CN100435817C - A Chinese medicinal composition for treating respiratory system diseases, and its preparation method - Google Patents

Abstract

The invention discloses a Chinese medicine composition for treating respiratory diseases, wherein the raw materials are ephedra (fried with honey), gypsum, bitter almond (fried), mulberry bark (fried with honey), scutellaria baicalensis (fried), angelica, salvia miltiorrhiza, earthworm, bombyx batryticatus (fried), and liquorice. Also disclosed are the antiviral, antibacterial, antipyretic, antitussive, expectorant, antiasthmatic and anti-inflammatory applications of the Chinese medicine preparation, as well as its preparation method and detection method of active ingredients. The composition is a Chinese medicine with the main effects of clearing the lungs and resolving phlegm, relieving cough and relieving asthma, and promoting blood circulation and removing blood stasis, and is mainly used to treat phlegm-heat cough syndrome in the recovery period of acute bronchitis or pneumonia, and is particularly suitable for children.

Description

A traditional Chinese medicine composition for treating respiratory diseases and its preparation method

technical field

The invention relates to a traditional Chinese medicine composition, in particular to a traditional Chinese medicine composition for treating respiratory diseases, and a preparation method thereof.

Background technique

Acute bronchitis is one of the most common frequently-occurring diseases in respiratory diseases, especially children are susceptible groups. According to statistics, the disease accounts for about 9% to 11% of children's diseases. Due to improper treatment, the disease is prolonged and recurrent, which can seriously affect the health and development of children's bodies. At present, there are many treatment methods for this disease. Both western medicine and traditional Chinese medicine have certain curative effects, but there are deficiencies, such as the use of antibiotics for too long, which can produce drug-resistant strains, especially can lead to flora disorder, digestive bad. Moreover, more than 90% of current respiratory diseases are mainly caused by viral infections, and there is a trend of abusing antibiotics at present, resulting in an excessive burden of treatment costs, while traditional Chinese medicine has certain advantages in treating viral infections.

At present, the varieties recorded in the Chinese Pharmacopoeia (2005 edition) and sold on the market with similar functions and indications include "Children Feire Kechuan Oral Liquid", "Xiaoer Kechuan Granules" and Jizhi Syrup (Granules), etc. Due to the different composition, pertinence and emphases of each party, the curative effects produced are also different. The Chinese patent medicines currently available on the market to treat such diseases (especially suitable for children) include Xiaoer Feire Kechuan Oral Liquid and Xiaoer Kechuan Granules, which are additions and subtractions of the ancient prescription Maxing Shigan Decoction, but in There is no breakthrough in thinking; Jizhi syrup (granules) (which can also be used in children) is a prescription formed on the basis of modern pharmacology, but lacks the overall concept of traditional Chinese medicine.

Contents of the invention

The present invention overcomes the deficiencies of the above-mentioned prior art, and is a bold innovation based on the theory of traditional Chinese medicine, especially a traditional Chinese medicine prescription that introduces the concept of promoting blood circulation and removing blood stasis and dredging airway into the treatment plan of this disease.

The purpose of the present invention is to provide a new traditional Chinese medicine composition for treating respiratory diseases.

Another object of the present invention is to provide a preparation method for preparing the above-mentioned traditional Chinese medicine composition.

Another object of the present invention is to provide the application of the above-mentioned traditional Chinese medicine composition.

Another object of the present invention is to provide a method for testing the active ingredients of the above-mentioned traditional Chinese medicine composition.

After many years of research, repeated scrutiny and long-term clinical practice, the inventor has designed a Chinese medicine composition for treating respiratory diseases. Yan belongs to the pathogenic characteristics of phlegm-heat cough syndrome and has been developed in clinical records, so this prescription has dual basis of ancient prescriptions and practical experience. The composition is used for treating acute bronchitis with phlegm-heat cough syndrome (especially in children), and has the characteristics of quick effect, short course of treatment, less adverse reactions, etc., and also has good curative effect on phlegm-heat cough syndrome in recovery period of pneumonia. Its raw material medicine consists of (based on 1000g finished product):

Ephedra (honey roasted) 75-175g

Gypsum 750-1750g

Bitter almonds (fried) 75-175g

Mulberry bark (honey roasted) 75-175g

Tinglizi (fried) 30-120g

Angelica 125-250g

Danshen 125-250g

Earth Dragon 75-175g

Silkworm (fried) 75-175g

Licorice 75-175g

The preferred raw material composition is:

Ephedra (honey roasted) 100-150g

Gypsum 1000-1500g

Bitter almonds (fried) 100-150g

Mulberry bark (honey roasted) 100-150g

Tinglizi (fried) 50-100g

Angelica 150-226g

Danshen 150-226g

Earth Dragon 100-150g

Silkworm (fried) 100-150g

Licorice 100-150g

A particularly preferred bulk drug consists of:

Ephedra (honey roasted) 112-137g

Gypsum 112-1370g

Bitter almonds (fried) 112-137g

Mulberry bark (honey roasted) 112-137g

Tinglizi (fried) 68-82g

Angelica 170-206g

Danshen 170-26g

Earth Dragon 112-137g

Silkworm (fried) 112-137g

Licorice 112-137g

The most preferred bulk drug consists of:

Ephedra (honey roasted) 125g

Gypsum 1250g

Bitter almonds (fried) 125g

Mulberry bark (honey roasted) 125g

Tinglizi (fried) 75g

Angelica 188g

Danshen 188g

Dilong 125g

Silkworm (fried) 125g

Licorice 125g

Acute bronchitis belongs to the category of "cough" in traditional Chinese medicine, its pathological mechanism is related to phlegm, and the pathological site is in the lungs. Traditional Chinese medicine believes that: "The lungs govern qi, close the skin and hair outside, open into the nose, and function to breathe and regulate waterways. In addition, cold and warm cannot be adjusted by themselves, so the evils of the six evils can enter the human body through the mouth, nose or fur, resulting in blocked hair orifices, loss of ventilation and descending of the lungs, and symptoms such as colds, coughing, phlegm, and wheezing. The body of yang, the yang is always surplus, and the yin is often insufficient. Feeling external pathogens tends to turn into heat and injure the lungs. The body fluid of the lungs is burned into phlegm. If the lung qi is reversed upward, hot phlegm will block the airway, and phlegm will sound in the throat; and because qi is the commander of blood, qi circulates and blood circulates, and stagnation of qi leads to blood stasis. If the phlegm heat does not condense, it can lead to the endogenous pathogenesis of blood stasis. The characteristic of this prescription is to clear the phlegm and heat, dredge the airway a little bit, promote blood circulation and remove blood stasis, and it has repeatedly obtained good results. It has been clinically proven to have a remarkable curative effect. Because the heat clears phlegm, and the lung qi is smooth, all the symptoms of cough and asthma can be cured quickly.

This prescription uses ephedra and raw gypsum as monarch drugs. Ephedra, pungent in nature and flavor, bitter, warm. Pungent can dissipate, bitter can reduce, and warm can be relieved, so it can produce sweat, relieve asthma and diuresis. After honey-burning, the sweating effect is weakened, whichever is the effect of relieving asthma and relieving cough. Raw gypsum, spicy, sweet, great cold. Clearing away heat and purging fire, relieving restlessness and quenching thirst. Mainly used for lung and stomach qi, excess heat syndrome, cough and asthma due to lung heat. Spicy, sweet, and cold in taste but not dry in texture, it has a strong effect of clearing heat and purging fire, and can clear away internal heat and disperse it thoroughly. It is most suitable for fever, cough, and asthma caused by heat stagnation and lung failure. The combination of the two medicines has the effects of clearing away heat and venting the lungs, relieving cough and relieving asthma, relieving restlessness and relieving cough, and it is used as the monarch drug in the prescription.

