CN111097002A - Traditional Chinese medicine composition for clearing and nourishing throat and preparation method thereof - Google Patents

Abstract

The invention provides a medicinal and edible traditional Chinese medicine composition with the health-care functions of clearing and nourishing throat. The composition is prepared from a plurality of medicines such as honeysuckle, figwort root and the like, animal tests prove that the composition is safe and non-toxic, crowd tests prove that the composition has good effects on clearing and nourishing throat, and is suitable for popularization and application.

Description

Traditional Chinese medicine composition for clearing and nourishing throat and preparation method thereof

Technical Field

The invention relates to a traditional Chinese medicine composition for clearing and nourishing throat and a preparation method thereof, wherein the components contained in the composition are all listed in a Chinese medicinal material catalogue with homology of medicine and food, and the composition belongs to the related field of food and health care products.

Background

Chronic pharyngitis is one of the most common diseases of otolaryngology, is diffuse pharyngeal lesion caused by chronic infection, is mostly generated in adults, is often accompanied by other upper respiratory diseases, and is caused by repeated attack of acute pharyngitis, rhinitis and nasal sinusitis due to pus stimulation of pharyngeal portion or nasal obstruction to open mouth and breathe.

Generally without obvious systemic symptoms. The main clinical manifestations are pharyngeal discomfort, dryness, foreign body sensation or mild pain, dry cough, nausea, pharyngeal congestion with dark red color, and lymphatic bleb in the posterior pharyngeal wall. Chronic pharyngitis patient often clears throat and spits white sputum because of the increase of throat secretion.

Chronic pharyngitis often has a history of repeated attack of acute pharyngitis, or chronic mouth opening and breathing due to rhinopathy, excessive smoking and drinking, dry ambient air, dust, irritant gas pollution and the like. The expression is as follows: pharyngeal discomfort, pain, itching, dryness, burning sensation, smoking sensation, foreign body sensation, etc.; irritable cough, cough up in the morning and cough up secretions or even retching. The course of disease is more than 2 months, and symptoms are usually caused by catching cold, fatigue, lingering speech and the like. Chronic congestion and aggravation of pharyngeal region can be observed. Dark red, or dendritic congestion; proliferation of lymphatic follicles in the posterior pharyngeal wall, or enlargement of the lateral pharyngeal cord; the pharyngeal mucosa is hypertrophic or dry, atrophic, thinned, and attached with secretion.

Western medicine generally focuses on the treatment of pathogenic factors and local application, such as: mouthwash, with 2% perk acid solution, 3% saline and 1: 5000 furacilin solution can be used for repeated mouth rinsing, or 2% iodine glycerol and 5% strong protein silver solution can be used for pharyngeal wall, or iodine buccal tablet, domiphen, herba Menthae, etc. can be used for oral cavity, etc., and has certain function of relieving symptoms. Chinese patent medicines such as sarcandra glabra buccal tablets, watermelon frost and the like can also be selected for local symptomatic treatment. Smoking cessation and alcohol withdrawal are very important.

The traditional Chinese medicine treatment emphasizes treating the root cause of diseases, and the medicine is taken according to a dialectical typing method, so that the curative effect is better. The general administration is as follows: for yin deficiency fire type, decoction for nourishing yin and clearing lung-heat (radix Ophiopogonis, radix rehmanniae, radix scrophulariae, radix Paeoniae alba, Glycyrrhrizae radix, Gypsum Fibrosum, herba Menthae, Bulbus Fritillariae Cirrhosae powder, cortex moutan, folium Mori, etc.); for phlegm stagnation and blood stasis, add Xiaoluo Wan (radix scrophulariae, Concha Ostreae, Bulbus Fritillariae Cirrhosae, radix rehmanniae, radix Ophiopogonis, rhizoma Sparganii, thallus laminariae, Sargassum, etc.); for yin deficiency and fluid depletion type, it is often taken with pulse-activating decoction (white sun-dried ginseng, ophiopogon root, schisandra fruit, dendrobium stem, fragrant solomonseal rhizome, cogongrass rhizome, bamboo shavings, etc.) for each day.

Chronic pharyngitis is an intractable disease, the disease course is long, and no matter the medicine is western medicine or traditional Chinese medicine, the medicine has toxic and side effects after long-term administration. Therefore, the market urgently needs to present a health-care food which can be taken for a long time and has the effects of clearing and moistening the throat and is suitable for chronic pharyngitis patients to take for a long time.

The invention provides a medicinal and edible traditional Chinese medicine composition with the health-care functions of clearing and nourishing throat and a preparation thereof, in particular to an application of the composition in preparing medicines for treating chronic pharyngitis.

Disclosure of Invention

The invention aims to provide a medicinal and edible traditional Chinese medicine composition with the health-care functions of clearing and nourishing throat.

The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

30-42 parts of honeysuckle; 30-42 parts of radix scrophulariae; 25-35 parts of Chinese olive; 15-21 parts of platycodon grandiflorum; 15-21 parts of emblic leafflower fruit; 2.5-3.5 parts of momordica grosvenori; 0.1-0.14 part of menthol.

Preferably, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight:

30 parts of honeysuckle; 42 parts of radix scrophulariae; 25 parts of Chinese olive; 21 parts of platycodon grandiflorum; 15 parts of emblic leafflower fruit; 3.5 parts of momordica grosvenori; 0.1 part of menthol.

Or may preferably be:

42 parts of honeysuckle; 30 parts of radix scrophulariae; 35 parts of Chinese olive; 15 parts of platycodon grandiflorum; 21 parts of emblic leafflower fruit; 2.5 parts of momordica grosvenori; 0.14 part of menthol.

It is also preferable that:

36 parts of honeysuckle; 36 parts of radix scrophulariae; 30 parts of Chinese olive; 18 parts of platycodon grandiflorum; 18 parts of emblic leafflower fruit; 3 parts of momordica grosvenori; 0.12 part of menthol.

It is also preferable that:

35 parts of honeysuckle; 35 parts of radix scrophulariae; 28 parts of Chinese olive; 17.5 parts of platycodon grandiflorum; 17.5 parts of emblic leafflower fruit; 2.2 parts of momordica grosvenori; 0.11 part of menthol.

The active component of the medicinal and edible traditional Chinese medicine composition provided by the invention is prepared by the following steps:

(1) pulverizing Mentholum;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction, and filtering an extracting solution for later use:

(3) concentration: concentrating the extractive solution to obtain fluid extract; precipitating, filtering, collecting filtrate, recovering ethanol, and concentrating to obtain soft extract;

(4) and (3) drying: drying the thick paste obtained in the step (3) to obtain dry paste for later use;

(5) crushing: and (4) crushing the dry paste obtained in the step (4) to obtain the active component of the traditional Chinese medicine composition.

The preparation formulation of the medicinal and edible traditional Chinese medicine composition is selected from capsules, tablets, pills, powder, soft capsules or paste.

The preparation method of the medicinal and edible traditional Chinese medicine composition tablet comprises the following steps:

(1) pulverizing Mentholum;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction, and filtering an extracting solution for later use:

(3) concentration: concentrating the extractive solution to obtain fluid extract; precipitating, filtering, collecting filtrate, recovering ethanol, and concentrating to obtain soft extract;

(4) and (3) drying: drying the thick paste obtained in the step (3) to obtain dry paste for later use;

(5) crushing: crushing the dry paste obtained in the step (4) to obtain dry paste powder for later use;

(6) and (3) granulating: taking the dry paste powder, conventionally granulating, drying and finishing;

(7) total mixing: adding menthol powder into the granules after finishing the granules and mixing;

(8) tabletting: tabletting by conventional method.

