CN1706464A - A medicine for nourishing liver and kidney to treat intestinal dryness and constipation - Google Patents

Abstract

The present invention discloses one kind of medicine for invigorating liver and kidney to treat dryness of large intestine and constipation. The medicine is prepared with cynomorium 38-42 wt%, wolfberry fruit 18-22 wt%, schisandra 18-22 wt% and honey 18-22 wt%, and has sodium benzoate in 0.05 wt% added as the additive. The preparation process includes the steps of distilling schisandra to obtain distillate; soaking and twice decocting cynomorium, wolfberry fruit and the schisandra dreg, filtering, merging filtrate and concentrating to obtain paste of 1.10 density; mixing the paste with alcohol, letting stand for 24 hr, filtering, recovering alcohol, adding water, letting stand for 24 hr, filtering to obtain medicine liquid; boiling honey in water for 0.5 hr, filtering, mixing the filtrate with the medicine liquid and sodium benzoate; packing and sterilizing. The medicine is sour and sweet, and is suitable for treating dryness of large intestine, constipation and soreness of the waist and the knees.

Description

A medicine for nourishing liver and kidney to treat intestinal dryness and constipation

technical field

The invention belongs to the technical field of medicine, relates to a traditional Chinese medicine, in particular to a medicine for nourishing the liver and kidney and treating intestinal dryness and constipation.

Background technique

Constipation is the most common digestive system disease clinically. According to reports, 2 to 3 million people with constipation in the United States take medicine to help defecate every year, and the incidence rate is about 2%. A group of statistics shows that about 900 people die of constipation-related diseases every year. The main clinical manifestations of constipation are prolonged defecation intervals, dry and hard stools, or difficulty in expulsion despite intention. Constipation is essentially a functional disease of the digestive tract. Its basic pathology is the dysfunction of abdominal muscles, anal muscles, or colonic smooth muscle and myenteric plexus, which often leads to weakened defecation motivation and constipation. In treatment, laxatives are often used to increase intestinal volume to stimulate intestinal peristalsis or soften stool. The theory of traditional Chinese medicine believes that there are many causes of constipation, which are related to liver, kidney, spleen, stomach, large intestine, lung, qi, blood, body fluid, cold and heat, deficiency and excess, etc. For middle-aged and elderly people, the deficiency of liver and kidney is the main cause, and the basic pathogenesis is the basis. Deficiency and superficiality, at the beginning, the superficiality is the main one, and for a long time, the deficiency is the main one. In the treatment, it should be based on strengthening the body and consolidating the root.

The current common therapeutic drugs are stimulant laxatives, osmotic laxatives, and lubricating laxatives. The more commonly used chemical drugs include anthraquinone laxatives, salt laxatives, and vegetable oils, but long-term use produces relatively large adverse reactions. For example, long-term use of anthraquinones can cause water and electrolyte loss and colon dysfunction, and can also cause patients to become dependent on drugs. About 20% of the magnesium ions in salt laxatives can be absorbed by the intestines, and patients with renal dysfunction or central nervous system depression may have toxic reactions. Long-term use of vegetable oils can lead to the absorption of vitamins A, D, K, calcium, and phosphorus, so it is not suitable for long-term use. Commonly used traditional Chinese medicines lack recognized and effective preparations, generally have poor curative effects, and lack animal experimental studies. And this basic pathogenesis of deficiency in origin and excess in superficiality is neglected in treatment, some simply dispelling pathogenic factors (relaxing), and some simply tonify deficiency, and the effect is not ideal. Therefore, in the treatment of flaccidity and weakness of the waist and knees, intestinal dryness and constipation, there is still a lack of ideal medicines with good curative effect and little side effects.

Contents of the invention

The object of the present invention is to provide a medicine for nourishing the liver and kidneys to treat intestinal dryness and constipation. Animal experiments and drug efficacy and pharmacological tests have proved that the medicine has a good therapeutic effect on waist and knee flaccidity and intestinal dryness and constipation. .

The medicament for invigorating liver and kidney of the present invention for treating intestinal dryness and constipation contains the following traditional Chinese medicine raw materials in the weight ratio: Cynomorium cynomorium 38-42%, Lycium barbarum 18-22%, Schisandra chinensis 18-22%, honey 18-22%, Chinese medicine raw material The sum is 100%, and 0.05% of the above-mentioned traditional Chinese medicine raw material total amount of sodium benzoate is added in addition as an additive.