Bitter almond, Morus alba, and Tinglizi are ministerial medicines altogether. Bitter almond, bitter and slightly warm, slightly poisonous, relieves cough and asthma. "Treatise on Febrile Diseases" Mahuang Xingren Shigao Gancao Decoction is the main prescription for treating cough and asthma due to lung heat, congested heat in the lungs, loss of lung qi, and cough, asthma, and thirst. This prescription is based on the above, and it is flavored according to the phlegm-heat cough syndrome. Among them, Morus alba is sweet and cold in nature and taste, and it can relieve lung and relieve asthma. There is an ancient saying that "if the lungs are more than purged, it must be the mulberry bark". Tinglizi, hard work and severe cold. Expelling lung and relieving asthma, inducing diuresis to reduce swelling, divides medicine for lung family qi. It is suitable for those with excessive phlegm and saliva, who are unable to sleep due to cough, asthma and chest tightness. Bitter almond, Morus alba, and Tinglizi are three medicines together, and they are ministerial medicines. The emperor medicine ephedra and raw gypsum are used to clear away heat and relieve lungs, relieve cough and relieve asthma.

In the prescription, angelica, salvia, earthworm, and silkworm are adjuvant drugs. Angelica, sweet and pungent tonify blood and regulate menstruation, promote blood circulation and relieve pain, are their conventional usages. The "Ben Jing" claims that it can "maintain cough and upper qi". The sages used angelica for cough and asthma, and it was mostly used together with expectorant, cough and asthma medicine, such as Suzi Jiangqi Decoction and Jinshui Liujun Decoction. Salvia Miltiorrhiza, bitter and slightly cold, promotes blood circulation and removes blood stasis, cools blood and eliminates carbuncle, relieves restlessness and calms the nerves. The combination of the two medicines has the function of promoting blood circulation and removing blood stasis, eliminating phlegm and relieving cough, so that phlegm-heat stagnation can be activated and dissipated. Earthworm, salty and cold, clearing heat and relieving asthma; Bombyx mori, Xianxinping, dispelling wind and relieving spasm, resolving phlegm and resolving stagnation. The two medicines work together to clear away heat and relieve spasm, relieve asthma, resolve phlegm and dissipate stagnation, make the airway comfortable, phlegm turbidity is easy to cough up, and the bitterness of cough and asthma disappears immediately. Bombyx mori and Earthworm both have the effects of relieving wind and convulsions, resolving phlegm and dispelling stagnation, and relieving asthma and expelling heat. "Compendium of Materia Medica" says: "White silkworm, pungent in taste, warm in temperature and dry in nature, so it is used to treat wind and phlegm that dampness prevails,...the silkworm robs phlegm and dampness and dissipates liver wind, so it is the main treatment." Modern pharmacology has also It has been confirmed that silkworm has hypnotic and anticonvulsant effects; earthworm has antipyretic, sedative and antiasthmatic effects, and modern pharmacology has also shown that it has a significant bronchial dilation effect, which can expand bronchial smooth muscle to achieve airway comfort and calmness. The purpose of asthma is to alleviate and treat acute bronchitis with phlegm-heat obstructing the lung syndrome, which strengthens the effects of expectorant, asthma and sedation. The composition of the invention makes the compatibility of the prescription more rigorous and thorough by adding the two herbs of the silkworm and the earthworm, and thus obtains satisfactory clinical effects. On the basis of the above-mentioned medicinal flavors, the above four herbs, especially the last two herbs, are often effective, and at the same time, they can prevent or treat endogenous blood stasis and convulsions caused by phlegm and asthma in children. The licorice in the prescription is used as the medicine, and its nature and taste are sweet and flat. There are heat-clearing and toxic substances removing, eliminating phlegm and relieving cough, relieving asthma, with the merit of promoting blood circulation and resolving phlegm.

This prescription is mainly used to clear away heat and relieve lung heat, and can promote blood circulation and remove blood stasis, so that phlegm and blood stasis can be dissipated, and the airway can be more comfortable. All the syndromes of stagnant lung are eliminated. This prescription treats both the symptoms and the root causes, mainly treating the symptoms. The prescription is mainly based on Zhongjing Mahuang Xingren Shigao Gancao Decoction, and the product of clearing diarrhea, removing blood stasis, dispelling wind and relieving spasm is really a characteristic of this prescription.

The preparation method of Chinese medicine composition of the present invention can adopt the conventional preparation method of Chinese patent medicine preparation, and wherein the leaching method of Chinese medicine composition can refer to the second chapter of " Pharmacy " (third edition) edited by Xi Mianzhu (People's Health Publishing House, 1996 Year), and adopt the preparation method of conventional preparation to prepare this traditional Chinese medicine composition into dosage forms such as granule, capsule, tablet, oral liquid and ointment.

The preparation method of the Chinese medicine composition can be: weighing the above ten raw materials, adding 20 to 3 times of water, preferably 10 to 4 times; decocting 1 to 4 times, preferably 2 to 3 times; each time for 0.5 to 4 hours, Preferably, within 0.5-2 hours, the decoctions are combined, filtered, the filtrate is allowed to stand, and the supernatant is concentrated under reduced pressure to a clear paste with a relative density of 1.0-1.3 (50-80°C). Add corresponding auxiliary materials according to the requirements of the preparation dosage form, for example, to prepare granules, add an appropriate amount of citric acid to the obtained clear paste, dissolve, mix well, then add sucrose powder or other auxiliary materials and an appropriate amount of ethanol, which is 1 to 5 times the amount of dry paste, Granulate and subpackage to obtain granules; for example, to prepare oral liquid, add appropriate amount of honey and preservative sodium benzoate to the concentrated supernatant, boil to dissolve, add appropriate amount of water, stir well, refrigerate for 24-48 hours, filter Pouring, sealing, and sterilizing, the oral liquid is obtained; for example, to prepare capsules, put the obtained clear paste in cold, add ethanol to make the alcohol content reach more than 65%, stir well, let stand for more than 24 hours, filter, and recover the filtrate Concentrate ethanol to a relative density above 1.0 (about 70°C), add dextrin 2.5 times the amount of dry paste, spray dry to obtain powder, and then carry out one-step granulation, and encapsulate the obtained granules to obtain capsules; for example, preparing Tablets, let the obtained clear paste cool, add ethanol to make the alcohol content reach more than 65%, stir well, let it stand for more than 24 hours, filter, recover ethanol from the filtrate and concentrate to a relative density of more than 1.0 (about 70°C) , add 2 times the amount of pregelatinized starch to dry paste, spray dry to obtain powder, and then carry out one-step granulation, granulation, tablet compression or film coating or sugar coating to obtain tablets.

It should be pointed out that for those skilled in the art, when preparing various dosage forms of the traditional Chinese medicine composition of the present invention, it is possible to add other adjuvants or reduce adjuvants, or improve the process. The means commonly used in formulation technology are still within the scope of the present invention.

Active substance testing method in the Chinese medicine composition of the present invention is:

Identification method

(1) Get 10g of the composition of the present invention, grind it finely, add 2ml of concentrated ammonia test solution, add 30ml of chloroform, heat and reflux for 1 hour, let it cool, filter, evaporate the filtrate to dryness, add 1ml of methanol to the residue to dissolve it, and use it as a sample for testing product solution. Take another ephedrine hydrochloride reference substance, add methanol 1ml to make a solution containing 1mg per 1ml, as the reference substance solution. Test according to thin-layer chromatography (Appendix VIB of Chinese Pharmacopoeia in 2000), draw each 2-5ul of the above two solutions, and place them on the same silica gel G thin-layer plate respectively, and use chloroform-methanol-concentrated ammonia test solution (20: 5:0.5) as the developer, develop, take out, dry in the air, spray with 0.2% ninhydrin ethanol test solution, and bake at 105°C for about 5 minutes. In the chromatogram of the test product, the same red spot appears at the position corresponding to the chromatogram of the reference product.

