CN100551398C - Capsule for clearing lung heat to relieve cough - Google Patents

Abstract

The invention discloses a Qingfei Zhike Capsule, which is characterized in that it is made of the following raw materials in parts by weight: 550-650 parts of Adenophora, 80-120 parts of Myrobalan, 50-80 parts of Toosendan , gardenia 80-120 parts, comfrey antler 80-120 parts, comfrey 80-120 parts, madder 80-120 parts. The medicine of the present invention is cool in nature and has the functions of clearing lung-heat and relieving cough. It is clinically used for lung heat, chest tightness, common cold and cough, hemoptysis and yellow sputum, prickly pain due to lung heat, lung sepsis, acute and chronic bronchitis, and persistent cough.

Description

Qingfei Zhike Capsules

Technical field

The invention relates to a Mongolian medicine, in particular to a Qingfeizhike capsule.

Background technique

Coughing is a defensive reflex activity produced when the respiratory system is irritated. Coughing can help remove sputum and foreign objects in the trachea, keep breathing smooth, and is beneficial to health. Generally, there is no need to take cough medicine; strong and frequent coughing is caused by a certain cause, and the aggravation of the condition may also cause complications , It is necessary to use cough medicine while treating the cause.

Contents of the invention

After repeated studies, the inventor found a Mongolian oral medicine with better curative effect for treating cough according to Mongolian medicine theory and experience, and through repeated verification of animals and clinical trials, thus completing the present invention.

The object of the present invention is to provide a Qingfeizhike capsule with remarkable efficacy in clearing lung and relieving cough.

Qingfei Zhike Capsule is a preparation composed of seven medicinal materials, including Adenophora chinensis, Myrobalan, Toosendan, Gardenia, Zicao antler, Comfrey, and Rubia. According to the theory and experience of Mongolian medicine, the prescription analysis is as follows: In the prescription, North Radix Ginseng is the main drug for clearing lung-heat. It is sweet in taste, slightly bitter, cool and soft in nature. For lung-heat cough, asthma, chest tightness, chronic bronchitis, cold and cough, etc. Myrobalan, Gardenia, and Toosendan are cool in nature, have the functions of clearing away heat and cooling blood, and separating the turbidity of bad blood and good blood. For Xinjiu blood fever, red eyes due to blood, turbidity of bad blood and good blood, plague, febrile fever, and hopeful heat. Comfrey, Zicao velvet, and madder are cool in nature, clearing lung heat, cooling blood, and relieving cough. For lung-heat cough, expectoration.

The dosage of the pharmaceutical components of the present invention is also obtained through a large amount of exploration by the inventor, and the dosage of each component has a good curative effect within the following parts by weight range:

550-650 parts of Ginseng, 80--120 parts of Myrobalan, 50--80 parts of Toosendan, 80--120 parts of Gardenia, 80--120 parts of Zicao antler, 80--120 parts of Comfrey, Madder 80--120 parts.

Preferably: 600 parts of Radix Ginseng, 100 parts of Myrobalan, 60 parts of Toosendan, 100 parts of Gardenia, 100 parts of Zicao antler, 100 parts of Comfrey, and 100 parts of Rubia.

The medicine of the present invention is made into capsules for oral administration.

The three batches of capsules were inspected under the conditions of high temperature, high humidity, light, exposure to natural light, 37-40°C and relative humidity of 75%, and regular sampling in the specified time, and the properties, identification, moisture, Disintegration time limits, assays and microbial limits are checked. The results of the preliminary stability investigation of three batches of products show that the capsule shell becomes brittle and cracked as a result of the high temperature test; the capsule shell becomes soft and the contents agglomerate as a result of the high humidity test; All indicators are in line with the relevant regulations, and the temporary validity period is two years. The long-term stability test at room temperature continues, and the final determination of the validity period is based on the observation of the reserved samples.