The preparation method of the medicinal and edible traditional Chinese medicine composition tablet comprises the following steps:

(1) and (3) crushing menthol: weighing menthol, crushing, and sieving with a 100-mesh sieve for later use;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction twice, 1 hour each time, adding 12 times of water for the first time, adding 10 times of water for the second time, and filtering the extract for later use:

(3) concentration: concentrating the extracting solution under reduced pressure (the temperature is 60-80 ℃, the vacuum degree is 0.04-0.08 MPa) to obtain clear paste with the relative density of 1.08-1.12 (60 ℃); adding a proper amount of ethanol into the clear paste to ensure that the ethanol content is 70%, uniformly stirring, and standing for 48 hours at the temperature of 2-10 ℃; filtering, taking the filtrate, recovering ethanol under reduced pressure, and concentrating (at the temperature of 60-80 ℃ and the vacuum degree of 0.04-0.08 MPa) into thick paste with the relative density of 1.20-1.30 (at 60 ℃);

(4) and (3) drying: drying by adopting a vacuum belt type, wherein the temperature of a heating plate is 110-120 ℃, the vacuum degree is 0.08-0.10 MPa, and collecting dry paste for later use;

(5) crushing: pulverizing the dry extract obtained by vacuum belt drying, and sieving with 100 mesh sieve;

(6) and (3) granulating: putting the dry paste powder into a mixer, adding lactose, dextrin and erythritol, uniformly mixing, adding 80-90% ethanol to prepare a soft material, granulating by using a 16-mesh sieve, and drying at the temperature of below 60 ℃ to obtain the dry paste;

(7) straightening: putting the dried granules into a crushing and granulating machine, and granulating by using a conical sieve with the diameter of 1.5 mm;

(8) total mixing: adding the menthol powder, the magnesium stearate and the sucralose into the granules after finishing the granules, uniformly mixing in a mixer for 8 r/min, and mixing for 20 minutes;

(9) tabletting: tabletting, and controlling the weight of each tablet to be 0.8 g.

In the traditional Chinese medicine composition, the latin name of the raw material medicine as the active component and the processing method thereof come from traditional Chinese medicine dictionary (7 months in 1977, the first edition, Shanghai science and technology publishing Co., Ltd.) and Chinese pharmacopoeia (2005 edition, chemical industry publishing Co., Ltd.).

The traditional Chinese medicine composition can be prepared into any pharmaceutically acceptable conventional dosage forms, such as capsules, tablets, pills, powder, soft capsules or paste, according to the conventional preparation process, for example, the preparation process recorded in Vanbitsin traditional Chinese medicine pharmacy (Shanghai science Press 1997 12 months 1).

In the application of the invention, the traditional Chinese medicine composition is one of capsules, tablets, pills, powder, soft capsules or paste preparations, and in order to realize the dosage forms, pharmaceutically acceptable auxiliary materials are required to be added when the dosage forms are prepared, such as: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, and the like. The filler comprises: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; the disintegrating agent comprises: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crospolyvinylpyrrolidone, low-substituted hydroxypropylcellulose, croscarmellose sodium, etc.; the lubricant comprises: magnesium stearate, sodium lauryl sulfate, talc, silica, and the like; the suspending agent comprises: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, and the like; the adhesive comprises starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.; the sweetener comprises: saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, and the like; the flavoring agent comprises: sweeteners and various essences; the preservative comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate, eucalyptus oil, etc.; the matrix comprises: PEG6000, PEG4000, insect wax, etc. In order to realize the traditional Chinese medicine pharmacy, other pharmaceutically acceptable auxiliary materials (auxiliary materials recorded in each dosage form in the 12 th month and 1 st edition of Shanghai science Press 1997) are required to be added when preparing the dosage forms.

Chronic pharyngitis is a chronic disease with dry burning pain, foreign body sensation, discomfort, itching throat, little phlegm, dry cough and other symptoms as main symptoms, and is clinically divided into chronic simple pharyngitis, chronic hypertrophic pharyngitis, atrophic pharyngitis or dry pharyngitis. Patients often have pharyngeal discomfort, foreign body sensation, or irritable cough in the morning, especially in the morning with pronounced brushing, often accompanied by nausea. The chronic pharyngitis belongs to the field of the pharyngitis in the traditional Chinese medicine, and the first medical monograph in China is the first name of the pharyngitis in Huangdi's Canon. The literature also discloses a theory of yin and yang as well as questions: the combination of yin and yang is the obstruction of the throat. The pathogenesis of the throat disease is mainly yin deficiency of viscera, and the deficiency of lung yin causes the body fluid not to be infused upwards, so that deficient heat is internally flaming and scorching the throat; deficiency of kidney yin, insufficient body fluids, failing to nourish the throat, deficient fire goes up the throat along the channel. When yin deficiency and fluid deficiency occur, the throat fails to be nourished, and deficient fire may flow through the channel and end up in the throat, or may be attacked by wind-heat pathogen, causing lung-stomach stagnated heat, which may cause fire-heat steaming up and end up in the throat. In addition, liver failure in treating qi stagnation leading to depression of the throat; spleen failing to transport and transform, water-damp retention, dampness accumulation and phlegm generation, phlegm accumulation in throat. Fire, qi and phlegm obstructing each other, long-term depression and blood stasis in the throat. It is seen that the pathogenesis of the throat is mainly yin deficiency and fire hyperactivity, and the pathological products such as qi stagnation, phlegm coagulation and blood stasis are accumulated in local throats.

The medicine-food homologous traditional Chinese medicine composition provided by the invention is used for formulating the treatment principles of clearing heat and relieving sore throat, nourishing yin and cooling blood, and moistening lung and relieving cough according to the understanding of the etiology and pathogenesis of chronic pharyngitis by traditional Chinese medicine, and selects medicine-food homologous traditional Chinese medicines for clearing heat and detoxicating, nourishing yin and lowering fire, and ventilating lung and relieving sore throat and relieving cough, and aims to clear heat, promote fluid production, relieve sore throat and treat chronic pharyngitis in an auxiliary manner and relieve pharyngeal discomfort. The product is suitable for teachers, tour guides, specific personnel with much dust in working environment and other people susceptible to chronic pharyngitis, and can be taken for a long time. The good effect replaces the side effect possibly caused by taking the medicine, and the satisfactory effect is achieved.

In order to confirm the effects of the medicinal and edible composition of the invention on clearing and moistening throat, treating chronic pharyngitis and relieving pharyngeal discomfort, the following pharmacological and clinical tests were carried out on the active component (hereinafter referred to as the composition of the invention) prepared by the method of example 1.

Firstly, safety toxicology evaluation:

the composition of the invention is subjected to safety toxicology evaluation by the analysis and evaluation center of the national institutes of public health of western Sichuan university, and the test result shows that:

1. acute oral toxicity test that the acute oral MTD of SD rat is more than 15g/kg.bw and belongs to nontoxic class.

2. And (3) the genotoxicity tests, namely Ames test, mouse marrow pleochromatic erythrocyte micronucleus test and mouse teratospermia test, have negative results.

3. In a feeding test of a rat for 30 days, the highest dose is 100 times of the recommended human intake, the composition does not cause abnormal changes of important indexes such as the overall health condition, physiological and biochemical functions, organ tissue morphology and the like of the rat, and the initially estimated maximum non-effective dose is more than 8.0g/kg.bw (100 times of the recommended human intake).