(2) Take 10 g of the composition of the present invention, grind it finely, add 20 ml of ethanol, treat it with ultrasound for 20 minutes, let it cool, filter, evaporate the filtrate to dryness, add 2 ml of ethanol to the residue to dissolve, and use it as the test solution. Take another 1 g of licorice reference medicinal material, and make a reference medicinal material solution in the same way, test according to thin-layer chromatography (Appendix VIB, Chinese Pharmacopoeia, 2000 edition), absorb 5 ul of the test solution, and 1-3 ul of the reference medicinal material solution, and place them on the same silica gel respectively. On G thin-layer board, develop with toluene-ethyl acetate-glacial acetic acid (10:10:0.5) as a developer, take it out to dry, spray with 10% sulfuric acid ethanol solution, bake at 105°C for about 5 minutes, and put it under ultraviolet light. View under light (365nm). In the chromatogram of the test product, at the position corresponding to the chromatogram of the control medicinal material, the same blue-purple fluorescent main spot appears.

(3) Take 10 g of the composition of the present invention and grind it finely, add 30 ml of methanol, sonicate for 20 minutes, filter, evaporate the filtrate to dryness, dissolve the residue in 15 ml of 1% ammonia solution, combine, extract 2 times with chloroform, each 20 ml , Discard the chloroform solution, take the alkali solution and add 2ml of dilute hydrochloric acid, mix well, extract 2 times with ether, 20ml each time, combine the ether solution, evaporate to dryness, add 1ml of methanol to the residue to dissolve, and use it as the test solution. Take another ferulic acid reference substance, add methanol to make a solution containing 1mg per 1ml, as the reference substance solution. Test according to thin-layer chromatography (Chinese Pharmacopoeia, an appendix VIB of edition in 2000), draw need testing solution 5-10ul, reference substance solution 5ul, point respectively on the same silica gel G thin-layer plate, with benzene-methanol-glacial acetic acid ( 30:3:1) as the developing agent, develop, take out, dry in the air, and smoke in iodine vapor for several minutes until the spots are clearly colored. spot.

(4) Take 1 g of Danshen reference medicinal material, add 30 ml of water and decoct for 30 minutes, let cool, filter, add 2 ml of dilute hydrochloric acid to the filtrate, extract twice with ether, 20 ml each time, combine the ether solution, evaporate to dryness, add 1 ml of methanol to the residue to make Dissolved as a reference medicinal solution. Test according to thin-layer chromatography (Chinese Pharmacopoeia, one appendix VI B of edition in 1995), draw and identify (3) under need testing solution 5ul, reference substance solution 2ul, point respectively on the same silica gel G thin-layer plate, with benzene- Ethyl acetate-formic acid (4:1:0.2) was used as the developer, developed, taken out, dried in the air, and inspected under a UV lamp (365nm). In the chromatogram of the test product, at the position corresponding to the chromatogram of the control medicinal material, fluorescent spots of the same color should appear.

Content determination (ephedra):

Determination method 1 Preparation of reference substance solution Accurately weigh an appropriate amount of ephedrine hydrochloride reference substance, add water to make a solution containing 0.02mg per 1ml, and obtain it.

The preparation of need testing solution takes an appropriate amount of the composition of the present invention, carries out steam distillation after adding sodium chloride and 40% sodium hydroxide solution, and distillate puts in the measuring bottle containing dilute hydrochloric acid, adjusts with 40% sodium hydroxide solution pH value to 6.0-7.0 to make the test solution.

Determination method Take the above two solutions and add the citric acid-disodium hydrogen phosphate buffer containing bromothymol blue respectively, then add chloroform for extraction, separate the chloroform layer, and measure the absorbance at 414nm wavelength by spectrophotometry , calculate and get. Concrete content is: each 3ml of above-mentioned two kinds of solutions is drawn carefully, puts respectively in the Erlenmeyer flask with stopper, each precisely adds 10ml of citric acid-disodium hydrogen phosphate buffer solution (pH7.6) containing 0.0125% bromothymol blue, After shaking well, add 10ml of chloroform each precisely, shake fully for 3 minutes, pour into a separatory funnel, shake gently, and stand still for 10 minutes, separate the chloroform layer, stand still for 5 minutes, use the corresponding reagent as a blank, and take the spectroscopic Photometric method (Appendix VB of Chinese Pharmacopoeia 2000 edition) test, measure absorbance at 414nm wavelength place, calculate promptly.

Determination method 2 Preparation of control solution Dilute ephedrine hydrochloride with water, add appropriate amount of periodate and sodium hydroxide solution, adjust pH to 7 with hydrochloric acid, and add appropriate amount of methanol to prepare reference solution.

Preparation of the test solution Take an appropriate amount of this product, add an appropriate amount of sodium hydroxide solution, shake well, add an appropriate amount of sodium chloride, and ultrasonically distill and extract it into a measuring bottle filled with hydrochloric acid solution in advance, take an appropriate amount of dilution, and then add periodic acid Add an appropriate amount of sodium hydroxide solution, adjust the pH to 7 with hydrochloric acid, add an appropriate amount of methanol to dissolve and filter, and then take the subsequent filtrate.

Determination method Take the above two solutions and inject them respectively into a liquid chromatograph with octadecylsilane bonded silica gel as a filler, and use methanol-water (1:1) as a mobile phase; the detection wavelength is 254nm, and the number of theoretical plates Calculated by ephedrine hydrochloride should not be less than 3000.

Calculated by the above two methods, every 1 g of the composition of the present invention contains ephedra, calculated as ephedrine hydrochloride (C ₁₀ H ₁₅ NO·HCL), not less than 0.30 mg.

Animal experiments prove that the composition of the invention has antiviral, antibacterial, antipyretic, antitussive, expectorant, asthmatic and anti-inflammatory effects.

Clinical trials show that the composition of the present invention is superior to "Jizhi Granules" commonly used in clinical practice for children with acute bronchitis and phlegm-heat cough, and can significantly improve clinical symptoms and signs. It has the characteristics of short course of treatment, quick effect, stable dosage form, and no obvious side effects. Therefore, the composition of the present invention can be used for treating acute bronchitis or pneumonia with phlegm-heat cough syndrome, especially suitable for children.

The composition of the present invention is administered orally. Taking the mixture as an example, 10ml once from the age of one to three, 15ml once from the age of three to seven, 20ml once from the age of seven to twelve, and 20ml once from the age of twelve to ten. 30ml once at the age of four, 40ml once at the age of fourteen, three times a day; or follow the doctor's advice. Other dosage forms can be taken with reference to the dosage of the oral liquid (converted by the content of active ingredients).

Description of drawings

Figure 1 shows normal mouse lung tissue (×200)

Figure 2 shows that the small blood vessels in the alveolar wall are slightly dilated (×100)

Figure 3 shows that the small blood vessels in the alveolar wall are obviously dilated and congested (×100)

Figure 4 shows that the small blood vessels in the alveolar wall are dilated and congested, accompanied by focal hemorrhage (×100)

Fig. 5 represents the heat-clearing effect of preparation of the present invention

Detailed ways

Embodiments of the present invention are specifically described below through examples, and those skilled in the art should recognize that these specific examples only show the technical solutions selected for implementation in order to achieve the purpose of the present invention, but are not limitations on technical solutions It is obvious to improve the technical solution of the present invention according to the prior art, and all belong to the protection scope of the present invention.

Example 1

API

Ephedra (honey roasted) 125g Gypsum 1250g Bitter almond (fried) 125g

Mulberry bark (honey roasted) 125g Tinglizi (fried) 75g Angelica 188g

Danshen 188g Dilong 125g Bombyx silkworm (fried) 125g

Licorice 125g

Preparation method: add 6.5 times of water to decoct the above ten flavors three times, each time for 1.5 hours, combine the decoction, filter, let the filtrate stand still, take the supernatant and concentrate under reduced pressure to a relative density of 1.2-1.25 (50°C) Clear paste, add 2.5g of citric acid, dissolve, mix evenly, then add sucrose powder (2.99 times the amount of dry paste) and an appropriate amount of ethanol, granulate, and make 1000g of granule I-A of the present invention, namely 250 bags or 25 bottles (4g/bag per bag, or 40g per bottle).