The medicine of the present invention is cool in nature and has the functions of clearing lung-heat and relieving cough. It is clinically used for lung heat, chest tightness, common cold and cough, hemoptysis and yellow sputum, prickly pain due to lung heat, lung sepsis, acute and chronic bronchitis, and persistent cough.

Detailed ways

The beneficial effect of the medicine of the present invention will be further elaborated below by test examples. These test examples include the pharmacodynamics test, pathology, toxicology test and clinical curative effect of the medicine of the present invention.

[Test Example 1] Pharmacodynamic study of Qingfei Zhike Capsules

The antitussive, expectorant, anti-inflammatory, immune and other effects of Qingfei Zhike Capsules were verified through animal experiments.

Test drug: Qingfei Zhike Capsule 43g/capsule (the powder in the capsule is equivalent to 2.58g/g crude drug), and the capsule is filled with brown powder.

Preparation method: Qingfei Zhike Capsules were prepared with 0.5% CMC to the required concentration before each test.

Animals: Wistar-Imamichi rats, clean (grade 2); Kunming mice, clean (grade 2), were purchased from the Experimental Animal Research Center of Inner Mongolia University.

Instrument: JSC-B Ultrasonic Atomization Therapy Apparatus (Anshan Electronic Medical Instrument Factory).

The method and results are as follows:

1. Antitussive test

50 mice, half male and half female, weighing 18-20g, were randomly divided into 5 groups, 10 mice in each group, fasted for 12hr, each group was fed Qingfei Zhike Capsules 0.32, 0.65, 1.3g/kg (approximately equivalent to crude drug 0.8, 1.7, 3.4 g/kg), the control group was given an equal volume of vehicle 0.5% CMC, and the administration volume of each group was 25 ml/kg. One hour after the administration, the mice were placed in a glass bell jar with 1000ml of solvent, and the concentrated ammonia water atomized by ultrasonic waves was sprayed into the bell jar for a total of 5 seconds. After the spraying started, the cough latency and Cough times within 2 minutes, and calculate the cough suppression rate. The results are shown in Table 1.1

Cough latency refers to the time required from the start of ammonia spray to the occurrence of cough.

Cough suppression rate (%) = [(the number of coughs in the control group - the number of coughs in the test group) ÷ the number of coughs in the control group] × 100%

Table 1.1

Group No group Dose (g/kg) Number of rats (only) Latency (seconds) Cough times (times/2min) Inhibition rate(%) 1 control group 10 22.0±3.7 58.6±14.5 2 Capsule group 0.8 10 28.5±9.0^＊ 46.8±11.0^＊＊ 20.1 3 Capsule group 1.7 10 30.9±7.9^＊＊ 34.4±8.1^＊＊ 41.3 4 Capsule group 3.4 10 32.7±9.2^＊＊ 28.9±8.5^＊＊ 50.7

Note: Compared with the control group ^* P<0.05 ^** P<0.01;

50 mice, half male and half female, weighing 18-20g, were randomly divided into 5 groups, 10 mice in each group, each group was fed Qingfei Zhike Capsules 0.32, 0.65, 1.3g/kg (approximately equivalent to crude drugs 0.8, 1.7, 3.4g/kg), the control group was given an equal volume of vehicle 0.5% CMC, and the administration volume of each group was 25ml/kg. Dosing once a day for 3 days, 1 hour after the last administration, the mice were respectively placed in jars with a volume of 500ml, injected with 5mlSO ₂ , taken out after 60 seconds, and the cough latency of each mouse was observed (by The time from the injection of SO ₂ to the occurrence of cough is the incubation period) and the number of coughs within 2 minutes, and the cough suppression rate is calculated. The results are shown in Table 1.2

Cough suppression rate (%) = [(the number of coughs in the control group - the number of coughs in the test group) ÷ the number of coughs in the control group] × 100%

Table 1.2

Group No group Dose (g/kg) Number of rats (only) Latency (seconds) Cough times (times/2min) Inhibition rate(%) 1 control group 10 25.5±6.8 48.5±14.0 2 Capsule group 0.8 10 28.4±8.4 38.0±12.1 21.6 3 Capsule group 1.7 10 31.4±10.2 33.7±10.5^＊ 30.5 4 Capsule group 3.4 10 35.0±11.4^＊ 28.9±11.2^＊ 40.4

The results showed that the middle and high dose groups could significantly reduce the number of coughs in mice induced by SO ₂ within 2 minutes, and significantly prolong the cough latency.