The preparation method of the above-mentioned medicine is as follows: the cynomorium, medlar and schisandra three medicinal materials of the formula are firstly distilled with schisandra, and 500ml of the distillate is collected for later use; another cynomorium, lycium and schisandra dregs are combined, soaked in water for 12 hours , decoct twice, the first time for 1.5 hours, the second time for 1 hour, filter in several times, combine the filtrate and concentrate at 50°C to a clear paste with a relative density of 1.10, add ethanol to make the alcohol content reach 60%-65 %, stand still for 24 hours, filter, recover the ethanol from the filtrate until there is no alcohol smell, add 2 times the amount of water, mix well, let stand for 24 hours, filter, and get the medicinal liquid; take another amount of honey in the formula, add water and boil for 30 minutes , filtered, the filtrate is mixed with the above-mentioned liquid medicine, and the additive sodium benzoate is added, water is added to the specified amount, subpackaged, and sterilized.

The medicine for invigorating liver and kidney and treating intestinal dryness and constipation prepared by the invention is a yellowish-brown liquid; the taste is sour and sweet. It has the functions of nourishing liver and kidney, nourishing essence and blood, and strengthening muscles and bones. It is especially suitable for symptoms of waist and knee flaccidity, dryness of the intestine and constipation.

Detailed ways

Below in conjunction with embodiment and drug effect, pharmacological test the present invention is described in further detail.

Example 1:

Prescription: Cynomorium 240g, medlar 120g, schisandra 120g, honey 120g, sodium benzoate 0.3g, made into 1000ml.

Preparation method: take the above three medicinal materials, distill Schisandra chinensis with water steam, collect 500ml of distillate, and set aside; take Cynomorium cynomorium, Lycium barbarum and Schisandra dregs together, soak in water for 12 hours, decoct twice, the first time 1.5 hours, the second time Second time for 1 hour, filter several times, combine the filtrate and concentrate to a clear paste with a relative density of 1.10 (50°C), add ethanol to make the alcohol content reach 60%-65%, let it stand for 24 hours, filter, and recover the filtrate Ethanol until there is no alcohol smell, add 2 times the amount of water, mix well, let stand for 24 hours, filter to obtain the liquid medicine. Take another honey, add water and boil for 30 minutes, filter, mix the filtrate with the above liquid medicine, add sodium benzoate, add water to the specified amount, subpackage, sterilize, and obtain.

Properties: yellow-brown liquid; sour, sweet.

Identification method:

(1) Take 50ml of this product, add 2g of activated carbon, stand for 10 minutes, filter, evaporate the filtrate to dryness, add 5ml of dilute ethanol to dissolve the residue, and use it as the test solution. Another Cynomorium reference drug 1g, add water 30ml, boil for 15 minutes, the same method as the reference drug solution. According to the test of thin-layer chromatography (Appendix VI B of the Chinese Pharmacopoeia in 2000), draw 5 μl of each of the above two solutions, and place them on the same silica gel G thin-layer plate with sodium carboxymethylcellulose as the binder, and place them on ice. Acetic acid-ethanol-water (4:1:2) was used as the developer, developed, taken out, dried in the air, sprayed with ninhydrin test solution, and heated at 100°C until the spots were clearly colored. In the chromatogram of the test product, there are spots of the same color at the position corresponding to the chromatogram of the control medicinal material.

(2) Take 50ml of this product, add 30ml of ethyl acetate, shake and extract, concentrate the ethyl acetate solution to 1ml, and use it as the test solution. Take 2g of wolfberry reference medicinal material, add 35ml of water, heat and boil for 15 minutes, let cool, filter, add 20ml of ethyl acetate to the filtrate and shake to extract, concentrate the ethyl acetate solution to 1ml, and use it as the reference medicinal solution. According to the test of thin-layer chromatography (Appendix VI B, Chinese Pharmacopoeia, 2000 edition), draw 5 μl of each of the above two solutions, spot them on the same silica gel G thin-layer plate, and mix with chloroform-ethyl acetate-formic acid (3:2: 1) It is a developing agent, develop it, take it out, dry it, and inspect it under a UV lamp (365nm). In the chromatogram of the test product, there are spots of the same color at the position corresponding to the chromatogram of the control medicinal material.

(3) Take 60ml of this product, add 30ml of chloroform, extract by shaking, and concentrate the chloroform solution to 1ml as the test solution. Take another 1g of Schisandra reference medicinal material, add 30ml of water, boil for 15 minutes, let cool, filter, add 20ml of chloroform to the filtrate, shake and extract, concentrate the chloroform solution to 1ml, and use it as the reference medicinal solution. According to the test of thin-layer chromatography (Appendix VI B, Chinese Pharmacopoeia, 2000 edition), draw 5 μl of each of the above two solutions, spot them on the same silica gel GF ₂₅₄ thin-layer plate, and use petroleum ether (30-60°C)-ethyl formate The upper layer solution of ester-formic acid (15:5:1) was used as the developer, developed, taken out, dried in the air, and inspected under ultraviolet light (254nm). In the chromatogram of the test product, there are spots of the same color at the position corresponding to the chromatogram of the control medicinal material.