According to the above-mentioned detection method of active ingredients, it is measured that every 1 g of ephedra contains ephedrine hydrochloride (C ₁₀ H ₁₅ NO·HCL), which is greater than 0.60 mg.

Example 2

With reference to Example 1, the difference is: add 8 times of water and decoct twice, each time for 2 hours. Prepare the granule I-B of the present invention.

Example 3

Ephedra (honey roasted) 175g Gypsum 750g Bitter almond (fried) 175g

Mulberry bark (honey roasted) 75g Tinglizi (fried) 120g Angelica 125g

Danshen 250g Dilong 75g Bombyx silkworm (fried) 175g

Licorice 75g

Take the above ten raw materials, add 8 times of water and decoct 2 to 3 times, 2 hours each time, combine the decoction, filter, and filtrate, the filtrate is concentrated under reduced pressure to a relative density of 1.1-1.2 (50°C), add appropriate amount Honey and 0.2% sodium benzoate are boiled to dissolve, add an appropriate amount of water, stir well, refrigerate for 24 to 48 hours, filter, seal, and sterilize to obtain 100 bottles (10ml per bottle) of oral liquid preparation II-A of the present invention .

Example 4

Referring to Example 3, the difference is: add 6 times of water and decoct 2 to 3 times, each time for 1 hour. The oral liquid preparation II-B of the present invention is obtained.

Implementation Example 5

Ephedra (honey roasted) 150g Gypsum 1500g

Bitter almond (fried) 150g Morus almond (honey roasted) 150g

Tinglizi (fried) 100g Angelica 226g

Danshen 226g Earthworm 150g

Silkworm (fried) 150g Licorice 150g

Weigh the above ten raw materials, add 12 times of water and decoct twice, 2 hours each time, combine the decoction, filter, concentrate the filtrate to a clear paste with a relative density of 1.1-1.25 (80°C), let it cool, and add ethanol Make the alcohol content reach more than 65%, stir evenly, let it stand for more than 24 hours, filter, recover ethanol from the filtrate and concentrate to a relative density of more than 1.0 (about 70°C), add dextrin with 2.5 times the dry paste amount, and spray dry After obtaining the powder, carry out one-step granulation again, will make granule pack capsule and promptly obtain 3000 capsule preparations III-A of the present invention.

Example 6

Referring to Example 5, the difference is: add 10 times of water and decoct 3 times, each time for 2 hours. The capsule preparation III-B of the present invention is obtained.

Example 7

Ephedra (honey roasted) 137g Gypsum 1370g

Bitter almond (fried) 137g Morus almond (honey roasted) 137g

Tinglizi (fried) 82g Angelica 206g

Danshen 206g Earthworm 137g

Silkworm (fried) 137g Licorice 137g

Weigh the above ten raw materials, add 10 times of water, decoct 2 to 3 times, 1 to 2 hours each time, combine the decoction, filter, and concentrate the filtrate to a clear paste with a relative density of 1.1 to 1.25 (80°C), put Cold, add ethanol to make the alcohol content reach more than 65%, stir well, let it stand for more than 24 hours, filter, recover ethanol from the filtrate and concentrate to a relative density of more than 1.0 (about 70°C), add 2 times the amount of dry paste The gelatinized starch is spray-dried to obtain powder, and then subjected to one-step granulation, granulation, tabletting and film coating to obtain 1600 tablet preparations IV-A of the present invention.

Example 8 Tablet 4-2

With reference to Example 7, the difference is: add water 8 times. That is the tablet preparation IV-B of the present invention.

The following examples will investigate the performance of the Chinese medicine composition of the present invention

Test purpose: To observe the antiviral, antibacterial, antipyretic, antitussive, expectorant, antiasthmatic and anti-inflammatory effects of the Chinese medicine composition of the present invention, with the granule I-A of Example 1 as the test sample.

experiment material

1. Drugs and reagents (* are supplementary test contents)

Preparation of the present invention: the granule I-A of the present invention of Example 1.

Content: equivalent to crude drug 2.45g/g granules.

Blank control (excipient): self-made by the inventor. (with reference to the method for preparing granules in Example 1, made from sucrose and citric acid fine powder, the ratio of the two is 2.99: 0.01)

Bacterial endotoxin: national standard product, batch number: 924, China Institute for the Control of Pharmaceutical and Biological Products.

Streptococcus pneumoniae: bacteria number: 31001, batch number: 20, as a standard strain, approved by the China Institute for the Control of Pharmaceutical and Biological Products.

Respiratory syncytial virus (RSV): standard strain Long strain, Vero cell monolayer culture medium. TCID50=10-6. Provided by Wuhan Institute of Virology, Chinese Academy of Sciences.

Analgin: batch number: 950810, Shenyang Fifth Pharmaceutical Factory.

Jizhi syrup: batch number: 950121, produced by Sichuan Fuling Pharmaceutical Factory

※Batch number: 980907104, produced by Fuling Pharmaceutical Factory of Taiji Group.

Aspirin: batch number: 950710, Jinyang Pharmaceutical Factory, Taiyuan, Shanxi, China.

Sodium phenobarbital: batch number: 951124, Shanghai Xinya Pharmaceutical Company.

※Hydrocortisone: produced by Shenyang No. 1 Pharmaceutical Factory, batch number: 950605.

Ammonium chloride: batch number: 950608, Beijing Xiangyang Pharmaceutical Factory.

Shuanghuanglian granule: batch number: 970101, Harbin Tiangong Pharmaceutical Co., Ltd.

Shuanghuanglian Oral Liquid: Batch No. 971103 41, Zhengzhou Zhongsheng Pharmaceutical Factory, China.

2. Drug preparation

Before use, prepare different concentrations with distilled water, and administer in equal volumes.

3. Animals

Kunming mice and SD rats were provided by the Experimental Animal Center of Dalian Medical University. Certificate number: Liaoshi Dongzi No. 522, ordinary first-class experimental animals.

Balb/c mice were provided by the Hubei Medical Science Animal Experiment Center. Certificate No. 042.

※Kunming white mice, half male and half male, weighing 18-22g.

Wistar rats, half male and half male, weighing 200-250g.

Guinea pigs, half male and half male, body weight 252.1±46.6g.

The above animals were purchased from the Animal Breeding Room of Shenyang Pharmaceutical University, the animal certificate number: Liaoshidongzi No. 033, and the experimental animal environmental facility qualification certificate number: Liaoshidongzi No. 036.

4. Instrument

Model 751 UV spectrophotometer.

Laboratory temperature during the test: 18-22°C.

Embodiment 9 In vivo test of Chinese medicine composition of the present invention against respiratory syncytial virus

(1) Determination of virus virulence

①Infection with RSV Clinical: 5 Balb/c mice were infected with cell-cultured virus by intranasal instillation, and 50-60 μl of the original solution was used for intranasal instillation. 24h after infection, the mice appeared hairy, less active, less food and other symptoms. After the first 3-4 days, the symptoms improved, and the appetite and spirit recovered. On the 8th day, the animals were dissected, the blood was collected, the blood was separated, and the lungs were obtained.

② Detection of serum RSV antibody by agar diffusion method: using RSV-McAb antibody as a control, sample serum was diluted 1:50, 1:100. After adding the sample overnight at 37°C, precipitation lines appeared, especially in the 1:50 sample.

③ Mouse lung homogenate, use 10% mouse lung suspension supernatant (filtered and cleaned), and culture in Vero to determine RSV50=10 ^-1--3

Table 1 Virus virulence assay results

(2) drug antiviral test

Balb/c mice were given nasal drops of 50 μl of RSV virus stock solution per nostril, and the administration was started after 4 hours, and the dosage shown in Table 2 was continuously administered for 8 days, once a day. On the 8th day after the administration, the mice were dissected, the blood was collected to separate the serum, and the RSV antibody was detected by indirect immunofluorescence staining; the pathological changes of the lungs were observed; the virus titer (TCID50) of the lung suspension in Vero cells was measured.