2. expectorant test

50 mice, half male and half female, weighing 18-20g, were randomly divided into 5 groups, 10 mice in each group, fasted for 12hr, each group was fed Qingfei Zhike Capsules 0.32, 0.65, 1.3g/kg (approximately equivalent to crude drug 0.8, 1.7, 3.4 g/kg), the control group was given an equal volume of vehicle 0.5% CMC, and the administration volume of each group was 25 ml/kg. 30 minutes after the last administration, intraperitoneally inject 5% phenol red saline solution at a dose of 500mg/kg, kill the mice 30 minutes later, separate the trachea, take a 5mm long trachea section, put it in a centrifuge tube containing 1ml of normal saline, and ultrasonically Shake for 3 minutes, centrifuge (3000r/min) for 5 minutes, transfer the supernatant to another small test tube, add 0.1ml of 1mol/L NaOH solution to make the solution alkaline, and measure the absorption value of phenol red with a spectrophotometer (A), the measurement wavelength is 546nm, and the A value is substituted into the phenol red standard curve equation to obtain the phenol red content, carry out inter-group t test, and obtain the phenol red content increase rate.

Phenol red increase rate=[(administration group phenol red content-control group phenol red content)/control group phenol red content]×100% expectorant effect is shown in Table 2.1

Table 2.1

Group No group Dose (g/kg) Number of rats (only) Phenol red output (ug/ml) Increase rate (%) 1 control group 10 2.91±0.96 2 Capsule group 0.8 10 3.87±0.88^＊ 33.2 3 Capsule group 1.7 10 4.02±0.90^＊ 38.4 4 Capsule group 3.4 10 4.24±1.08^＊＊ 46.1

Note: Compared with the control group ^* P<0.05 ^** P<0.01

50 rats, half male and half female, weighing 180-210g, were randomly divided into 5 groups, 10 rats in each group, each group was given Qingfeizhike Capsules 0.23, 0.45, 0.90g/kg (approximately equivalent to 0.6, 1.2, 2.4g/kg), the control group was given an equal volume of vehicle 0.5% CMC, and the administration volume of each group was 10ml/kg. Dosing once a day for 3 days. One hour after the last administration, 1 g/kg of urethane was intraperitoneally injected for anesthesia, and the supine position was fixed. Separate the trachea, pierce a small hole with a sharp injection needle between the two cartilages in the middle of the lower edge of the thyroid cartilage, insert a capillary glass tube so that the capillary glass tube just touches the bottom surface of the trachea, and use the capillary glass tube to absorb sputum and sputum The length is used to evaluate the expectorant effect of the drug. Observe and record the secretion amount of each mouse for 2 hours, and the results are shown in Table 2.2.

Table 2.2

Group No group Dose (g/kg) Number of rats (only) 2 hours expectoration volume (mm) 1 control group 10 14.1±3.6 2 Capsule group 0.6 10 20.9±6.2^＊＊ 3 Capsule group 1.2 10 22.1±6.0^＊＊ 4 Capsule group 2.4 10 26.1±6.7^＊＊

Note: Compared with the control group ^* P<0.05 ^** P<0.01

The results proved that Qingfei Zhike Capsules can significantly increase the amount of expectoration in rats. In addition, it can significantly prolong the cough latency of mice and reduce the number of coughs.

Conclusion: Qingfei Zhike Capsule has antitussive and expectorant effects.