Check item:

Relative density should not be less than 1.04 (Appendix VII A of Chinese Pharmacopoeia edition in 2000).

PH value should be 4.0～5.5 (Appendix VII G of Chinese Pharmacopoeia 2000 edition).

Others should meet the relevant provisions under the mixture item (Chinese Pharmacopoeia version one appendix IJ in 2000)

Determination of content: measure according to high performance liquid chromatography (Appendix VI D of Chinese Pharmacopoeia 2000 edition).

Chromatographic conditions and system suitability test use octadecylsilane bonded silica gel as filler; acetonitrile-water-phosphoric acid (2:98:0.2) as mobile phase; detection wavelength is 220nm. The number of theoretical plates should not be less than 2600 based on the gallic acid peak.

Preparation of Reference Substance Solution Accurately weigh an appropriate amount of gallic acid reference substance, add mobile phase to make a solution containing 2 mg per 1 ml, and obtain.

Preparation of the test solution Precisely draw 1ml of this product, put it in a 50ml measuring bottle, add mobile phase to dilute to the mark, shake well, filter, take the continued filtrate, and get final product.

Determination method Precisely draw 10 μl each of the reference substance solution and the test solution, inject it into the liquid chromatograph, measure it, and obtain it.

Specifications: Each bottle contains 10ml, and each bottle contains Cynomorium, calculated as gallic acid (C ₇ H ₆ O ₅ ), not less than 0.40mg.

Functions and Indications: Tonify liver and kidney, benefit essence and blood, strengthen muscles and bones. For flaccidity of the waist and knees, dryness of the intestines and constipation.

Usage and dosage: take orally, 10ml each time, 2-3 times a day.

Example 2:

Prescription: Cynomorium 300g, medlar 150g, schisandra 150g, honey 150g, sodium benzoate 0.375g, make a certain solution. All the other are with embodiment 1.

Example 3:

Prescription: Cynomorium 200g, medlar 100g, schisandra 100g, honey 100g, sodium benzoate 0.25g, make a certain solution. All the other are with embodiment 1.

The above-mentioned embodiments can also be exemplified in many cases, as long as the production can be scaled up within the range given by the present invention, the medicament for the purpose of the present invention can also be obtained.

Prescription analysis:

The prescription of the present invention is developed on the basis of many years of clinical research in combination with the theoretical basis of traditional Chinese medicine. In the prescription, Cynomorium is used as the monarch drug, and its function is to nourish kidney yang, benefit essence and blood, moisten the intestines and laxative, and mainly treat waist and knee weakness, intestinal dryness and constipation. Lycium barbarum has the functions of nourishing the liver and kidney, improving eyesight, and mainly treating backache and nocturnal emission due to liver and kidney deficiency. It can be used as a ministerial drug by matching Cynomorium yang to enhance the effect of nourishing the liver and kidney. Schisandra can astringe the lungs and nourish the kidneys. Its sour taste can astringe, and its nature is warm and moist. To strengthen the muscles and bones, in order to enhance the function of moistening dryness of this prescription, use honey, Ganping, moistening and nourishing to make this prescription more gentle and harmonious. The composition of this prescription is reasonable, and the combined use of various medicines achieves the effects of nourishing the liver and kidney, nourishing essence and blood, and strengthening the muscles and bones, and has significant curative effects on waist and knee flaccidity, intestinal dryness and constipation.

Cynomorium: the fleshy stem of Cynomorium Cynomorium, a fleshy parasitic herb of Cynomorium family. The property of medicine is sweet, warm. Return liver, kidney, large intestine channel. Its effect is to invigorate the kidney and yang, moisten the intestines and relieve constipation. Mainly produced in Inner Mongolia, Gansu, Qinghai, Xinjiang and other places. Harvested in spring. Remove the inflorescences, put them half-buried and half-exposed in sandy soil, and put them in the sun and scald them to make them dry and prevent mildew. Sliced raw.

1. Deficiency of kidney yang, insufficient essence and blood, impotence, infertility, flaccidity of lower limbs, weakness of muscles and bones Often used with Cistanche deserticola, velvet antler, and dodder, such as "Danxi Xinfa" Huqian pill; used for kidney deficiency, thin bones, muscles and bones Weakness and difficulty in walking, it can be used in the same way as Rehmannia glutinosa and Achyranthes bidentata.