① Grouping and administration

Get 110 female 6-week-old Balb/c mice, with a body weight of 18-22 grams, and randomly divide them into eight groups (see Table 2): the first group is a normal control group (mice are not infected with RSV), equal volume of distilled water; The second group is infected with RSV to the eighth grade; the second group is the distilled water group; the third group is the blank control group; the fourth group is the morpholine group, the dose is 0.01g/kg/d; the fifth group is the Shuanghuanglian oral liquid Group, dosage is 11.0ml/kg/d; The 6th group is the small dose group (6g/kg/d) of granule I-A of the present invention; The 7th group is the middle dose group (9g/kg/d) of granule I-A of the present invention The eighth group is the large dose group (12.5g/kg/d) of granule I-A of the present invention. ig administration for eight days, once a day.

Table 2 Anti-RSV-Balb/c mouse in vivo test grouping of preparation of the present invention

Note: The mice in the normal control group were not infected with RSV.

② Determination of serum RSV antibody

Serum was diluted 1:50 and 1:100, and serum RSV antibody was detected by indirect immunofluorescence using RSV-McAb and Vero cells. The results are shown in Table 3.

Table 3Balb/c mouse serum RSV antibody assay results

n: number of animals

③Determination of virus titer

On the eighth day after the administration of Balb/c mice, a mouse lung suspension was prepared, and the virus titer was measured in Vero cells. The results are shown in Table 4.

The measurement result of table 4 lung suspension virus titer

④ On the eighth day after the administration of Balb/c mice, the lung tissues of the mice were taken for embedding in paraffin, sectioned, stained with HE, and the lung lesions were observed under a light microscope (×100,×200):

The small blood vessels in the alveoli of individual mice in C1 and C2 groups were slightly dilated;

The lung tissues of mice in groups C3, B1, B2, and A1 were normal;

The small blood vessels in the alveolar walls of mice in groups A2 and A3 were significantly dilated and congested, accompanied by focal hemorrhage in the alveoli.

See Figures 1, 2, 3, 4.

In summary, the preparation of the present invention shows in the anti-RSV mouse in vivo test that the oral granule I-A9g-12.5g/kg/d of the present invention has obvious anti-RSV effect, and compared with the matched group, there is a significant difference. The negative rate of immunofluorescence detection antibody was 94.4%, which was close to the anti-RSV effect of the positive control drug morpholine; rat lung tissue sections showed that after 8 days of treatment with granule I-A of the present invention, the lung tissue returned to normal, while the negative control group showed pneumonia performance ; After treatment with this sample, the mouse lung suspension has not detected the virus titer in Vero cell culture. The above test results show that the preparation of the present invention has obvious anti-respiratory syncytial virus (RSV) effect.

Embodiment 10 antibacterial test of Chinese medicine composition of the present invention

(1) In vivo protective effect on mice infected with Streptococcus pneumoniae

Take 90 Kunming mice and divide them into 6 groups at random. Positive control group is Shuanghuanglian granule group (ig80% Shuanghuanglian granule 25ml/kg, equivalent to Shuanghuanglian 20g/kg); 15 animals in each group, administered twice a day (once at 9:00 am and once at 3:00 pm) After 7 days of prophylactic administration, infect mice with the Streptococcus pneumoniae bacterium liquid (bacteria liquid concentration is 106/ml) cultivated in serum broth 18 hours, intraperitoneal injection, every mouse 0.5ml. After infection, each group continued ig administration according to the original dose for 7 days, observed the reaction of animals twice a day, and recorded the number of dead animals. The results are shown in Table 5.

Table 5 preparation of the present invention is to the in vivo protective effect of Streptococcus pneumoniae infection mice

As can be seen from Table 5, the granule I-A of the present invention can reduce the number of animal deaths when used in large and medium doses, and has a certain antibacterial effect.

(2) Antibacterial effect in vitro (test tube double dilution method)

Streptococcus pneumoniae strains were taken for enrichment culture (37°C, 6 hours), and diluted with broth to a 1:105 test bacterial solution. The sample was made into a 1 g/ml sample solution (PH=7.2) with broth, and three groups of sterilized test tubes were taken, 10 in each group. Add 0.5ml of sample solution to each test tube, then perform two-fold dilution for each group, and use the last tube as a negative control. Add 0.5ml of the test bacteria solution to each test tube, mix well, incubate the three groups of test tubes in a 37°C incubator for 18 hours and observe the results. The experiment was repeated three times, and the results are shown in Table 6.

Table 6 preparation of the present invention antibacterial test results in vitro

The MIC of Shuanghuanglian is 0.125g/ml, the MIC of the granule I-A of the present invention is 0.25g/ml, and the auxiliary materials are not antibacterial.

As can be seen from Table 6, the granule I-A of the present invention has a certain antibacterial effect in the in vitro antibacterial test.

The antipyretic test of embodiment 11 Chinese medicine composition of the present invention

Get SD rats, male and female half and half, body weight 160-180 grams, measure the anus temperature with an anal thermometer, measure once every half an hour, measure twice altogether, take the average temperature of two times as the normal body temperature of this rat. Select rats with a temperature difference of less than 0.5°C twice and a normal body temperature of 37.0-38.0°C, intraperitoneally inject bacterial endotoxin (600Eu/Kg), measure body temperature once an hour later, and select rats whose body temperature rises by 1-2°C 60 Only, be divided into 6 groups at random: distilled water control group (the distilled water of ig equal volume); Blank control group (the excipient of ig equal volume); , equivalent to granule 25g/kg, equivalent to crude drug 61.3g/kg, about 4.92 times of clinical dose); test substance middle dose group (ig50% granule I-A solution 25ml/kg of the present invention, equivalent to granule 12.5g/kg, equivalent to crude drug 30.7g/kg, about 2.46 times of clinical dose); Test substance low dose group (ig 25% granule I-A solution 25ml/kg of the present invention, equivalent to granule 6.25g/kg, equivalent to crude drug 15.3g/kg, about clinical Dosage 1.23 times); Sulpyrine control group (ig8% Sulpyrine solution 25ml/kg); Every group of 10, ig administration once, body temperature was measured once every half hour after administration, surveyed 6 times altogether. Record the body temperature, calculate the rise (fall) value of body temperature and pyrogenic temperature after administration, carry out t test, the results are shown in Table 7, Figure 5.

As can be seen from Table 7, the granule I-A of the present invention has obvious heat-clearing effect when the two doses are large and medium. The heat-clearing effect of Analgin is also very significant, which is equivalent to that of the high-dose group.

The antitussive test of embodiment 12 Chinese medicine composition of the present invention

(1) Ammonia-induced coughing in mice

Get 60 Kunming mice, half male and half female, with a body weight of 18-22 grams, and are randomly divided into 6 groups: distilled water control group (distilled water with equal volume of ig); blank control group (vehicle with equal volume of ig); High dose group (ig200% granule I-A solution 25ml/kg of the present invention, equivalent to granule 50g/kg, equivalent to crude drug 122.5g/kg, approximately 4.84 times the clinical dose); middle dose group (ig100% granule of the present invention) Agent I-A solution 25ml/kg, equivalent granule 25g/kg, equivalent crude drug 61.3g/kg, about 2.42 times of clinical dose); Test substance low dose group (ig granule I-A solution 25ml/kg of the present invention, equivalent granule 12.5g /kg, equivalent to crude drug 30.6g/kg, approximately 1.21 times the clinical dose); Jizhi syrup control group (ig former drug solution 50ml/kg, approximately equivalent to the dose in the test substance). There were 10 animals in each group. Dosing for seven days, once a day, 1 hour after the last administration, put the mice in a 500ml beaker, cover the beaker with a plate, spray ammonia water into the beaker quantitatively with a spray device, and then observe and record the cough latency of the mice and the number of times of coughing within 2 minutes, the results are shown in Table 8, as can be seen, compared with the blank control group, the test substance group can obviously prolong the cough latency and reduce the number of coughs, which is statistically very significant through the t test (p＜0.01 , p<0.05), and showed a good dose-effect relationship. The antitussive effect of Jizhi syrup is also very significant, which is equivalent to that of the middle dose group.