3. Anti-inflammatory test

Mouse ear xylene-induced inflammation method: 50 mice, male, weighing 19-22g, were randomly divided into 5 groups, 10 in each group, each group was fed with the dose shown in Table 3, once a day, the next day After 45 minutes of administration, the right ear of each mouse was touched with a xylene cotton ball for 5 seconds. After 15 minutes, the mouse was killed by pulling the neck. Both ears were cut small. Find the ear swelling rate (swelling rate=[(inflammation ear weight-non-inflammation ear weight)/non-inflammation ear weight]×100%), compare the swelling degree difference between each administration group and the control group, the results are shown in the table 3

table 3

Group No group Dose (g/kg) Number of rats (only) Swelling rate (%) 1 control group 10 96.7±34.1 2 Capsule group 0.8 10 74.2±18.1 3 Capsule group 1.7 10 68.4±21.5^＊ 4 Capsule group 3.4 10 63.6±15.1^＊

Note: same as before; 3 groups compared with 5 groups; P>0.05

The results showed that it had obvious anti-inflammatory effect.

The influence of cotton ball granuloma hyperplasia in rats: select 50 male rats with a body weight of about 150 g, make an abdominal incision under light ether anesthesia aseptic conditions, and weigh 20 mg sterilized cotton balls (each cotton ball plus Ampicillin 1mg/0.1ml, after drying in a 50°C oven) was implanted subcutaneously in the groin on both sides of the rat. After the operation, they were randomly divided into 5 groups, 10 rats in each group, and were given 0.5% CMC and the test drug respectively, starting on the day of the operation, once a day, for 7 consecutive days. On the eighth day, the rats were decapitated, stripped and removed. Cotton ball granulation tissue was weighed after drying in an oven at 80°C for 2 hours, and the net weight of the granuloma was obtained by subtracting the weight of the original cotton ball. Compare each group's granuloma weight, and calculate inhibition rate (inhibition rate=[(experimental group granuloma net weight blank group granuloma net weight)/blank group granuloma net weight] * 100%), the results are shown in Table 4

Table 4

Group No group Dose (g/kg) Number of rats (only) Net weight of granuloma (mg) Inhibition rate(%) 1 Blank 10 255.2±40.9 2 Capsule group 0.8 10 250.6±27.1 1.8 3 Capsule group 1.7 10 228.8±33.1^＊ 10.3 4 Capsule group 3.4 10 225.3±31.3^＊ 11.7

Note: Same as before; 2 groups vs. 5 groups; P>0.05

The results show that: it has the effect of obviously inhibiting the hyperplasia of cotton ball granuloma in rats.

4. Effect on the production of mouse hemolysin antibody

50 mice, male, with a body weight of 18-22 g, were randomly divided into 5 groups, 10 in each group, and each mouse was immunized with 0.2 ml of chicken erythrocyte suspension in 5% normal saline intraperitoneally. Feeding and administration, once a day, 6 times of administration, 1.5 hours after the end of administration, decapitate, take blood, centrifuge, take serum and dilute 100 times with normal saline, take 1 ml of diluted serum, mix with 5% chicken red blood cell suspension Mix 0.5 ml, and add 0.5 ml of 1:10 diluted guinea pig serum to each tube, then transfer it to a constant temperature incubator at 37°C, keep it warm for 30 minutes, put it in an ice bath to terminate the reaction after incubation, and use 2000r/min, Centrifuge for 10 minutes, take the supernatant and compare the color at 540nm with a 721 spectrophotometer, measure the optical density (OD), and set up a blank control without serum in addition, take its supernatant as the benchmark of "0" when colorimetric, The optical density (OD) readings were used as an index to determine serum hemolysin, and the differences among the groups were compared. The results are shown in Table 5

table 5

Group No group Dose (g/kg) Number of rats (only) Optical Density (OD) 1 blank group 10 0.343±0.109 2 Capsule group 0.8 10 0.468±0.221 3 Capsule group 1.7 10 0.522±0.136^＊＊ 4 Capsule group 3.4 10 0.605±0.139^＊＊

Note: Same as before; 2 groups vs. 5 groups; P>0.05

The results show that the humoral immune function of mice can be improved.