2. Blood deficiency, body fluid deficiency, intestinal dryness and constipation can be taken alone with boiled ointment, or used with cistanche, hemp seed, and rehmannia glutinosa. For example, "Compendium of Materia Medica" treats yang weakness, essence deficiency, yin failure and blood exhaustion, dryness of the large intestine, and constipation, that is, use this product alone to decoct thick juice and add honey to collect the ointment.

Lycium barbarum: It is the mature fruit of Ningxia wolfberry of the Solanaceae plant. The property of medicine is sweet, flat. Return liver, kidney channel. The effect is to nourish the liver and kidney, benefit essence and improve eyesight. Mainly produced in Ningxia, Gansu, Xinjiang and other places. Harvest when the fruit is orange-red in summer and autumn, dry until the skin is wrinkled, and then dry until the skin is dry and hard, and the flesh is soft. It is suitable for raw use.

Liver and kidney yin deficiency and premature aging syndrome: This product can nourish the yin of the liver and kidney, and is a product for calming and tonifying kidney essence and liver blood. Treatment of vision loss, cataracts, dizziness, dizziness, soreness of waist and knees, nocturnal emission, deafness, loose teeth, premature graying of beard and hair, insomnia and dreaminess, liver and kidney yin deficiency, hot flashes and night sweats, and thirst caused by insufficient essence and blood Among the prescriptions for other certificates, they are quite commonly used. It can be used alone or in combination with products that nourish the liver and kidney, nourish essence and nourish blood. For example, "Shou Shi Bao Yuan" wolfberry paste is boiled with this product alone; Qibao Meiran Dan ("Jishantang Fang") is used together with Achyranthes bidentata, Cuscuta, Polygonum multiflorum and other products. Because it can also improve eyesight, it is especially used for liver and kidney yin deficiency or essence deficiency and blood deficiency, dry eyes, cataracts and blurred vision. It is often used together with rehmannia glutinosa, dogwood, yam, chrysanthemum, etc., such as Qiju Dihuang Wan.

Schisandra: the mature fruit of Schisandra chinensis or Schisandra sinensis. The former is commonly called "Northern Schisandra", which is mainly produced in the Northeast; the latter is commonly called "Southern Schisandra", and its medicinal properties are sour, sweet and warm. Return lung, heart kidney channel. Efficacy is astringent and astringent, nourishing qi and promoting body fluid, invigorating kidney and calming heart. It is mainly produced in the southwest and the provinces south of the Yangtze River Basin. Taken in autumn when the fruit is ripe. dry. Used raw or steamed and sun-dried with vinegar and dense mixing.

1. Chronic cough with shortness of breath This taste is sour and astringent, sweet, warm and moist. It can restrain lung qi at the top and nourish kidney yin at the bottom. It is an important medicine for treating chronic cough and shortness of breath. For chronic cough due to lung deficiency, it can be used with opium poppy shell, such as Wuweizi pill ("Healthy Jiabao Fang"); for lung and kidney deficiency, it can be used with dogwood, rehmannia glutinosa, and yam, such as Duqi pill ("Yizong" Has been edited "); this product is good at astringing the lung and relieving cough, and it is compatible with ephedra, asarum, dried ginger, etc., and can be used for cough and asthma syndrome due to cold drink, such as Xiaoqinglong Decoction ("Treatise on Febrile Diseases").

2. Spontaneous perspiration and night sweat. This product has all five flavors, mainly acid, which is good at astringing the lungs and stopping perspiration. For spontaneous sweating and night sweating, it can be used with ephedra root and oyster.

3. Nocturnal emission, spermatorrhea: This product is sweet, warm and puckery, enters the kidney, can invigorate the kidney and arrest spermatorrhea, and is a commonly used medicine for treating kidney deficiency and nocturnal emission. For the treatment of slippery essence, it can be used with mulberry octopus, aconite, keel, etc., such as mulberry octopus pills ("Shi Yi De Xiao Fang"); Wei Di Huang Wan ("Yi Zong Jin Jian").

4. Long-term diarrhea: This taste is sour and astringent, and can astringe the intestines to relieve diarrhea. To treat chronic diarrhea due to spleen and kidney deficiency and coldness, it can be fried and ground with Evodia rutaecarpa, and taken with rice soup, such as Schisandra powder ("Puji Benshifang"); or used with psoralen, nutmeg, and Evodia rutaecarpa, such as Sishen pill (Abstracts of Internal Medicine).

5. Thirst in the body fluid wound, quenching one's thirst This product is sweet to invigorate qi, acid can produce body fluid, and has the merit of invigorating qi, promoting body fluid and quenching thirst. It is often used together with ginseng and Ophiopogon japonicus to treat heat-injured qi and yin, excessive sweating and thirst, such as Shengmaisan ("Internal and Internal Injury Discrimination and Confusion"); It is used equally with yam, Anemarrhena, Tianyao powder, and astragalus, such as Yuye Decoction ("Medical Hearts in Chinese and Western Records").