The following is a safety toxicology evaluation test report

1 materials and methods

1.1 sample

The composition of the invention is sent to inspection by Shijiazhuang Ling pharmaceutical industry Co Ltd, recommended adult dose is 4.8 g/person/day, sealed, dried and stored. The samples were prepared and diluted with distilled water during the test.

1.2 Experimental animals and raising

The SPF-grade SD rats for acute toxicity test were provided by the institute for laboratory animals in human hospital of sichuan province of the medical academy of sichuan province (license number SCXK (chuan) 2013-15), and the other SPF-grade SD rats and kunming-breed mice were provided by the center for laboratory animals of the medical academy of traditional Chinese medicine of sichuan province (license number SCXK (chu) 2013-19). The animals are subjected to adaptive feeding and then are tested, in the whole test process, the animals are raised in a barrier-level animal room (license number: Sichuan experimental animal management Committee SYXK 2013-.

1.3 Main instruments and reagents

An ultraclean biological workbench, a constant-temperature incubator, an OLYMPUS microscope, an AU480 full-automatic biochemical analyzer (BeckmenCoulter), a Medonic M-series TD full-automatic blood cell analyzer (Boolean medical devices (Beijing) Co., Ltd., 2,4, 7-trinitro-9-fluorenone (TNF) is an AccuStandard product, coenzyme II is a Roche product, and sodium azide (NaN)₃) 1, 8-dihydroxyanthraquinone (Dan) and 2-aminofluorene (2-AF) are all products of the Fluka company. Mitomycin C was produced by Zhejiang Haizheng pharmaceutical Co., Ltd, and Cyclophospha was first produced by Shanghai Hualian pharmaceutical Co., Ltd. And (3) self-made male rat liver S9, which is qualified by identification and stored in liquid nitrogen for later use.

1.4 test methods

1.4.1 acute toxicity test (MTD method)

SD rats (body weight 180g-220g)20 in half each. Bw one dose group at 15g/kg. Accurately weighing 90g of the test object, adding distilled water to 240ml of suspension, performing oral gavage for 2 times in an animal fasting state according to 2ml/100g.bw, separating for 4 hours, observing the number of dead animals and general health conditions in two weeks after gavage, and judging the acute toxicity of the test object according to the maximum tolerance.

1.4.2 genotoxicity test

1.4.2.1Ames test A standard plate incorporation test with no rat liver S9 was performed using identified satisfactory strains of TA97, TA98, TAI00 and TAI 02. (S9 mix was used at 0.5 ml/dish). The dosage of the five compositions of the invention is 8, 40, 200, 1000 and 5000 mug/dish (0.5 g of the tested object is accurately weighed in a glass bottle, distilled water is added to 10ml, the highest working concentration is 50mg/ml after fully mixing, the rest concentrations are obtained by diluting with distilled water 5 times, 100 mug of the prepared highest working concentration liquid of the tested object is added to a flat dish to obtain the highest final concentration of 5000 mug/dish, the sample adding amount of the rest concentrations is 100 mug, all the prepared tested objects are sterilized by adopting a 8 pound 15min high pressure mode), and a spontaneous control, a solvent control (sterilized distilled water 100 mug 1/dish) and a positive control are simultaneously set. The positive control without S9 test was 0.2. mu.g/dish of 2,4, 7-trinitro-9-fluorenone (TA97, TA98), 1.5. mu.g/dish of sodium azide TA100), 0.5. mu.g/dish of mitomycin C (TA102), and the positive control with S9 test was 10. mu.g/dish of 2-aminofluorene CTA97, TA98, TA100) and 50. mu.g/dish of 1, 8-dihydroxyanthraquinone (TA 102). Three parallel dishes were made for each test dose and the test was repeated once.

1.4.2.2 marrow pleochromocyte micronucleus test of mice, Kunming mice (weight 25g-30g) are randomly divided into 5 groups, each group has 10 mice, each half of male and female, test groups of the composition of the invention (each group weighs 2.5, 5.0 and 10.0g of test substance, each group adds distilled water to 20ml of suspension), and negative control (distilled water) and positive control (cyclophosphamide 40mg lkg. Animals were gavaged at 0 h and 24 h at 2ml/100g.bw orally, sacrificed 6h after the last exposure, and processed for flaking according to the procedure. Counting 1000 Pleochromocyte (PCE) of each animal, observing the number of the Pleochromocyte (PCE) containing micronucleus, calculating the micronucleus rate (%), simultaneously observing the number of PCE and mature erythrocyte (NCE) in 200 erythrocytes, and calculating the ratio of PCE beta to CE.

1.4.2.3 mouse teratospermia test male mice of Kunming species (weighing 25g-35g) were randomly divided into 5 groups of 5 mice each. Three dose groups of the composition of the present invention (2.5, 5.0 and 10.0g of the test substance, each of which is suspended in 20ml of distilled water) are set as a negative control group (distilled water), a positive control group (cyclophosphamide 40mg/kg. bw) and 2.5, 5.0 and 10.0g/kg. bw, and the animals are orally gazed at 2ml/100g.bw for 5 days. Animals were sacrificed on day 35 after the first gavage, bilateral epididymis were removed and processed according to standard procedures, 1000 intact sperm per animal were observed, and the number of teratospermis was recorded.

1.4.3 rat 30 day feeding test

Weaning SD rats were randomly divided into four groups of 20 rats each, each with half of males and females. The test was carried out with a control group (basal diet) and three test subject dose groups of 2.4, 5.6 and 8.0g/kg.bw (corresponding to 30, 70 and 100 times the recommended intake of the human body, respectively). Because the adding amount of the test substance in the medium and high dose groups exceeds 5 percent in the feed, the protein content in the feed needs to be adjusted, 336g, 784g and 1120g of the test substance and 84g, 196g and 280g of casein are respectively taken from the feed of each dose group, the basic feed is added to 14kg, and the mixture is fully and evenly mixed and processed into pellet feed to feed animals. Animals were fed freely for 30 consecutive days. Animal body weight, feed intake and food remaining amount are weighed once a week, and food intake is calculated, animals are sacrificed 30 days after continuous feeding (fasting before sacrifice for 16 hours), hematology, serum biochemistry and histopathology examination and organ coefficient measurement are performed, week food utilization (%) is calculated according to week weight gain and week food intake, respectively, and total food utilization (%) is calculated at the same time.

1.5 statistics of Experimental data

The mean of each experimental group and the control group is compared by using variance analysis, if the variance is irregular, the rank sum test is used for comparing the sperm distortion rate, and the Poisson distribution method is used for comparing the micronucleus rate. The software used was PEMS3.1 (statistical software package (third edition) of encyclopedia of Chinese medicine medical statistics.

2 results

2.1 acute toxicity test

After oral exposure to a dose of 15g/kg.bw of the composition of the invention, no animal death or obvious toxic symptoms or adverse reactions are observed within two weeks, and the results are shown in table l. That is, the acute oral MTD of the test product to female and male SD rats is more than 15g/kg.

TABLE L oral acute toxicity of the compositions of the invention to SD rats

2.2 genotoxicity test

2.2.1 Ames assay-average colony count per dish for spontaneous controls with and without S9

The average number of the colony retrogradation induced by the positive control group is more than twice of that of the spontaneous control group, and the colony is obviously positive. The average number of the reversion colonies of each dose group and the solvent control group of the composition of the invention does not exceed one time of that of the white hair control group, and the composition shows negative reaction, namely the test sample does not have the function of inducing the test strain to carry out reversion. The results are shown in tables 2 and 3.