5. Antibacterial test in vivo

Coli (4.0×10 ⁹ /ml) was successfully diluted 10 times with normal saline, and 1ml of each concentration of bacterial solution was added to 9ml of 5% peptin to make a uniform bacterial suspension. The suspension was injected into mice, 8/group, 0.5ml/mouse, the death situation was observed, and the minimum lethal dose (MLD) was found out, which was the bacterial suspension concentration that caused 80%--100% death of mice after infection.

Take 100 mice, half male and half female, weighing 18-20g, randomly divide them into 5 groups, 20 mice in each group, and give Qingfei Zhike Capsules 0.8, 1.7, 3.4g/kg respectively, and the control group is given an equal volume of solvent 0.5% CMC , once a day for 2 days. On the third day, the Escherichia coli (4.0×10 ⁶ ) suspension of MLD selected in the pre-test was used to infect mice in each group, ip0.5ml per mouse, and each group was administered once again immediately after infection, observed for 7 days, and calculated The number of dead mice was statistically processed, and the results are shown in Table 7

Table 7

The results showed that there was no obvious anti-infection effect on mice infected with Escherichia coli.

Test Conclusions:

The above results show that: Qingfei Zhike Capsule has the effects of antitussive, expectorant, anti-inflammatory, and enhancing the body's immune function. There was no obvious anti-infection effect on mice infected with Escherichia coli.

[Test Example 2] Acute Toxicity Test

The mice were fed 3 times in a day with an interval of 6 hours. They were fed and observed for 1 week. The behavior was normal and no one died. d (approximately equal to crude drug 54.2g/kg) no abnormality was found in the dissection of the surviving mice. It shows that Qingfei Zhike Capsules are non-toxic or low-toxic drugs when administered orally.

Test drug: Qingfei Zhike Capsule 0.43g/capsule (the powder in the capsule is equivalent to 2.58g/g crude drug), and the capsule is filled with reddish-brown powder.

Preparation method: Before the test, use 0.5% CMC as solvent to suspend the content of Qingfei Zhike Capsules, and prepare a suspension liquid with a concentration of 0.175g/ml (equivalent to 0.45g/ml crude drug) for intragastric administration.

Animals: Kunming white mice, 6 weeks old.

Experimental method: intragastric administration maximum tolerance determination: 20 small white mice, half male and half female, body weight 19-22g, fasted for 12 hours before administration, each time with 40ml/kg Qingfeizhike capsule suspension ( Equal to Qingfei Zhike Capsule content 7.0g/kg, approximately equal to 18.06g/kg of crude drug) orally, administered 3 times within 1 day, with an interval of 6 hours each time.

After the administration, the skin, eyes, hair, activity, feeding, breathing changes and other performances of the mice were observed, and the surviving mice were sacrificed and autopsied after 1 week.

Results: After administration, the above-mentioned observation indexes showed no abnormal reaction, and no one died after feeding and observing for 1 week (see Table 8).

Table 8

In this experiment, the maximum tolerated dose of the mice was determined to be 21.0 g/kg, and no abnormalities were found in the dissection of the surviving mice (the content of Qingfei Zhike Capsules).

Conclusion: Based on the above results, it is considered that Qingfei Zhike Capsules are non-toxic or low-toxic drugs when administered orally, and can be used clinically. From the perspective of the tolerance multiple of mice, taking 9 capsules (3.87g/day) for adults is equivalent to 325.6 times the daily dosage of adults.