6. Heart palpitations, insomnia, dreaminess This product can not only nourish the heart and kidney, but also calm the mind and nerves. Treatment of yin and blood loss, lack of nourishment of the mind, or deficiency of heart and kidney, palpitations, insomnia and dreaminess, often used with Ophiopogon japonicus, Danshen, Shengdi, Suanzaoren, etc., such as Tianwang Buxin Dan ("Health Secret Section")

Honey: Honey made by Apis mellifera or Apis mellifera. The property of medicine is sweet, flat. Return lung, spleen, large intestine channel. The function is to invigorate the middle, moisten dryness, relieve pain and detoxify. Produced in most parts of the country. Harvested from spring to autumn, filtered for use.

1. Weakness of temper, acute pain in the epigastric abdomen: This product is also a medicine for invigorating the spleen and nourishing qi rich in nutrients, suitable for those with weak temper and malnutrition. It can be taken as food. It is especially used as an excipient for Bupi Yiqi pills and ointments, or as an auxiliary material for tonifying spleen and Qi Qi. For patients with epigastric and abdominal pain due to central deficiency, abdominal pain like pressing, severe pain on an empty stomach, and slightly relieved after eating, this product can not only tonify the middle, but also relieve emergency and relieve pain, taking both symptoms and symptoms into account. Effective alone. It is more often used in combination with Paeoniae Alba, Licorice, etc. to invigorate the spleen and relieve pain.

2. Intestinal dryness and constipation This product has the effect of moistening the intestines and laxative. For those who treat intestinal dryness and constipation, it can be taken alone or mixed with rehmannia root, angelica, hemp seed, etc. Convenience product compatibility. This product can also be made into a suppository and put into the anus to guide the stool, such as honey decoction ("Treatise on Febrile Diseases").

Main Pharmacodynamic Test

Special note: The compound Cynomorium Oral Liquid that appears below all refers to the medicine for nourishing the liver and kidney of the present invention for treating intestinal dryness and constipation.

1. Defecation effect on constipated mice

1.1 Defecation test on model mice with dryness, dehydration and constipation

Take Kunming healthy mice weighing 24-26g, half male and half male, and randomly divide them into 6 groups according to body weight, namely blank control group, model control group, compound Cynomorium Oral Liquid low, medium and high dose groups and cistanche laxative oral administration liquid group. Except for the blank control group, mice in other groups were deprived of water and food for 72 hours, resulting in a model of dryness, dehydration and constipation. The blank control group was intragastrically given 2% India ink suspension configured with distilled water, and the administration group was administered intragastrically 2% Indian ink suspension that replaced distilled water with medicinal liquid, and the administration volume was 1ml/20g body weight. Finally, put the mice into the mouse box, one for each box, and put white dry filter paper under it, observe and record the time (min) of the first discharge of black feces by each mouse and the total amount of black feces discharged by the mice within 4 hours. The t test was used to test the significance of the differences among the groups, and the results are shown in Table 1.

Table 1 Effects on the defecation of dry constipation model mice with dehydration and constipation (X±S, n=10) group Dose (g/kg) Time for the first discharge of black feces (min) Points for discharging black feces within 4 hours Blank control group, model control group, low-dose group, middle-dose group, high-dose group, Cistanche laxative oral liquid 1.933.867.710.51 191.1±77.7356.1±16.9 ^ΔΔ 336.0±78.9267.1±111.1 ^* 230.3±83.2 ^** 324.6±67.9 2.4±1.70.3±0.7 ^ΔΔ 0.5±1.21.9±2.1 ^* 2.8±1.9 ^** 0.9±1.6

Note: Compared with the blank control group, ΔΔP<0.01; compared with the model control group, ^* P<0.05, ^** P<0.01

1.2 Defecation test on compound diphenoxylate (DC) model mice

Take healthy Kunming mice with a body weight of 22-24g, half male and half female, and randomly divide them into 6 groups according to body weight, blank control group, model control group, compound Cynomorium Oral Liquid low, medium and high dose groups and cistanche laxative oral liquid group . The mice in each group were deprived of water and food for 12 hours. Except the blank control group was given the same amount of distilled water, the other groups were given compound diphenoxylate (DC) suspension 50 mg/kg by intragastric administration. After 30 minutes, the animals in each group were intragastrically administered the test drug, the administration volume was 1mL/20g body weight, and the blank control group and the model control group were given the same amount of distilled water. Observe and record the number of dry feces excreted by mice in each group, the number of loose feces and the number of animals that do not defecate, observe continuously for 12 hours, compare the indicators of each group, and test the significance of the differences among the groups by t test, see Table 2.