2.2.2 mouse marrow pleochromocyte micronucleus test, the proportion of PCE of each dose group of the test object in total red blood cells is not lower than 20 percent of the control value, and the PCE/NCE ratio has no significant difference (P is more than 0.05) compared with the negative control group, which indicates that the sample has no adverse effect on mouse marrow cell proliferation. The Poisson distribution method result shows that the micronucleus rates of the male and female animals in the positive control group are both obviously higher than those in the negative control group (P < O.05), and the micronucleus rates of all groups of the tested substances have no significant difference (P > O.05) compared with those in the negative control group, which indicates that the tested product is a negative result in the micronucleus test of the bone marrow cells of the mice. The results are shown in Table 4.

2.2.3 mouse sperm malformation test, the rank and test result shows that the sperm malformation rate of the positive control group is obviously higher than that of the negative control group (P < O.05), and the sperm malformation rate of each dosage group of the composition has no obvious difference (P >0.05) compared with that of the negative control group, which indicates that the test article is a negative result in the mouse sperm malformation test. The results are shown in Table 5.

2.3 rat 30 day feeding test

During the period of feeding 30 days, animals in the control group and the 3 dose groups have normal food intake, water drinking, excrement and urine, good growth and development conditions and general performance, and no obvious behavior change and toxic performance are observed.

2.3.1 Effect on body weight and food availability the animals in each dose group of the test substances had no significant difference in weekly food intake, weekly weight gain, weekly food availability and total food availability compared with the control group (P > 0.05). Indicating that the test article has no adverse effect on body weight and food availability. The results are shown in tables 6 and 7.

2.3.2 organ coefficient measurement results Table 8 shows the weight of the important organ and organ coefficient (wet organ weight/fasting body weight) of each dose group of the test substances. As can be seen from the table, the weight and organ coefficient of the important organs in each dose group were not significantly different from those in the control group (P > O.05).

2.3.3 end-stage hematological test results Table 9 shows the results of the measurement of the conventional hematological indices (erythrocytes, hemoglobin, leukocytes and classification) at the end of the test. As can be seen from the table, the White Blood Cell (WBC) count was significantly higher in the female-only high dose group than the control group (P < o.05), but the variation was within the historical control range of the laboratory and was not biologically significant. The measured indexes of female and male mice of other dose groups of the test object have no significant difference compared with the control group (P > O.05).

2.3.4 end Biochemical index test results Table 10 shows that glutamic-oxaloacetic transaminase (AST) and myo-snore (CREA) in the male mice low dose group are significantly higher than the control group (P < O.05), and CREA in the female mice medium dose group is significantly lower than the control group (P < O.05), but the changes are within the historical control range of the laboratory and have no biological significance. Compared with the control group, the biochemical indexes of the test object, such as liver function, kidney function, blood fat, blood sugar and the like of the female and male mice of each dosage group have no significant difference (P is more than O.05).

2.3.5 histological examination results gross examination of the experimental animals at the end of the experiment was performed. Gross examination revealed no significant lesions, and therefore histological examination was performed only on liver, kidney, stomach, jejunum, spleen innocent pills and ovary in the high dose and control groups. The results of histological examination are shown in tables 11-17, and only individual animals tested were found to have liver tissue leucocytes, renal calcium deposits and chronic renmontitis. The leucocyte focus of the liver tissue is shown as a small amount of sporadic focal change and is positioned in the portal area or the hepatic lobule, the focus is composed of mononuclear cells, the deposition of renal calcium salt is shown as the junction of the medullary inner and outer striae and the blue granular substance in individual renal tubules, and the chronic renmenitis is shown as the hyperplasia of the renal menamantia and the infiltration of the mononuclear cells with the epithelial cells as the main part. However, the number of all the pathological cases in the high-dose group has no significant difference compared with the control group, which indicates that the pathological changes are unrelated to the tested substances and belong to the spontaneous pathological changes of animals. In conclusion, no lesion change caused by the test substance was observed in the organs of the animals in each dose group.

The examination results of the biological indexes show that in a feeding test of a rat for 30 days, the highest dosage is 100 times of the recommended human intake, and the composition does not cause abnormal changes of important indexes of the rat, such as the overall health condition, physiological and biochemical functions, organ tissue morphology and the like, so that the maximum non-effective dosage of the product is preliminarily estimated to be more than 8.0g/kg.bw (100 times of the recommended human intake).

TABLE 2 results of Ames experiments on compositions according to the invention (first time)

TABLE 3 results of Ames test for compositions of the invention (second)

TABLE 4 Effect of the compositions of the present invention on the incidence of bone marrow nuclei in mice

TABLE 5 mouse teratospermia test results for compositions of the invention

TABLE 6 Effect of the compositions of the invention on rat body weight

TABLE 7 Effect of the compositions of the present invention on food availability in rats

TABLE 8 Effect of the compositions of the invention on weight and coefficient of the rat viscera

TABLE 9 Effect of the compositions of the invention on the hematological indices of rats

TABLE 10 Effect of the compositions of the invention on Biochemical indicators of serum in rats

TABLE 11 histological observation of livers of 30-day feeding test of the compositions of the invention

TABLE 12 study of jejunal histology by 30-day feeding test of the composition of the invention

TABLE 13 study of renal histology observations of a 30 day feeding trial of a composition of the invention

TABLE 14 histological observations of spleens from 30-day feeding trials of compositions of the invention

TABLE 15 ovarian histological observations of the 30-day feeding trial of the compositions of the invention

TABLE 16 testis histology observations from 30 day feeding trials of compositions of the invention

TABLE 17 histological observations of the stomach of the 30-day feeding trial of the compositions of the invention

The examination results of the biological indexes show that in a feeding test of a rat for 30 days, the highest dosage is 100 times of the recommended human intake, and the composition does not cause abnormal changes of important indexes of the rat, such as the overall health condition, physiological and biochemical functions, organ tissue morphology and the like, so that the maximum non-effective dosage of the product is preliminarily estimated to be more than 8.0g/kg.bw (100 times of the recommended human intake).

3 small knot

The composition of the invention has acute oral MTD of more than 15g/kg.bw for rats, and belongs to nontoxic class. The three genotoxicity tests, namely the Ames test, the mouse bone marrow cell micronucleus test and the mouse teratospermia test, are negative results. No abnormal change of animal health condition, biochemical, hematological indexes and organ tissue morphology is seen in the rat feeding test for 30 days, and the maximum non-effect dose of the product is estimated to be more than 8.0g/kg.bw (100 times of the recommended intake of human body) preliminarily.

II, throat clearing animal function test:

the composition of the invention is subjected to throat clearing animal function tests by analysis and evaluation center of western public health college entrusted to Sichuan university, and the test results show that:

the test was carried out 30 days after oral administration of the compositions of the present invention to mice (Balb/c) at doses of 0.8g/kg.bw, 1.6g/kg.bw and 2.4g/kg.bw (corresponding to 10, 20 and 30 times the recommended daily dose for the recommended daily administration by the examiner, respectively), SD rats at doses of O.4g/kg.bw, 0.8g/kg.bw and 1.6g/kg.bw (corresponding to 5, 10 and 20 times the recommended daily dose for the examiner, respectively). In the mouse ear swelling test, the auricle swelling rate of the 2.4g/kg.bw dose group is obviously reduced compared with that of the control group mouse. In a rat cotton ball implantation test, the net amount of granuloma is obviously reduced in a 1.6g/kg.bw dosage group compared with a control group; in a rat foot toe swelling test, the volume swelling rate of the toes after 1h is obviously reduced in a 0.8g/kg.bw dosage group compared with a control group. The throat clearing function test of the test product can be regarded as a positive result according to the evaluation standard.