Attachment: Tolerance multiple = (tolerance dose of mice/average weight of mice) ÷ (dosage for adult treatment/average weight of adults)

Intragastric administration is equivalent to the tolerated multiple of the adult oral daily dose

(0.175×0.8×3÷20)÷(0.43×3×3÷60000)＝325.6

[Test Example 3] Long-term toxicity test

Test drug: Qingfei Zhike Capsule 0.43g/capsule (the powder in the capsule is equivalent to 2.58g/g crude drug), and the capsule is filled with reddish-brown powder.

Animals and feeding: 60 8-week-old Wister-Imamichi rats, half male and half male, were purchased from the Experimental Animal Research Center of Inner Mongolia University. Rats were reared in separate cages (5 rats per cage), fed with standard block feed and tap water, and the room temperature of the animals was 18-22°C. The feed was supplied by the Experimental Animal Center of Inner Mongolia University.

Experimental method: After one week of feeding and observation, the rats were randomly divided into 3 groups according to body weight and gender, and each group had 10 male and female rats, and were given 0.5% CMC-Na (same volume as the administration group) and Qingfei Zhike Capsules by intragastric administration, respectively. 3.2, 5.8g/kg/d (respectively equivalent to crude drug 8.26, 15.0g/kg) administered once a day, 7 days a week, for 13 consecutive weeks, adjusted once a week according to animal weight. After the last administration and two weeks after drug withdrawal, 1/2 of the animals were sacrificed, and various indicators were observed. The two doses are respectively 50 and 90 times the daily clinical dose (3.87g/60kg).

Instrument: BT-2245 "ARCO" automatic biochemical analyzer made in Italy was used for biochemical determination; XQ-2 blood cell counting instrument (manufactured by Nanjing Radio Component No. 6 Factory) was used for counting red and white blood cells; TU-1221 was used for quantification of hemoglobin UV spectrophotometer.

Observation indicators: general situation: observe animal coat color, behavior, breathing, eating, activity, feces, poisoning and death every day, measure and record body weight once a week at a fixed time.

Hematological indicators: After the last administration, the rats were fasted for 12 hours, weighed again, and blood was collected from the carotid artery. Take a small amount of blood for red blood cell count (RBC), hemoglobin quantification (Hb), white blood cell count (WBC) and classification (DC), platelet count (BPC) and coagulation time (Coag time slide method), and the remaining blood is reserved as blood Determination of biochemical indicators.

Blood biochemical indicators: Take the serum from the above remaining blood and measure: aspartate aminotransferase (AST, malate dehydrogenase kinetic method), alanine aminotransferase (ALT, lactate dehydrogenase kinetic method), Alkaline phosphatase (ALP, p-nitrophenol phosphate matrix kinetics method), blood urea nitrogen (BUN, urease method), creatinine (Crea, picric acid method), total protein (TP, biuret method), blood glucose (GLU, GOP-PAP method), total cholesterol (T-CHO, CHPD-PAP method), total bilirubin (BIL, diazo method).

Pathological examination: The above-mentioned sacrificed animals were immediately subjected to pathological examination.

Systematic autopsy: All rats were dissected, and the heart, liver, spleen, lung, kidney, stomach, adrenal gland, small intestine, colon, prostate, thymus, bladder, uterus, ovary, testis, epididymis, sternum, etc. were visually observed, and heart, 11 organs including liver, spleen, lung, kidney, adrenal gland, thymus, uterus, ovary, testis, and prostate were weighed, and the organ coefficient was calculated by the ratio of organ weight to body weight (organ weight/body weight x 100%).

Histological examination: the hearts, livers, spleens, lungs, kidneys, and adrenal glands of each mouse were fixed with 10% formalin, embedded in paraffin, sectioned, stained with HE, and pathologically examined under an optical microscope and photographed.

The remaining 1/2 rats were kept alive for 2 weeks before being killed, and the above-mentioned indicators were checked in order to understand the reversibility of the toxic reaction and possible delayed toxicity.

