g/day of stir-fried radish seeds;
the irbesartan control group corresponds to an equivalent adult dose of about irbesartan 150 mg/day.
[ conclusion ]
The combination of Dendrobium officinale (crude drug amount 1.5g/Kg weight), parched Raphani semen (crude drug amount 6.0g/Kg weight), Dendrobium officinale (crude drug amount 1.5g/Kg weight) and parched Raphani semen (crude drug amount 6.0g/Kg weight) has blood pressure lowering effect on SHR. The blood pressure reducing effect of the two medicines is obviously improved compared with that of a single medicine, and the blood pressure reducing effect of the two medicines is equivalent to that of irbesartan (15mg/Kg of body weight).
Experiment 3: TABLE 1 Effect of Dendrobium officinale and parched Raphani semen on SHR rat systolic blood pressure: (
Figure BDA0001323219450000113
Unit: mmHg)
Figure BDA0001323219450000111
Note: Δ P <0.05 a P <0.01 compared to the model group. The dendrobium officinale group and the stir-fried radish seed group are compared with the combined group in □ P <0.05 ■ P < 0.01.
Experiment 3: TABLE 2 Effect of Dendrobium officinale and parched Raphani semen on the diastolic blood pressure of SHR rats: (
Figure BDA0001323219450000114
Unit: mmHg)
Figure BDA0001323219450000112
Note: Δ P <0.05 a P <0.01 compared to the model group. The dendrobium officinale group and the stir-fried radish seed group are compared with the combined group in □ P <0.05 ■ P < 0.01.
Typical medical record
Woman, age 49, accountant. The traditional Chinese medicine composition has family history of hypertension and stroke, and the hypertension is found to be about 3 years, and western medicine hypotensor is not taken for controlling the blood pressure. Mean blood pressure 155/84mmHg in the afternoon from 2/4/2017 to 2/17/2/week, heart rate 58.2/min. The sleep time is short at night, the patient feels restless, dreams, impatience and irritability, and the stool is dry and hard.
Starting at 18 days 2 months, the samples of example 1 were taken 10 g/time, 2 times/day. Mean blood pressure 144/78mmHg in the afternoon from 2/18/3/2/week and heart rate 57.9/min. Since the traditional Chinese medicine is taken, the sleeping time is obviously increased at night, the spirit is full on the next day, the dreaminess is reduced, the mood is improved, and the stool is smooth.
[ conclusion ]
The age of the case is female climacteric age, and symptoms such as sleep reduction, vexation, dreaminess, irritability, constipation and the like are easy to appear. The blood pressure decreased after the administration of the sample of example 1, and the sleep and mood were significantly improved. Therefore, the traditional Chinese medicine conditioning is adopted for controlling the blood pressure for a long time so as to reduce various problems caused by the blood pressure reduction of western medicines.

Claims (3)

1. A method for preparing a medicine for treating hypertension by taking dendrobium officinale and radish seed as main materials is characterized by comprising the following steps:
(1) according to the requirements of 2015 version of Chinese pharmacopoeia, taking 2.5-15 parts of dendrobium officinale, 2.5-60 parts of fried radish seeds, 2.5-15 parts of radix ophiopogonis and 2.5-15 parts of radix paeoniae alba, wherein the parts are parts by weight;
(2) grinding parched Raphani semen, radix Ophiopogonis and radix Paeoniae alba respectively, mixing, extracting with hot water, and concentrating to obtain water extract concentrate;
(3) grinding herba Dendrobii into powder, and adding into the concentrated water extract; then adding auxiliary materials according to a conventional pharmaceutical processing method, and preparing into traditional Chinese medicine tablets, granules, pills or capsules to obtain the medicine for treating hypertension.
2. A method for preparing a medicine for treating hypertension by taking dendrobium officinale and radish seed as main materials is characterized by comprising the following steps:
(1) according to the requirements of 2015 version Chinese pharmacopoeia, taking 5-30 parts of dendrobium officinale, 5-120 parts of fried radish seed, 5-30 parts of radix ophiopogonis and 5-30 parts of white paeony root, wherein the parts are parts by weight;
(2) grinding the four medicinal materials into powder, and then carrying out alcohol extraction: adding 75% ethanol 5 times of the crude drug, extracting at 60 deg.C for 24 hr for 2 times, and recovering ethanol; extracting with ethanol, extracting the residue with water, concentrating, and mixing the extractive solutions;
(3) adding adjuvants according to conventional pharmaceutical processing method, and making into Chinese medicinal tablet, granule, pill or capsule to obtain medicine for treating hypertension.
3. The method of claim 2, wherein said water extraction is two gradient-heating water extractions; wherein the extraction temperature is controlled to be 100 ℃ in the first water extraction, 121 ℃ in the second water extraction, and the two extraction solutions are combined.
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