1 materials and methods

1.1 the composition of the present invention is provided by Shijiazhuang Ling pharmaceutical industries, Inc., and the recommended daily dose for the censorship is 4.8 g/person/day.

1.2 test animals

SPF grade male Ba1b/c mice weighing 18-22 g. Supplied by Woodso Biotechnology Inc. (license number: SCXK (Chuan) 2013-24). The animals were bred using a barrier-grade animal house (license number: Sichuan Experimental animal management Committee SYXK (Sichuan) 2013-. The drinking water is pure water, and in the whole test process, animals freely eat the drinking water at the room temperature of 20-24 ℃ and the relative humidity of 45-65%.

SPF grade male SD rats weighing 180-220 g. Supplied by Woodso Biotechnology Inc. (license number: SCXK (Chuan) 2013-24). The animals were bred using a barrier-grade animal house (license number: Sichuan Experimental animal management Committee SYXK (Sichuan) 2013-. The drinking water is pure water, and in the whole test process, animals freely eat the drinking water at the room temperature of 20-24 ℃ and the relative humidity of 45-65%.

1.3 dose selection

After the mice are purchased and fed with the basic feed, the mice are divided into a 0.8g/kg.bw group, a 1.6g/kg.bw group and a 2.4g/kg.bw group (which are respectively equal to 10 times, 20 times and 30 times of the recommended daily dose for the censorship) and a control group according to a random grouping principle, and each group contains 12 mice. The experimental group was gavage with a corresponding amount of sample (12 g of the sample to be tested was weighed, a small amount of sterilized deionized water was added and milled thoroughly, and then sterilized deionized water was added to 100 mL and mixed thoroughly as a high-dose group gavage solution, i.e., a medium-dose group gavage solution was obtained by mixing l parts of sterilized water and 2 parts of a high-dose group gavage solution, and a low-dose group gavage solution was obtained by diluting medium-dose group gavage solution doubly with sterilized water and mixing uniformly), and the control group was gavage with sterilized water at a gavage amount of 20mL/kg.bw once a day for 30 days continuously. After the rats are purchased and fed with basal feed, the rats are divided into 24 rats per group according to the random grouping principle, wherein the rats are divided into O.4g/kg. bw, 0.8g/kg. bw and 1.6g/kg. bw dosage groups (which are respectively equal to 5 times, 10 times and 20 times of recommended daily dose of the censorship) and control groups. The experimental group was filled with samples of the corresponding doses (weighing 16g of the sample to be tested, adding a small amount of sterilized deionized water, grinding thoroughly, adding sterilized deionized water to 100 hours, mixing thoroughly to obtain a high dose group of gastric lavage fluid, mixing l of sterilized water and 2 parts of high dose group of gastric lavage fluid to obtain a medium dose group of gastric lavage fluid, diluting medium dose group of gastric lavage fluid doubly with sterilized water, mixing well to obtain a low dose group of gastric lavage fluid), and the control group was filled with sterilized water to obtain a gastric lavage amount of 1Oml/kg.bw, and the gavage was continued for 30 days once a day.

1.4 Main instruments and reagents

1.4.1 Primary Instrument BSA224S electronic balance; siderelis, Germany; toe volume measuring instrument; chengduta alliance technologies, Inc.; a 9mm diameter punch, and the like.

1.4.2 Main reagents dextran 4 ten thousand, Shanghai future industry Co., Ltd, xylene Renjin chemical Co., Tianjin City.

1.5 Experimental methods

1.5.1 weight measurement, continuously gavage for 30 days, and weighing the weight of the animals on the 1 st, 8 th, 15 th, 23 th and 30 th days of gavage.

1.5.2 mouse ear swelling test on day 30 of continuous gavage, 20 μ 1 of xylene was taken, dropped in the center of auricle on the lateral side of the right ear of mouse to allow free diffusion, after 30 minutes, the mouse was euthanized, both ears were cut off, ear pieces were punched at the same positions of both ears with a 9mm diameter punch and weighed, and the auricle swelling rate was calculated by taking the difference between the weights of both ears as the auricle swelling value. Compared with the control group, the test group has the advantages that the auricle swelling rate is obviously reduced, the difference is significant, and the test sample mouse ear swelling test result can be judged to be positive.

Auricle swelling rate (%) = auricle swelling value/control ear weight x 100%

1.5.3 rat Cotton ball implantation test, which is to prepare about 20-25mg compact cotton balls from absorbent cotton, put the cotton balls into a constant temperature drying oven for drying at 60 ℃ for 3h after autoclaving, take out the cotton balls to weigh under aseptic condition, dry and store for later use. 8 days before the experiment, the hair at the groin at both sides of the rat is removed by a depilator, the rat is lightly anesthetized by ether, sterilized by iodophor, the groin skin at both sides of the rat is cut under aseptic conditions, a cotton ball for standby is implanted, the incision is sutured, and the test substance is continuously given. On the day of experiment, after giving the test substance for l hours, the rats were euthanized, the skin was cut at the original suture, the cotton ball granulation tissue was peeled and taken out, placed in a weighed clean plate, dried for l hours in a constant temperature drying oven with a lid opened at 60 ℃, and weighed, and the net granulomatous amount was calculated.

Compared with a blank control group, the experimental group has the advantages that the net quantity of granuloma is obviously reduced, the difference is significant through statistical treatment, and the positive result of the cotton ball implantation experiment of the rat of the test sample can be judged.

Granuloma absolute amount (mg) = weight of granuloma of cotton ball after drying-weight of raw cotton ball

1.5.4 toe swelling test in rats, the test specimen was administered once by gavage on the day of completion of the test, and 1 hour later, the volume of the right hind toe of each group of rats was measured with a toe volume meter as 0 hour toe volume. Then, 4 thousands of 0.1mL of dextran with the concentration of 1% prepared by injecting sterile steam room water into the subcutaneous part of the right hind toe of the rat, measuring the volume of the toe of the rat in l, 2,4 and 6 hours respectively, measuring the same part for 3 times, and taking an average value. And calculating the toe swelling rate of each time period by taking the difference between the toe volume measured at different time periods and the toe volume before the action of the inflammatory agent as a swelling value. Compared with the control group, the experimental group has the advantages that the toe volume swelling rate is obviously reduced before and after any time point stimulation, the difference is significant, and the positive toe swelling experimental result of the rat with the test sample can be judged.

Swelling rate (%) = swelling value/pro-inflammatory toe volume x 100%

1.6 statistics of Experimental data

Data were processed using analysis of variance with mean comparisons between experimental and control groups. The software used is statistical software package (PEMS3.1, university of Sichuan China public health statistics textbook and research laboratory) from encyclopedia of Chinese medicine medical statistics.

2 results

2.1 Effect of the compositions of the invention on body weight

2.1.1 mice ear swelling group by analysis of variance, there was no significant difference in initial body weight, intermediate body weight, end body weight, and body weight gain value (P >0.05) in each dose group compared to the control group, see Table l 8.

TABLE 18 double body sounds of the compositions of the invention on mouse ear swelling

2.1.2 rats in the cotton ball implantation group, the initial weight, the middle weight, the end weight and the weight gain value of each dose group were not significantly different from those of the control group by analysis of variance (P >0.05), as shown in Table 19.

TABLE 19 Effect of the compositions of the present invention on the body weight of rat tampon-implanted groups

2.1.3 the toe swelling groups of rats were analyzed by variance, and there was no significant difference in initial body weight, middle body weight, end body weight, and body weight gain (P >0.05) in each dose group compared with the control group, as shown in Table 20.