The antitussive action of table 8 preparation of the present invention (the mouse ammonia water induces asthma method)

^* P＜0.05 ^** P＜0.01 (compared with blank control group)

※(2) guinea pig citrate cough method

47 guinea pigs, weighing 132.9±20.2g, were randomly divided into five groups. The first group of guinea pigs is given intragastric equal volume normal saline; The second group of guinea pigs is given gastric juice 30ml/kg; 40 minutes after the last administration, put the guinea pig in a 700ml glass bell jar, spray 17.5% citric acid solution into the bell jar for 10 seconds, observe the cough latency of the guinea pig and cough within 5 minutes Times, the data were subjected to t-test, and the results are shown in Table 9.

Table 9 The preparation of the present invention causes guinea pigs to cough to the influence of oxalic acid

Note: *P<0.05 compared with normal saline group

**P<0.01 compared with normal saline group

***P<0.001 compared with normal saline group

As can be seen from the data in Table 9, the granule I-A of the present invention has a more obvious effect of inhibiting guinea pig cough caused by citric acid, can significantly prolong the cough latency of guinea pigs, and significantly reduce the number of coughs in 5 minutes.

The expectorant test of embodiment 13 Chinese medicine composition of the present invention

(1) Rat capillary glass tube sputum volume method

Take 60 SD rats, half male and half male, weighing 180-220 grams, and randomly divide them into 6 groups. The positive control group is the ammonium chloride group (25ml/kg of ammonium chloride solution prepared by ig, equivalent to 1g/kg of ammonium chloride). Fasting for 12 hours, anesthetized by intraperitoneal injection of sodium phenobarbital (100mg/kg), fixed in supine position. Cut the skin in the middle of the neck and separate the trachea. Use a sharp syringe needle to pierce a small hole between the two cartilage rings in the middle of the lower border of the thyroid cartilage, and then insert a glass capillary so that the capillary just touches the bottom surface of the trachea to suck the sputum from the rear of the trachea. When the capillary is filled with sputum, replace it with another one immediately. The phlegm-reducing effect of the drug was evaluated by the length of the sputum sucked by the capillary. Record the normal secretion 2 hours before the administration, administer once according to the dose indicated above, continue to observe for 4 hours, and record the secretion. The average hourly secretion was compared before and after administration. The results are listed in Table 10. It can be seen that compared with the blank control group, the test substance group can significantly increase the amount of sputum discharge, which is very statistically significant (P<0.01) through the t test, and there is a dose-effect relationship. The phlegm-reducing effect of ammonium chloride is also very significant, which is equivalent to that of the high-dose group.

The phlegm-reducing effect of table 10 preparation of the present invention (capillary glass tube expectorant volume method)

**P＜0.01 (compared with blank control group)

※(2) Phenol red method for mouse trachea

Fifty Kunming mice, half male and half female, weighing 20.3±1.1 g, were randomly divided into five groups, 10 mice in each group. The first group of mice is orally administrated with equal volume normal saline; the second group of mice is orally administrated with acute branch syrup 30ml/kg; , 7.5g/kg, 30 minutes after the administration, intraperitoneally inject 0.1ml/10g body weight of 5% phenol red, 30 minutes after the injection of phenol red, kill the mice, and peel off the tissues around the trachea. Cut off a section of trachea from under the thyroid cartilage to the branch of the trachea, put it into a test tube filled with 2.0ml of normal saline, add 2 drops of 5% NaOH after 10 minutes, measure the optical density at a wavelength of 546nm, and use the phenol red standard The excretion of phenol red was calculated from the curve, and the significance of the difference compared with the control group was shown in Table 11 for the results.

Table 11 The impact of the preparation of the present invention on the secretion of phenol red in the mouse trachea

Note: *P<0.05 compared with normal saline group

**P<0.01 compared with normal saline group

***P<0.001 compared with normal saline group

Shown by the data of table 11, granule I-A of the present invention has obvious expectorant effect, and large and medium doses have obvious promoting effect to phenol red excretion, and excretion increases, and acute branch syrup group effect is the most obvious, and normal saline Compared with the control group, P<0.001.

The antiasthmatic effect of embodiment 14 Chinese medicine composition of the present invention

50 guinea pigs, half male and half male, weighing 120±17 g, were randomly divided into five groups, 10 guinea pigs in each group. The first group of animals gavages equal volume normal saline; The second group of animals gavages acute branch syrup 3ml/100g body weight; The third-five groups gavage granule I-A30g/kg of the present invention, 15g/kg and 7.5g/kg , continuous administration for 7 days, in the last 40 minutes of administration, put the guinea pigs in a 700ml glass bell jar, spray them with 2% acetylcholine and 0.1% histamine mixture for 10 seconds at regular intervals, and observe the guinea pigs for wheezing The incubation period (that is, the time from the beginning of spraying to the onset of asthma, extreme difficulty in breathing, until convulsions and falls), the results are shown in Table 12.

Table 12 The antiasthmatic effect of the preparation of the present invention on guinea pigs

Note: *P<0.05 compared with normal saline group

**P<0.01 compared with normal saline group

***P<0.001 compared with normal saline group

As can be seen from the data in Table 12, the granule I-A of the present invention has a more obvious effect of inhibiting dyspnea and wheezing caused by guinea pig bronchospasm induced by the Ach-His mixed solution, and can significantly prolong the incubation period of wheezing. Invention granule I-A has obvious antiasthmatic effect.

Anti-inflammatory effect of embodiment 15 Chinese medicine composition of the present invention

(1) Mouse ear xylene-induced inflammation method

Get 60 Kunming male mice, body weight 26-30 grams, be divided into 6 groups at random: distilled water control group (distilled water of equal volume of ig); Blank control group (excipient of equal volume of ig); Group (ig 200% granule I-A solution 30ml/kg of the present invention, equivalent granule 60g/kg, equivalent crude drug 147.0g/kg, about 5.80 times of clinical dose); dosage group (ig 100% granule I-A of the present invention Solution 30ml/kg, corresponding granule 30g/kg, corresponding crude drug 73.5g/kg, about 2.90 times of clinical dose); Test substance low dose group (ig 50% granule I-A solution 30ml/kg of the present invention, corresponding granule 15.0g /kg, equivalent to crude drug 36.8g/kg, approximately 1.45 times the clinical dose); aspirin group (aspirin solution 25ml/kg for ig, equivalent to aspirin 0.2g/kg). Ig was administered for ten days, once a day, and 0.05 ml of xylene was applied to the right ear of the mouse 1 hour after the last administration to cause inflammation. After 2 hours, the mice were sacrificed by cervical dislocation, and the two ears were cut off along the base line of the auricles, and round ear pieces were punched in the same part of the left and right ear pieces of the mouse with a hole punch with a diameter of 9 mm, and weighed. The weight difference between the two ear pieces As the degree of swelling, carry out t test, and calculate the swelling inhibition rate of each group according to the following formula, the results are shown in Table 13, it can be seen that compared with the blank control group, the test substance can significantly inhibit the swelling of small ear caused by xylene, after t test, Statistically very significant (P<0.01), and there is a dose-effect relationship. The anti-inflammatory effect of aspirin was also very significant, which was comparable to that of the high-dose group.

The impact of table 13 preparation of the present invention on mouse ear swelling caused by xylene

**P＜0.01 (compared with blank control group)

※(2) Rat toe egg white inflammation method

Take 50 rats, weighing 252.1±46.6g, half male and half male, and randomly divided into five groups, 10 rats in each group. The first group gavages equal volume distilled water; Second group-the fourth group gavages granule I-A30g/kg of the present invention, 15g/kg and 7.5g/kg, continuous gavage administration 7 days; The fifth group rat On the seventh day, hydrocortisone 30 mg/kg was subcutaneously injected, and all animals were subcutaneously injected with 0.1 ml of fresh egg white in the direction of the joint in the right hind foot of all animals 20 minutes after the last administration, respectively at 30, 45, At 60 minutes and 90 minutes, respectively, the degree of swelling of the foot was measured with a rat foot swelling instrument, and the results are shown in Table 14.