Table 2 Effects on defecation of DC constipation model mice (X±S, n=10) group Dose (g/kg) dry manure points Loose feces points Number of non-defecating animals Blank control group Model control group Low dose group Medium dose group High dose group Cistanche laxative oral liquid group 1.933.867.710.51 8.1±4.012.5±2.43 ^ΔΔ 3.9±3.354.7±2.37 ^* 9.5±3.16 ^** 3.6±1.67 000.3±0.530.4±0.592.0±1.86 ^** 0 020000

Note: Compared with the blank control group, ΔΔP<0.01; compared with the model control group, ^* P<0.05, ^** P<0.01

The results in Tables 1 and 2 show that the high and medium doses of compound Cynomorium Oral Liquid can significantly shorten the time for the first black stool in constipated animals, and significantly increase the number of defecation points (P<0.05 or 0.01).

2. Propelling exercise test on mouse small intestine

Healthy Kunming mice with a body weight of 23-25 g, half male and half male, were randomly divided into 5 groups according to body weight, namely blank control group, low, medium and high dose groups of compound Cynomorium Oral Liquid and cistanche laxative oral liquid group. Using charcoal powder as a marker, the blank control group was given 7% carbon ink suspension prepared with normal saline, and the treatment group was given 7% carbon ink suspension prepared with medicinal liquid instead of distilled water by intragastric administration. The administration volume was 0.4mL/20g body weight, 30min after gavage; the mice were killed by cervical dislocation, and the gastrointestinal tract was taken out by laparotomy immediately, spread on a glass plate, and the moving distance of the carbon ink head in the intestinal tube and the total length of the small intestine were measured sideways (from pylorus to ileum), calculate the percentage of advancement. The t test was used to test the significance of the differences among the groups, and the results are shown in Table 3.

Table 3 Effect of Compound Cynomorium Oral Liquid on Small Intestine Propulsion in Normal Mice (X±S, n=10) group Dose (g/kg) Small intestine length (cm) Carbon ink propulsion distance (cm) Advancement percentage (%) Blank control group, low-dose group, middle-dose group, high-dose group, Cistanche laxative oral liquid group 1.933.867.710.51 51.8±3.3848.6±6.3849.5±3.7049.1±5.3348.3±4.49 39.4±3.5537.5±6.8542.9±6.3546.2±5.27 ^** 43.1±6.35 76.24±6.4877.43±9.0186.57±9.83 ^* 95.02±6.47 ^** 91.03±10.31 ^**

Compared with blank control group, ^* P<0.05, ^** P<0.01

The results in Table 3 show that the high-dose compound Cynomorium Oral Liquid group can significantly enhance the propulsive movement of the small intestine in normal animals (P<0.01).

3. Anti-stress

3.1 Cold tolerance experiment of mice: 40 ICR mice, half male and half male, were randomly divided into 4 groups, 10 mice in each group. Group A is the normal saline blank control, equal volume; Group B is the positive control of ginseng water extract, the dose is 3g/kg; Yang oral liquid high dose group, dose 7.71g/kg. 30 minutes after gavage, the mice were placed in a cold room at -5±1°C, and the time was kept while ventilation was maintained to maintain a stable concentration of oxygen and carbon dioxide in the environment. After 2 hours, the mice were taken out, the survival number of mice in each group was counted, and the survival percentage of mice in each group was calculated.

Table 4 The results of cold tolerance experiment in mice group no Dose (g/kg) number of survivors Survival rate (%) ABCD 10101010 /33.867.71 1958 1090 ^** 50 ^* 80 ^**

Compared with blank control group, ^* P<0.05, ^** P<0.01.

3.2 High temperature resistance experiment of mice: 40 ICR mice, half male and half male, were randomly divided into groups, 10 mice in each group, and the grouping and administration methods were the same as before. 30 minutes after gavage, the mice were placed in an incubator at 45±1°C, the time was recorded immediately, and the mice were closely observed to maintain ventilation and maintain stable oxygen and carbon dioxide concentrations in the environment. After 30 minutes, all the mice in the incubator were taken out, and the number of surviving mice in the administration group and the control group was calculated, and the results are shown in Table 5.

Table 5 The results of the high temperature resistance test of mice group no Dose (g/kg) number of survivors Survival rate (%) ABCD 10101010 /33.867.71 1648 1060 ^* 40 ^* 80 ^**

Compared with blank control group, ^* P<0.05, ^** P<0.01.