Test Results: General Performance:

Appearance and behavior observation: During the administration period and after drug withdrawal, no abnormalities were found in the coat color, behavior, respiration, appetite, and feces of the rats in each group.

Changes in body weight: There was no significant difference in the body weights of the rats in the two medication groups compared with the blank control group (see Table 9).

The experimental results showed that Qingfei Zhike Capsules had no significant effect on the weight gain of rats.

Blood tests:

Oral administration of Qingfei Zhike Capsules for 13 weeks and withdrawal of the drug for 2 weeks showed no significant difference in the blood routine RBC, Hb, WBC, BPC, Coag time, and white blood cell classification of the rats compared with the blank control group (group between t checks). The results showed that taking Qingfeizhike Capsules orally for 13 weeks had no effect on the hematological indexes of rats. There was no statistically significant difference between each administration group and each group after 2 weeks of drug withdrawal by t-test (see Table 10).

Blood biochemical indicators:

Table 11 shows the effects of taking Qingfei Zhike Capsules orally for 13 weeks and 2 weeks after drug withdrawal on rat serum BUN, Crea, ALT, ALP, AST, TP, BIL, T-CHO and GLU. The above-mentioned biochemical indicators of the rats treated with the drug were all within the normal range, and there was no significant difference in the t test between groups, indicating that long-term oral administration of Qingfei Zhike Capsules had significant effects on liver function, kidney function and TP, BIL, T-CHO, GLU The average has no effect (although individual figures fluctuate, they are all within the normal range)

Pathological examination:

Systemic autopsy: heart, liver, spleen, lung, stomach, kidney, adrenal gland, small intestine, colon, prostate, thymus, bladder, uterus, ovary, testis and epididymis of animals in the 2 administration groups of Qingfei Zhike Capsule and the blank control group , sternum, etc., no visible changes were found in shape, size, and color. No pathological changes were found in animals after 2 weeks of drug withdrawal.

Organ coefficients: the organ coefficients of 11 important organs such as the heart, liver, spleen, lung, kidney, adrenal gland, thymus, ovary, uterus, testis and prostate of rats in each group after taking the drug for 13 weeks and after stopping the drug for 2 weeks, There was no significant difference in the t-test results among the groups in heart, liver, spleen, lung, kidney, and adrenal gland, as shown in Table 12.

No drug-induced pathological changes were found in the heart, liver, spleen, lung, kidney, adrenal gland and other tissues of the animals in the blank group and the high-dose group. There was no abnormal change in the basic structure of the pathological sections of each organ in the blank group and the high-dose group, and the telangiectasia and filling of the alveolar wall, myocardium, adrenal gland and other organs of individual rats, but there was no significant difference between the blank group and the drug-administered group . After analysis, the telangiectasia and filling of the alveolar wall and other organs may be related to the animal's struggle before execution, or the heart failure caused by blood sampling from the carotid artery. The cell morphology and structure of other organs such as heart, liver, spleen, lung, kidney, and adrenal gland were normal.

Test Conclusions:

The long-term toxicity test shows that the toxicity of Qingfei Zhike Capsules is small, and no obvious toxicity was found under the test conditions, which shows that the drug is safe under the clinical dosage conditions.

Long-term Toxicity Test of Qingfei Zhike Capsules, Pathological Anatomical Blood Observation Report

The examination specimens were the heart, liver, spleen, kidney, and adrenal gland of rats. Each organ was divided into two groups (blank and high-dose groups), and each group was divided into 13 weeks after gavage and 2 weeks after drug withdrawal. Two groups, each group has 10 slices, i.e. each organ is divided into four groups with 40 slices (10 after blank gavage for 13 weeks) and the observation results are reported as follows:

1. Liver: The observations of the four groups were basically the same. The hepatic lobule structure can be seen, the hepatocytes have clear boundaries, some polygons are round, the cytoplasm is loose, and powder stained particles can be seen in the cytoplasm, and the lobular peripheral zone, the hepatocytes are densely granulated. Individual liver cells had slight cell turbidity or vacuolar changes, and there was no significant difference among the groups.