TABLE 20 Effect of the compositions of the present invention on body weight in the toe swelling group of rats

2.2 Effect of the composition of the present invention on the swelling Rate of auricles in mice

Through analysis of variance, compared with control mice, the auricle swelling rate of the test object is not significantly reduced in 0.8g/kg.bw and 1.6g/kg.bw dose groups (P > O.O5), and the auricle swelling rate of the 2.4g/kg.bw dose group is significantly reduced (P < O.Ol) in each dose group, respectively, see Table 21.

TABLE 21 Effect of the compositions of the present invention on the rate of swelling of mouse auricles

2.3 Effect of the compositions of the invention on the Net amount of granuloma in rats

The o.4g/kg.bw and 0.8g/kg.bw dose groups showed no significant difference in net granuloma (P > o.o5) compared to the control group rats, and the 1.6g/kg.bw dose group showed a significant decrease in net granuloma (P < o.o5) compared to the control group rats, as shown in table 22.

TABLE 22 Effect of the compositions of the present invention on the net amount of granuloma in rats

2.4 Effect of the composition of the present invention on the swelling Rate of the toes of rats

Through analysis of variance, compared with a control group, each dose group has no difference (P > O.OS) in the swelling rate of 2h, 4h and 6h, and in the measurement of the swelling rate of 1h, the dose group of 0.8g/kg.bw is obviously lower than that of the control group (P <0.05), and the other two dose groups have no significant difference (P > O.O5) with the control group, which is shown in Table 23.

TABLE 23 Effect of the compositions of the present invention on the rate of swelling of the toes of rats

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The composition of the invention has no adverse effect on body weight and weight gain after oral administration of 0.8g/kg.bw, 1.6g/kg.bw and 2.4glkg.bw to mice (Balb/c) after 30 days, and has no adverse effect on body weight and weight gain after oral administration of O.4g/kg.bw, 0.8g/kg.bw and 1.6g/kg.bw to SD rats after 30 days. In the mouse ear swelling test, the auricle swelling rate of the 2.4g/kg.bw dose group is obviously reduced compared with that of the control group mice (P < 0.01). The net amount of granuloma was significantly reduced in the 1.6g/kg.bw dose group compared to the control group in the rat tampon implantation test (P <0.05), and the volume swelling rate of lh toes was significantly reduced in the 0.8g/kg.bw dose group compared to the control group in the rat toe swelling test (P < 0.05). The test article can be considered as a positive result in the throat clearing function test of the animal experiment according to the evaluation standard.

Thirdly, the composition of the invention has the function of clearing heat from throat and tests on human body

In order to verify the throat-clearing function of the composition, a throat-clearing function human body test is performed in the subsidiary hospital of western medicine university, and the test results are as follows: 101 test subjects meeting the requirements are randomly divided into a test group and a control group, and the effective number of the test subjects is 100, 50 test subjects are in the test group, and 50 control subjects are in the control group. After the composition is taken by a test group for 30 days according to requirements (a control group is a blank control), the main clinical symptom and sign improvement rate of the test group are respectively 18.00% and 84.00%, the main clinical symptom and sign improvement rate of the control group are respectively 0.06% and 38.00%, the main clinical symptom and sign improvement rate of the test group and the control group have significant difference (P <0.05) when the test group and the test group are compared, the main clinical symptom score and the sign score of the test group after test eating are reduced, and the difference has statistical significance (P <0.05) when the test group and the control group before test eating and after test eating are compared. The blood routine, urine routine, stool routine and blood biochemical index of the two groups before and after the test eating are all in the normal range, and no allergy or other adverse reactions are seen during the test eating. The product has no adverse effect on the physical health of the subject.

According to the judgment standard of a throat-clearing function evaluation method (national food and drug administration [2012] 107), the composition has the function of clearing throat.

1 materials and methods

1.1 sample

The sample is the composition of the present invention and is provided by Shijia, Ling medicine, Inc., and produced by Shijia, Ling medicine, Inc. The sample properties are brown to tan tablets, 0.8 g/tablet and 18 tablets/bag, and the sample quantity is 600 bags. Batch number 140701. The storage method comprises sealing, placing in dry place, and keeping shelf life of 24 months. The recommended dose for human body is 3 times daily, 2 tablets each time, namely the dose is 4.8 g/day.

1.2 test subjects

101 subjects were selected on a voluntary basis.

1.2.1 subject inclusion criteria

A volunteer subject examined to meet at least one of the following 1.2.1.1 and 1.2.1.1.2.

1.2.1.1 physical signs of chronic pharyngitis, and subjective symptoms of pharyngalgia, pharynx itch, dry throat, dry cough, foreign body sensation, and aggravation of speaking.

1.2.1.2 pharyngeal symptoms of pharyngeal mucosa edema, mucosal congestion, pharyngeal posterior wall lymphoid follicle hyperplasia, and secretion attachment.

1.2.2 subject exclusion criteria

None of the following were included in this test.

1.2.2.1 acute stage of chronic pharyngitis or acute pharyngitis, vocal nodule, common cold or smoking factor.

1.2.2.2 nasopharyngeal, pharyngeal, laryngeal, nasal, laryngeal, esophageal, cervical and tuberculosis, and metastatic lung cancer.

1.1.2.3 people under 18 years of age or over 65 years of age, baby and lactating women and people allergic to the test product.

1.2.2.4 patients with serious diseases of heart, brain, blood vessel, liver, kidney, hemopoietic system, bronchus and lung, mental disease and sleep disease.

1.2.2.5 taking articles related to the tested function in a short time affects the judgers of the results.

1.2.2.6 if the tested sample is not taken or other medicines are added during the administration, the efficacy or data are not judged to be insufficient.

1.3 Experimental design and grouping

Two control designs, self and group, were used. The test group and the control group are randomly divided according to pharyngeal symptoms and signs of the subjects. And (3) performing balance test by considering main factors influencing results such as disease course, age, gender and the like as much as possible during grouping so as to ensure comparability among groups. The effective number of the subjects in each group is not less than 50.

1.4 dosage and time

The test group takes the composition of the invention according to the recommendation, and takes the composition orally, 3 times a day, 2 tablets each time. The control group is blank control, i.e. the control group is not specially required. The subject is administered for 30 consecutive days. The subjects did not change the original eating habits and normal diet during the test eating period, and did not take the drugs or other health foods related to the function of clearing heat from throat.

1.5 Main instruments, reagents and test environmental requirements

Hitachi 7180 full-automatic biochemical analyzer (Hitachi, Japan Co., Ltd.), DIRUI H-300 urine eight-item analyzer (Changchun Borui Co., Ltd.), SysmexN-I0 [ B2] Tri-component blood analyzer CSysmex Co., Ltd.), Sysmex blood cell analysis diluent (Sysmex Co., Ltd.), KX-21 full-automatic blood analyzer (Hisenmeikang Co., Japan), BS-800 full-automatic biochemical analyzer (Shenzhen Meyer Co., Ltd.), DIRUI urine analysis reagent strip (Changchun Di Co., Ltd.), and Lidman biochemical kit (Beijing Lidman Biochemical Co., Ltd.).

1.6 Observation index

1.6.1 general conditions

Including mental, sleep, diet, stool and urine, heart rate, blood pressure, etc.

1.6.2 Security observations

1.6.2.1 routine examinations of blood, urine, stool, erythrocyte count, hemoglobin, leukocyte count, platelet count, urine routine, stool microscopic examination, etc.