It can be seen from Table 4 and 5 that high doses of compound Cynomorium Oral Liquid can significantly improve the anti-stress ability of animals (P<0.05 or 0.01>.

4. Effects on male mice with "kidney yang deficiency" syndrome caused by hydrogen

Seventy-two Kunming male mice, weighing 18-22g, were randomly divided into 6 groups, administered orally or 0.5% CMCNa, once a day, for 6 consecutive days, with a volume of 20ml/kg. On the first day of the experiment, except for the intramuscular injection of normal saline in the control group, the other 4 groups were intramuscularly injected with hydrocortisone 20 mg/kg, once every other day, for a total of 3 times. One hour after the last administration, the body weight was measured and measured. Body temperature, recorded the number of spontaneous activities within 10 minutes (XZC4 small animal autonomous activity measuring instrument) and low temperature swimming (18 ℃, water depth 35cm) time, the results are shown in Table 6.

The impact of table 6 on mice "kidney yang deficiency" disease (x±s, n=12) group Dose (g/kg) body temperature (°C) Number of autonomous activities (times) Swimming time (min) Weight gain (g) Normal control model control high-dose group medium-dose group low-dose group 7.713.861.93 38.2±0.43 ^** 37.5±0.4638.2±0.45 ^** 38.1±0.57 ^* 38.1±0.50 553±93.3 ^** 327±71.7493±82.2 ^** 475±125 ^** 425±101 ^* 19.8±2.04 ^** 16.1±1.419.7±2.6 ^** 18.8±1.9 ^** 18.0±2.6 ^* 2.2±1.8 ^** -1.2±2.2-0.5±1.40.1±1.3-0.4±1.7

Compared with the model group, ^* P<0.05, ^** P<0.01.

It can be seen from the results in Table 6 that the compound Cynomorium Oral Liquid can increase the body temperature of mice with "kidney yang deficiency", increase the number of autonomous activities of mice, and prolong the time of swimming at low temperature in mice, which shows that the drug has a certain effect on mice with "kidney yang deficiency". Obvious improvement.

Toxicological Test of Compound Cynomorium Oral Liquid

1. Acute oral toxicity test in mice

Fifty healthy Kunming mice were randomly divided into 5 groups with 10 mice in each group. Five dose groups were designed according to proportional progression, the maximum dose was 62.2 g.kg ^-1 , and the adjacent dose ratio was 1:0.8. After the mice were fasted for 12 hours, they were intragastrically administered with compound Cynomorium Oral Liquid, with a capacity of 0.6ml (20g) ^-1 body weight. After exposure, they were observed for 10 days, and the symptoms of poisoning, death time and number of deaths were recorded, and Bliss Calculation of LD ₅₀ by method.

Animal poisoning after administration manifested as weakness, crawling and dyspnea until death. Within 48h, the measured LD ₅₀ was 43.34g·kg ^-1

2. Long-term toxicity test

Eighty SD rats with a body weight of 100-120 g were randomly divided into 4 groups, with 20 rats in each group, and were reared routinely. Three dosage groups of 8.7, 4.3, 2.2 g·kg ^-1 ·d ^-1 and a control group were set up with LD ₅₀ of 0.2, 0.1, and 0.05, and were administered by intragastric administration, with an administration volume of 20ml·kg ^-1 . The control group was given the same volume of distilled water. Observe for 1 week before the administration, that is, whether there is any abnormality in the animal activities, diet, and feces of each group, and then start the administration. Administered once a day on time for 45 consecutive days. During the experiment, the body weight was measured every 7 days, and the dosage was adjusted according to the change of the body weight of the rats. Record each observation index, after administration finishes and stop drug 14d, each dose group randomly takes 2/3 and 1/3 animals, carries out hematology red blood cell, hemoglobin, white blood cell count and white blood cell classification and other four routine inspections and hematology The chemical indicators (GPT, albumin, total protein, urea nitrogen, blood sugar, etc. 5 indicators) were checked, and the heart, liver, spleen, lung, kidney, uterus, testis, brain and other organs were quickly dissected and observed for abnormalities with the naked eye. Measure the weight of the above organs, calculate the organ coefficient, and conduct pathological examinations on the heart, liver, spleen, lung, kidney, rectum and other organs of the high dose and the control group.

After 3 days of administration, the stools of the rats in the high, middle and low dose groups all began to become thinner, and the low dose group improved after one week. After 30 days of administration, the anus of the high-dose group and the middle-dose group♂ became unclean and the tail was dirty, and one died on the 28th day and the 30th day of the administration period, but the above phenomenon was not seen in the control group. During the whole experiment, the body weight of the rats in each group increased in different degrees at different periods, and the body weight of the high, middle and low dose groups increased slowly during the administration period, which was significantly different from that of the control group (P<0.05). However, during the recovery period, the weight gain of rats in the high and middle dose groups was accelerated, and their physical fitness recovered well.