Paw swelling = volume of the foot after egg white injection - volume of the fore foot after egg white injection

The impact of table 14 preparation of the present invention on rat paw swelling

Note: *P<0.05 compared with normal saline group

***P<0.001 compared with normal saline group

The data in Table 14 shows that the preparation of the present invention has an obvious effect of inhibiting rat paw swelling.

Conclusion: The preparation of the present invention has significant antiviral, antipyretic, antitussive, expectorant, antiasthmatic, anti-inflammatory and certain antibacterial effects.

In summary, through the research on the main pharmacodynamics test, the effectiveness and safety of the preparation of the present invention have been fully proved, which not only provides a basis for clinical trials of the preparation of the present invention, but also provides a basis for safe drug use in clinical trials. Reference dose.

Embodiment 16 clinical experiment

Granules of the present invention I-A Control group: Jizhi Granules

According to the Phase II clinical trial plan, a multi-center randomized double-blind double-dummy controlled method was used for clinical observation research. All 213 subjects were from the pediatric clinics, wards or emergency observation rooms of three national clinical pharmacology research bases (the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, and the First Affiliated Hospital of Henan University of Traditional Chinese Medicine). . Among the 213 cases, 208 cases were included in the statistics, including 102 cases in the test group, except for 5 cases that did not meet the requirements of the test plan, including 73 outpatient cases, accounting for 71.57%, 21 inpatient cases, accounting for 20.59%, and observation room cases. 8 cases, accounting for 7.84%; 106 cases in the control group, including 73 outpatient cases, accounting for 68.87%, 24 inpatient cases, accounting for 22.64%, 9 cases of observation room, accounting for 8.49%. Comparing the sources of cases between the two groups, X ² =0.1820, P>0.05, the difference has no significant significance.

Table 15 Comparison of total curative effect of acute bronchitis in two groups of patients

Note: The total effective rate refers to the recovery rate + marked rate (that is, the marked rate of cure), the same below.

Ridit analysis: U=2.4404, P<0.05. The difference between the two groups was significant.

Typical cases

Case 1:

GY, female, 5 years old. Trials began on March 5, 2001. Random number: A10.

Chief Complaint: Cough for 2 days.

History of present illness: Cough started 2 days ago and became significantly worse 1 day ago. Now the cough is frequent, the amount of sputum is not much, the sputum is yellow and white, thirsty, the urine is not yellow, and the stool is dry.

Physical examination: body temperature 36.3 ℃, clear mind, spirit is still good, breathing flat. Pharyngeal congestion, rough breath sounds in both lungs, occasionally dry sounds, strong heart sounds, heart rate 85 beats/min, no murmurs, and soft abdomen. Red tongue, yellow coating, slippery pulse.

Laboratory tests:

Blood routine: WBC8.4×109/L, N30.8%, HB112g/L, RBC4.69×1012/L.

Chest X-ray: slightly more lung markings.

Diagnosis and syndrome differentiation: Acute bronchitis in children (phlegm-heat cough syndrome)

Diagnosis and treatment process: After the diagnosis, the test drug No. A10 was administered. Give each 15ml of medicine of the present invention and Jizhi granule simulated medicine, 3 times every day, orally. After 3 days of treatment, the cough was alleviated, the sputum was as usual, the dry sound of both lungs disappeared, and the breath sound was still rough. After 5 days of treatment, the symptoms of cough and phlegm disappeared, the body temperature was 36.5°C, the throat was not red, the breathing sounds of both lungs were clear, the heart sounds were strong, and the heart rate was 86 beats/min. Body of the tongue is light red, fur is thin, and pulse is flat. Recheck blood routine: WBC8.7×109/L, N44.9%, HB126g/L, RBC4.83×1012/L. X-ray chest X-ray still showed no changes in the heart and lungs. According to the curative effect evaluation standard, the total curative effect is cured (0/15=0), and the syndrome curative effect is markedly effective (0/11=0). In test. No adverse reactions were found, and the safety evaluation was grade one.

Case 2:

ZMY, female, 4 years old. On April 4, 2001, he was hospitalized for treatment. Random number: B D10.

Chief Complaint: Cough for 2 days.

History of present illness: The child started to cough 2 days ago. , Cough bursts, there is not much sputum, the sputum is yellow and white, the urine is not yellow, and the stool is not dry.

Physical examination: body temperature 37.2 ℃, clear mind, spirit is still good, breathing flat. Pharyngeal congestion, rough breath sounds in both lungs, strong heart sounds, heart rate 120 beats/min, no murmur heard, and soft abdomen. Red tongue, yellow fur, rapid pulse.

Laboratory tests:

Blood routine: WBC5.0×109/L, L32.9%, N59.0%, HB119g/L, PLT222×109/L.

Urine routine, stool routine (-).

Chest X-ray: Increased and disordered lung markings.

Diagnosis and syndrome differentiation: Acute bronchitis in children (Children cough with phlegm-heat syndrome)

Diagnosis and treatment process: After the diagnosis, the test drug BD10 was administered. Give each 15ml of medicine of the present invention and Jizhi granule simulated medicine, 3 times every day, orally. After 1 day of treatment, the cough was alleviated. After 4 days of treatment, the symptoms of cough, phlegm, and dry stool disappeared, the body temperature was 36.2°C, the breath sounds in both lungs were clear, the heart sounds were strong, and the heart rate was 110 beats/min. Body of the tongue is light red, fur is thin, and pulse is flat. Check blood routine: WBC10.0×109/L, L19%, N77.0%, HB143g/L, PLT179×109/L. X-ray chest X-ray: (-). According to the curative effect evaluation standard, the total curative effect and syndrome curative effect were all rated as recovery. In the test, no adverse reactions were found, and the safety evaluation was grade one.

Case 3:

YC, male, 2 years old. Trials began on July 3, 2001. Random number: C D06.

Chief complaint: cough, low fever for 1 day.

History of present illness: Cough and fever started 1 day ago. Now cough frequently, there is phlegm sound in the throat, low-grade fever, no thirst, no yellow urine, and normal stool.

Physical examination: body temperature 37.9 ℃, clear mind, spirit is still good, shortness of breath, 31 times/min. Pharyngeal congestion, rough breath sounds in both lungs, occasional sputum sounds, strong heart sounds, heart rate 120 beats/min, no murmurs, and soft abdomen. Red tongue, yellow fur, purple fingerprints.

Laboratory tests:

Blood routine: WBC3.7×109/L, N75.8%, HB125g/L, RBC4.25×1012/L, PLT129×109/L. Urine routine, stool routine: (-).

Chest X-ray: thick and heavy lung texture.

Diagnosis and syndrome differentiation: Acute bronchitis in children (phlegm-heat cough syndrome)

Diagnosis and treatment process: After the diagnosis, the test drug No. C D06 was given. Give each 15ml of medicine of the present invention and Jizhi granule simulated medicine, 3 times every day, orally. After 3 days of treatment, the low-grade fever disappeared, the number of coughs decreased, and there was still phlegm in the throat. The body temperature was normal, the breathing was stable, and the breath sounds in both lungs were rough. After 5 days of treatment, the symptoms of cough and phlegm disappeared, the body temperature was 36.4°C, the throat was slightly red, the breathing sounds of both lungs were clear, the heart sounds were strong, and the heart rate was 86 beats/min. Body of the tongue is light red, fur is thin, fingerprint is lavender. Recheck blood routine: WBC5.2×109/L, N77.9%, HB137g/L, RBC4.18×1012/L, PLT117×109/L. Urine routine, stool routine: (-). X-ray chest X-ray still showed no changes in the heart and lungs. According to the curative effect evaluation standard, the total curative effect is cured (0/15=0), and the syndrome curative effect is markedly effective (0/11=0). The safety evaluation is level one.