1.6.2.2 examination of liver and kidney function, serum Albumin (ALB), Total Protein (TP), liver and kidney function (glutamic-oxaloacetic transaminase (AST), alanine Aminotransferase (ALT), urea nitrogen (BUN), myo-inositol (CRE), blood sugar (GLU), blood lipid (total cholesterol (TC), and Triglyceride (TG).

1.6.2.3 chest X-ray, electrocardiogram and B-ultrasound in abdomen, which are examined once before eating trial.

1.6.3 Observation of efficacy

1.6.3.1 Observation of clinical symptoms

Accurately recording pharyngeal subjective symptoms before and after test feeding of a subject, wherein the main pharyngeal symptoms comprise pharyngalgia, pharyngeal itching, dry pharynx, dry cough, excessive foreign body sensation aggravation and the like, calculating integral (l degree-1 point, 2 degree-2 points and 3 degree-3 points) according to the weight of symptoms, and counting the integral change and symptom improvement rate.

1.6.3.2 Observation of body signs

All subjects performed pharyngeal examination before and at the end of the test, which was marked by pharyngeal mucosal congestion, mucosal edema, pharyngeal wall lymphoid follicle hyperplasia, secretions, and the like. And respectively recording the change of the physical signs before and after the test feeding according to the grade I, II and III of the light, medium and heavy weight of the examination result, and calculating the physical sign integral and the improvement rate.

1.6.3.3 determination of efficacy

The medicine has the effects of relieving the symptom of I degree and relieving the pharyngeal physical sign examination result of I level.

No obvious change in symptoms and signs.

1.7 statistical analysis of data

The metrology data is analyzed using a t-test. The self-control adopts paired t test, and the two-group mean comparison adopts two-sample t test. And (3) carrying out proper variable conversion on the data with non-normal distribution or uneven variance, carrying out t test on the converted data after the converted data meets the normal variance, and carrying out the sum-of-rank test if the converted data still can not meet the requirement of the normal variance.

The improvement rate is the counting data, x is adopted²And (6) checking.

1.8 determination of results

Compared with the test group before and after the test and the control group after the test, the pharyngeal clinical symptom integral and the sign integral are obviously reduced, the symptom sign improvement rate is obviously increased compared with the control group, and the statistical treatment difference has significance, so that the tested sample can be judged to have the function of clearing heat from throat.

2 results

2.1 general conditions

The test included 101 subjects, and the subjects were randomly divided into a test diet group and a control group, 51 test diet groups and 50 control groups. During the test period, one sample of the test group is lost, so that 50 samples of the effective subjects are taken as the test group and 50 samples of the control group, and the total number of the effective subjects is 100. The subjects had normal blood routine, urine routine, stool routine, liver and kidney function, chest X-ray, electrocardiogram and type-B ultrasonic examination before the test. The age, sex, course and main clinical symptom of the patients in the two groups before the test feeding are not obviously different (P is more than 0.05). The general condition comparison before the test is shown in Table 24.

TABLE 24 general Pre-test comparisons

2.2 Effect on efficacy index

2.2.1 symptom score and rate of improvement of clinical symptoms

A comparison of the scores of clinical symptoms before and after the test, both between self and group is shown in Table 25. The clinical symptom scores of the test group and the control group before the test are not significantly different (P >0.05), and the clinical symptom scores of the control group before and after the test are not statistically different (P > 0.05). Compared with a control group, the main clinical symptom score is remarkably reduced (P is less than 0.05) in the pre-and post-test self comparison of the test group and the test group. The total improvement rate of clinical symptoms of the test group and the control group after the test feeding is respectively 0.06 percent and 18.00 percent, and the improvement rate of the test feeding group is obviously higher than that of the control group (P < 0.05). The results are shown in Table 26.

Table 25 major clinical symptom integral change (integral value,

s）

TABLE 26 improvement of clinical symptoms

2.2.2 sign integration and Rate of improvement of signs

The results of the sign integration are analyzed in table 27. The body mark of the test group after the test eating is obviously reduced, and the difference is significant compared with the control group before the test eating and after the test eating (P is less than 0.05). The total improvement rates of main physical signs of the control group and the test group before and after the test are respectively 38.00 percent and 84.00 percent, and the improvement rate of the test group is obviously higher than that of the control group (P < 0.05). The results are shown in Table 28.

Table 27 volume integration change (integrated value,

s）

TABLE 28 improvement of the main signs

2.3 Effect on human safety metrics

The test taker has no adverse reaction and anaphylactic reaction during the test eating period, and has no obvious changes in spirit, sleep, diet, stool and urine, etc. The blood routine, urine routine, stool routine and blood biochemical index detection results before and after the test are shown in Table 29. All indexes before and after the test are in a normal range.

TABLE 29 test results of blood, urine, stool routine and blood biochemical index before and after meal test: (

s）

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101 test subjects meeting the requirements are randomly divided into a test group and a control group, and the effective number of the test subjects is 100, 50 test subjects are in the test group, and 50 control subjects are in the control group. The control group is blank control after the test group takes the composition of the invention for 30 days according to requirements). The main clinical symptom and sign improvement rate of the test group are respectively 18.00 percent and 84.00 percent, the main clinical symptom and sign improvement rate of the control group are respectively 0.06 percent and 38.00 percent, the comparison between the groups shows that the main clinical symptom and sign improvement rate have significant difference (P <0.05), the main clinical symptom score and sign score after the test eating of the test eating group are reduced, and the difference has statistical significance (P <0.05) compared with the control group before the self test and after the test eating, which indicates that the composition has the function of clearing heat from throat. The blood routine, urine routine, stool routine and blood biochemical index of the two groups before and after the test eating are all in the normal range, and no allergy or other adverse reactions are seen during the test eating. The product has no adverse effect on the health of the subject. The composition of the present invention has a function of clearing heat from the throat according to the judgment criteria of the method for evaluating the function of clearing heat from the throat (national food and drug administration [2012] 107).

Detailed Description

Example 1:

360g of honeysuckle; figwort root 360 g; 300g of Chinese olive; 180g of platycodon grandiflorum; 180g of emblic leafflower fruit; 30g of momordica grosvenori; menthol 1.2 g.

(1) And (3) crushing menthol: weighing menthol, crushing, and sieving with a 100-mesh sieve for later use;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction twice, 1 hour each time, adding 12 times of water for the first time, adding 10 times of water for the second time, and filtering the extract for later use:

(3) concentration: concentrating the extracting solution under reduced pressure (the temperature is 60-80 ℃, the vacuum degree is 0.04-0.08 MPa) to obtain clear paste with the relative density of 1.08-1.12 (60 ℃); adding a proper amount of ethanol into the clear paste to ensure that the ethanol content is 70%, uniformly stirring, and standing for 48 hours at the temperature of 2-10 ℃; filtering, taking the filtrate, recovering ethanol under reduced pressure, and concentrating (at the temperature of 60-80 ℃ and the vacuum degree of 0.04-0.08 MPa) into thick paste with the relative density of 1.20-1.30 (at 60 ℃);

(4) and (3) drying: drying by adopting a vacuum belt type, wherein the temperature of a heating plate is 110-120 ℃, the vacuum degree is 0.08-0.10 MPa, and collecting dry paste for later use;

(5) crushing: pulverizing the dry extract obtained by vacuum belt drying, and sieving with 100 mesh sieve;

(6) and (3) granulating: putting the dry paste powder into a mixer, adding 300g of lactose, 164g of dextrin and 60g of erythritol, uniformly mixing, adding 80-90% ethanol to prepare a soft material, granulating by using a 16-mesh sieve, and drying at the temperature of below 60 ℃ to obtain the dry paste;

(7) straightening: putting the dried granules into a crushing and granulating machine, and granulating by using a conical sieve with the diameter of 1.5 mm;

(8) total mixing: adding 4g of menthol powder, 4g of magnesium stearate and 0.4g of sucralose into the granules after finishing the granules, uniformly mixing in a mixer for 8 revolutions per minute, and mixing for 20 minutes;

(9) tabletting: tabletting, and controlling the weight of each tablet to be 0.8 g.