After the end of the administration and the recovery period, all the detection indexes (except GPT) of the rats in each group were within the normal range, and there was no significant difference between each dosage group and the control group (P>0.05, Table 1, 2) . Viscera were dissected, and no obvious lesion was seen with the naked eye. The values of each dose group and various organ indexes were close to those of the control group, and the difference had no significant significance (P>0.05). Pathological examination showed mild water degeneration in the liver tissue of some animals in the high-dose group, but the mild water degeneration in the liver tissue also disappeared during the recovery period after drug withdrawal, which was a reversible lesion, and there was no pathological change in other tissues.

In the high dose group, the daily dose was 8.7 g·kg ^-1 (equivalent to 80 times the clinical dose), which lasted for about 30 days, causing 10% of the animals to die. Rats in the high-dose group had loose stools all the time, which was caused by Cynomorium moistening intestines and defecating. At the end of the experiment, the GPT content of the high-dose group was significantly different from that of the control group (P<0.01), and the GPT value measured during the drug withdrawal recovery period was significantly lower than the GPT value measured at the end of the experiment, see Table 7. 8.

Table 7 The effect of Compound Cynomorium Oral Liquid on the blood biochemical indicators of rats by gavage for 45 days (x ± s) group GPT albumin/ Urea nitrogen/ Total protein/ blood sugar/ Control group low dose medium dose high dose Enzyme unit 18.27±4.5629.23±14.6946.96±18.2369.98±24.78 g.dl ^-1 4.36±0.274.34±0.364.26±0.663.89±0.30 g.dl ^-1 9.54±0.958.56±1.478.92±1.549.52±2.30 g.dl ^-1 8.56±0.828.22±0.808.15±0.867.98±0.77 mmol.l ^-1 2.27±0.692.31±0.522.41±0.712.26±0.77

Compared with the control group, the GPT items were all P<0.05, and the other items were all P>0.05 compared with the control group.

Table 8 The influence of rats on blood biochemical indicators after the 14d recovery period (x ± s) group GPT albumin/ Urea nitrogen/ Total protein/ blood sugar/ Control group low dose medium dose high dose Enzyme unit 20.17±4.3814.36±5.7817.66±4.2349.92±5.93 g.dl ^-1 4.26±0.314.41±0.334.41±0.5842.89±0.45 g.dl ^-1 10.52±1.199.76±1.729.33±3.128.77±2.89 g.dl ^-1 8.23±0.78.17±0.658.51±0.768.08±0.80 mmol.l ^-1 2.33±0.552.48±0.622.27±0.692.12±0.72

Except for high-dose GPT, the rest items were all P>0.05 compared with the control group.

Claims (2)

1. A medicine for invigorating the liver and kidney to treat intestinal dryness and constipation, comprising the following traditional Chinese medicine raw materials in weight ratio: Cynomorium cynomorium 38-42%, wolfberry fruit 18-22%, Schisandra chinensis 18-22%, honey 18-22%, traditional Chinese medicine raw material The total sum is 100%, and add the sodium benzoate of above-mentioned Chinese medicine raw material total amount 0.05% in addition as additive. 2. The preparation method of the medicine for invigorating liver and kidney to treat intestinal dryness and constipation, characterized in that, it is prepared according to the following steps: 1) The formula contains the following traditional Chinese medicine raw materials in weight ratio: Cynomorium 38-42%, medlar 18-22%, schisandra 18-22%, honey 18-22%, the sum of the raw materials of traditional Chinese medicine is 100%, and 0.05% of the total amount of raw materials of traditional Chinese medicine is added as an additive; 2) For the formula Cynomorium, Lycium barbarum and Schisandra chinensis, first distill Schisandra chinensis with water steam, collect 500ml of distillate, and set aside; take Cynomorium cylindrum, Lycium barbarum fruit and Schisandra chinensis dregs, add water to soak for 12 hours, decoct twice , 1.5 hours for the first time, 1 hour for the second time, filter in stages, combine the filtrates, concentrate to a clear paste with a relative density of 1.10 (50°C), add ethanol to make the alcohol content reach 60%-65%, let stand After 24 hours, filter, recover the ethanol from the filtrate until it has no alcohol smell, add 2 times the amount of water, mix well, let stand for 24 hours, filter, and obtain the medicinal solution; 3) Take another amount of honey according to the recipe, add water and boil for 30 minutes, filter, and mix the filtrate with the above-mentioned medicinal liquid; 4) Add the additive sodium benzoate, add water to the specified amount, subpackage, and sterilize.