The above results show that the granule I-A of the present invention is a new traditional Chinese medicine with clearing lung and resolving phlegm, relieving cough and relieving asthma, and promoting blood circulation and removing blood stasis as main effects, and is mainly used for treating children with acute bronchitis with phlegm-heat cough syndrome. The test results show that the total curative effect of the test group, the recovery rate is 34.31%, and the total effective rate (cure + marked rate) is 86.27%; while the recovery rate of the control group is 21.70%, and the total effective rate is 74.53%. Comparing the two groups, the curative effect of the experimental group was higher than that of the control group, and the difference was significant. The cure rate of the test group for phlegm-heat cough syndrome was 27.45%, and the total effective rate was 90.20%; while the cure rate of the control group was 19.81%, and the total effective rate was 75.47%. There was no significant difference between the two groups. The mean values of the total integral value and syndrome integral value difference of the test group were also higher than those of the control group, and the difference was significant.

According to the statistical analysis results of the improvement of various indicators, after treatment, symptoms such as cough and expectoration, abnormal tongue pulse and lung signs were significantly improved compared with those before treatment, and the improvement effect of cough and abnormal tongue coating in the experimental group was better than that in the control group. , the difference is significant. Before treatment, there was no significant difference in white blood cell count and abnormalities of chest X-ray between the two groups, which were comparable. After treatment, the white blood cell counts in the two groups were significantly improved, and the abnormalities of the chest X-ray were also improved to a certain extent, but there was no significant difference between the two groups. It shows that the two drugs have similar improvement effects on the increase of white blood cell count and the thickening of lung markings on X-ray chest film. There was no significant difference in the positive rate of nasopharyngeal virus detection and bacterial culture of throat swab between the two groups before treatment; there was no significant difference in the negative conversion rate after treatment between the two groups, but the negative conversion rate of the two groups Both are above 80%, indicating that the two medicines have good antiviral and antibacterial effects.

Of the 213 children in this group, except for one case (case in the test group) who experienced dry lips during treatment (the safety evaluation was "Level 2"), no adverse reactions were found, and the safety evaluation was "Level 1". ". Laboratory indicators included hematuria and stool routine, liver and kidney function, and electrocardiogram changes before and after treatment, and no abnormal changes related to the test drug were found. Illustrate that granule I-A of the present invention is clinically applied by test dose, and is safer.

in conclusion

The granule I-A of the present invention is applied by test dose and 5-day course of treatment, and has good curative effect to infantile bronchitis phlegm-heat cough syndrome, and it is all obviously higher than in aspects such as overall curative effect, improvement of main cough symptoms and reduction of total scores of TCM syndromes. The control drug (Jizhi Granules) has fully confirmed its efficacy in clearing the lungs and resolving phlegm, relieving cough and relieving asthma. In addition, the results of nasopharyngeal virus detection and throat swab bacterial culture in children before and after taking the medicine have also clinically confirmed the efficacy of this product. It has antiviral and antibacterial effects (the negative conversion rate of positive phase III is 100%), and no obvious toxic and side effects are seen.

Claims (10)

1. Chinese medicine composition for the treatment of diseases in respiratory system, its crude drug consists of, to make the 1000g finished product:

Processed with honey Herba Ephedrae 75-175g Gypsum Fibrosum 750-1750g

Semen Armeniacae Amarum (parched) 75-175g processed with honey Cortex Mori 75-175g

Semen Descurainiae (parched) 30-120g Radix Angelicae Sinensis 125-250g

Radix Salviae Miltiorrhizae 125-250g Pheretima 75-175g

Bombyx Batryticatus (parched) 75-175g Radix Glycyrrhizae 75-175g.

2. compositions according to claim 1, wherein crude drug consists of, to make the 1000g finished product:

Processed with honey Herba Ephedrae honey 100-150g Gypsum Fibrosum 1000-1500g

Semen Armeniacae Amarum (parched) 100-150g processed with honey Cortex Mori 100-150g

Semen Descurainiae (parched) 50-100g Radix Angelicae Sinensis 150-226g

Radix Salviae Miltiorrhizae 150-226g Pheretima 100-150g

Bombyx Batryticatus (parched) 100-150g Radix Glycyrrhizae 100-150g.

3. compositions according to claim 2, wherein crude drug consists of, to make the 1000g finished product:

Processed with honey Herba Ephedrae 112-137g Gypsum Fibrosum 112-1370g

Semen Armeniacae Amarum (parched) 112-137g processed with honey Cortex Mori 112-137g

Semen Descurainiae (parched) 68-82g Radix Angelicae Sinensis 170-206g

Radix Salviae Miltiorrhizae 170-26g Pheretima 112-137g

Bombyx Batryticatus (parched) 112-137g Radix Glycyrrhizae 112-137g.

4. compositions according to claim 3, wherein crude drug consists of, to make the 1000g finished product:

Processed with honey Herba Ephedrae 125g Gypsum Fibrosum 1250g

Semen Armeniacae Amarum (parched) 125g processed with honey Cortex Mori 125g

Semen Descurainiae (parched) 75g Radix Angelicae Sinensis 188g

Radix Salviae Miltiorrhizae 188g Pheretima 125g

Bombyx Batryticatus (parched) 125g Radix Glycyrrhizae 125g.

5. according to the described compositions of the arbitrary claim of claim 1 to 4, the dosage form that can prepare is selected from granule, capsule, oral liquid, unguentum or tablet.

6. the described preparation of compositions method of the arbitrary claim of claim 1 to 4, it comprises the steps:

(1) takes by weighing the flavor of ten described in the described compositions of the arbitrary claim of claim 1 to 4 crude drug, add 20～3 times in water, decoct each 0.5～4 hour 1～4 time;

(2) collecting decoction filters, and filtrate is left standstill;

(3) getting supernatant, to be evaporated to relative density be the clear paste of 1.0-1.3 in the time of 50～80 ℃.

7. preparation method according to claim 6, it comprises the steps:

(1) takes by weighing described ten flavor crude drug, add 20～4 times in water, decoct each 0.5～4 hour 2～4 times;

(2) collecting decoction filters, and filtrate is left standstill;

(3) getting supernatant, to be evaporated to relative density be the clear paste of 1.0-1.3 in the time of 50～80 ℃.

The described compositions of the arbitrary claim of claim 1 to 4 preparation antiviral, antibiotic, analgesic, antitussive, eliminate the phlegm, relieving asthma or anti-inflammatory drug in application.

9. application according to claim 8, it is the application in preparation treatment acute bronchitis or the convalescent phlegm-heat cough card of pneumonia medicine.

10. test right requires the method for the active matter content of the described compositions of 1 to 4 arbitrary claim, and it comprises:

It is an amount of that the preparation precision of reference substance solution takes by weighing the ephedrine hydrochloride reference substance, adds water and make every 1ml and contain the 0.02mg reference substance solution;

The preparation weighting profit of need testing solution requires the described compositions of 1 to 4 arbitrary claim, carry out vapor distillation after adding sodium chloride and 40% sodium hydroxide solution, distillate is put in the measuring bottle that contains dilute hydrochloric acid, makes need testing solution with 40% sodium hydroxide solution adjust pH to 6.0-7.0;

Algoscopy is got above-mentioned two kinds of solution and is added the citric acid-sodium hydrogen phosphate buffer that contains bromothymol blue respectively, respectively adds chloroform again and extracts, and divides and gets chloroform layer, measures trap at 414nm wavelength place with spectrophotography, calculates promptly;

With the ephedrine hydrochloride is reference substance, contains Herba Ephedrae with ephedrine hydrochloride (C with the described compositions of the every 1g of Herba Ephedrae content in the spectrophotometry test sample ₁₀H ₁₅NOHCL) meter must not be less than 0.30mg.

Images