2. Heart: The observations of the four groups were basically the same. Myocardium fibers were running normally, the striations of myocardial cells were clear, the interstitium was slightly congested, and the endocardium and epicardium were smooth without inflammation.

3. Spleen: The observations of the four groups were basically the same. The structure of the red and white pulp of the spleen was normal, the splenocytes and trabeculae were clear, and a large number of red blood cells, a small amount of macrophages, lymphocytes and multinucleated giant cells could be seen in the red pulp. No other obvious abnormal changes were found.

4. Lung: The observations of the four groups were basically the same. Alveoli, bronchioles and other structures were normal, and the alveolar cavities were of different sizes, but there was no exudate in the alveoli, and the bronchi were unobstructed without inflammation, and no obvious abnormal differences were found. Individual lung tissue sections showed local non-bubble telangiectasias and hyperemia, and there was no significant difference among the groups.

5. Kidney: The observations of the four groups were basically the same. There were no obvious abnormal changes in glomeruli and renal tubules. The size of the glomeruli was uniform, the proximal convoluted tubules were powder-stained with cytoplasm, without granules, and the nuclei were uniform in size and arranged neatly. Individual renal tissue cells were slightly turbid and swollen, and there was no significant difference among the groups.

6. Adrenal gland: The observations of the four groups were basically the same. The structure of adrenal cortex and marrow was normal, and no obvious abnormal changes were found.

From the observations of the above organs, no swelling and toxic changes such as deformation and necrosis of parenchymal cells were seen, and the observations between the blank control group and the high-dose group were basically consistent. After analysis, we believe that the turbidity and swelling of some cells in the liver and kidney tissue may be due to the lack of timely collection of specimens or too large specimens after the animals were sacrificed, and failure to fix them in time. The cells are hypoxic, and the capillaries in the alveolar wall are dilated and congested, which may be related to the animals. It is related to the struggle before death, not to taking drugs.

No specific lesions caused by the drug were found in the above organs of all experimental animals.

The medicine of the present invention is further described below by way of examples.

[Example 1]

A Qingfeizhike capsule, which is composed of 600g of ginseng, 100g of myrobalan, 60g of toosendan, 100g of gardenia, 100g of antler, 100g of comfrey and 100g of madder.

[Example 2]

A capsule for clearing lung and relieving cough, which is composed of 550g of ginseng, 80g of chebula, 50g of toosendan, 80g of gardenia, 80g of antler, 80g of comfrey and 80g of madder.

[Example 3]

A capsule for clearing lung and relieving cough, which is composed of 650g of ginseng, 120g of chebula, 80g of toosendan, 120g of gardenia, 120g of antler, 120g of comfrey and 120g of madder.

对大鼠体重(g)的影响(X±SD)surface

Effect on rat body weight (g) (X±SD)

Note: *P<0.05; **P<0.01 (n=10, n=5 from week 14)

Claims (2)

1, a kind of capsule for clearing lung heat to relieve cough is characterized in that: made by following bulk drugs: Radix Glehniae 550-650 part, Fructus Chebulae 80--120 part, Fructus Toosendan 50--80 part, Fructus Gardeniae 80--120 part, Lacca 80--120 part, Radix Arnebiae (Radix Lithospermi) 80--120 part, Radix Rubiae 80--120 part are formed.

2, capsule for clearing lung heat to relieve cough according to claim 1 is characterized in that: wherein the consumption of each crude drug is: 600 parts of Radix Glehniaes, 100 parts of Fructus Chebulaes, 60 parts of Fructus Toosendans, 100 parts of Fructus Gardeniaes, 100 parts of Laccas, 100 parts of Radix Arnebiae (Radix Lithospermi)s, 100 parts in Radix Rubiae.