Example 2:

300g of honeysuckle; 420g of radix scrophulariae; 250g of Chinese olive; 210g of platycodon grandiflorum; 150g of emblic leafflower fruit; 35g of momordica grosvenori; 1g of menthol.

(1) And (3) crushing menthol: weighing menthol, crushing, and sieving with a 100-mesh sieve for later use;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction twice, 1 hour each time, adding 12 times of water for the first time, adding 10 times of water for the second time, and filtering the extract for later use:

(3) concentration: concentrating the extracting solution under reduced pressure at the temperature of 60 ℃ and the vacuum degree of 0.04-0.08 MPa to form clear paste with the relative density of 1.08-1.12; adding a proper amount of ethanol into the clear paste to ensure that the ethanol content is 70%, uniformly stirring, and standing for 48 hours at the temperature of 2-10 ℃; filtering, taking the filtrate, recovering ethanol under reduced pressure, and concentrating at 60-80 ℃ and 0.04-0.08 MPa to obtain thick paste with the relative density of 1.20-1.30;

(4) and (3) drying: drying by adopting a vacuum belt type, wherein the temperature of a heating plate is 110-120 ℃, the vacuum degree is 0.08-0.10 MPa, and collecting dry paste for later use;

(5) crushing: pulverizing the dry extract obtained by vacuum belt drying, and sieving with 100 mesh sieve;

(6) and (3) granulating: putting the dry paste powder into a mixer, adding 295g of lactose, 160g of dextrin and 65g of erythritol, uniformly mixing, adding 80-90% ethanol to prepare a soft material, granulating by using a 16-mesh sieve, and drying at the temperature of below 60 ℃ to obtain the dry paste;

(7) straightening: putting the dried granules into a crushing and granulating machine, and granulating by using a conical sieve with the diameter of 1.5 mm;

(8) total mixing: adding 5g of menthol powder, 5g of magnesium stearate and 0.5g of sucralose into the granules after finishing the granules, uniformly mixing in a mixer for 8 revolutions per minute, and mixing for 20 minutes;

(9) encapsulating by conventional method, and controlling the weight of the granule to 0.8 g.

Example 3:

420g of honeysuckle; 300g of figwort; 350g of Chinese olive; 150g of platycodon grandiflorum; 210g of emblic leafflower fruit; 25g of momordica grosvenori; menthol 1.4 g.

(1) And (3) crushing menthol: weighing menthol, crushing, and sieving with a 100-mesh sieve for later use;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction twice, 1 hour each time, adding 12 times of water for the first time, adding 10 times of water for the second time, and filtering the extract for later use:

(3) concentration: concentrating the extracting solution under reduced pressure (the temperature is 60-80 ℃, the vacuum degree is 0.04-0.08 MPa) to obtain clear paste with the relative density of 1.08-1.12 (60 ℃); adding a proper amount of ethanol into the clear paste to ensure that the ethanol content is 70%, uniformly stirring, and standing for 48 hours at the temperature of 2-10 ℃; filtering, taking the filtrate, recovering ethanol under reduced pressure, and concentrating (at the temperature of 60-80 ℃ and the vacuum degree of 0.04-0.08 MPa) into thick paste with the relative density of 1.20-1.30 (at 60 ℃);

(4) and (3) drying: drying by adopting a vacuum belt type, wherein the temperature of a heating plate is 110-120 ℃, the vacuum degree is 0.08-0.10 MPa, and collecting dry paste for later use;

(5) crushing: pulverizing the dry extract obtained by vacuum belt drying, and sieving with 100 mesh sieve;

(6) and (3) granulating: putting the dry paste powder into a mixer, adding 250g of lactose, 180g of dextrin and 65g of erythritol, uniformly mixing, adding 80-90% ethanol to prepare a soft material, granulating by using a 16-mesh sieve, and drying at the temperature of below 60 ℃ to obtain the dry paste;

(7) straightening: putting the dried granules into a crushing and granulating machine, and granulating by using a conical sieve with the diameter of 1.5 mm;

(8) total mixing: adding menthol powder, 3g of magnesium stearate and 0.6g of sucralose into the granules after finishing the granules, uniformly mixing in a mixer, and mixing for 20 minutes at 8 revolutions per minute;

(9) bagging to obtain powder.

Example 4: the preparation of the medicinal pill of the invention comprises the following steps:

350g of honeysuckle; 350g of figwort; 280g of Chinese olive; 175g of platycodon grandiflorum; 175g of emblic leafflower fruit; 22g of momordica grosvenori; menthol 1.1 g.

The preparation method of the medicinal and edible traditional Chinese medicine composition tablet comprises the following steps:

(1) and (3) crushing menthol: weighing menthol, crushing, and sieving with a 100-mesh sieve for later use;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction twice, 1 hour each time, adding 12 times of water for the first time, adding 10 times of water for the second time, and filtering the extract for later use:

(3) concentration: concentrating the extracting solution under reduced pressure (the temperature is 60-80 ℃, the vacuum degree is 0.04-0.08 MPa) to obtain clear paste with the relative density of 1.08-1.12 (60 ℃); adding a proper amount of ethanol into the clear paste to ensure that the ethanol content is 70%, uniformly stirring, and standing for 48 hours at the temperature of 2-10 ℃; filtering, taking the filtrate, recovering ethanol under reduced pressure, and concentrating (at the temperature of 60-80 ℃ and the vacuum degree of 0.04-0.08 MPa) into thick paste with the relative density of 1.20-1.30 (at 60 ℃);

(4) and (3) drying: drying by adopting a vacuum belt type, wherein the temperature of a heating plate is 110-120 ℃, the vacuum degree is 0.08-0.10 MPa, and collecting dry paste for later use;

(5) crushing: pulverizing the dry extract obtained by vacuum belt drying, and sieving with 100 mesh sieve;

(6) and (3) granulating: putting the dry paste powder into a mixer, adding 290g of lactose, 150g of dextrin and 55g of erythritol, uniformly mixing, adding 80-90% ethanol to prepare a soft material, granulating by using a 16-mesh sieve, and drying at the temperature of below 60 ℃ to obtain the dry paste;

(7) straightening: putting the dried granules into a crushing and granulating machine, and granulating by using a conical sieve with the diameter of 1.5 mm;

(8) total mixing: adding menthol powder, 3.5g of magnesium stearate and 0.3g of sucralose into the granules after finishing the granules, uniformly mixing in a mixer for 8 r/min, and mixing for 20 minutes;

(9) making into pill by conventional method.

Claims (9)

1. A medicine-food homologous traditional Chinese medicine composition with the health-care functions of clearing and moistening the throat is characterized by being prepared from the following raw material medicines in parts by weight:

30-42 parts of honeysuckle; 30-42 parts of radix scrophulariae; 25-35 parts of Chinese olive; 15-21 parts of platycodon grandiflorum; 15-21 parts of emblic leafflower fruit; 2.5-3.5 parts of momordica grosvenori; 0.1-0.14 part of menthol.

2. The medicine-food homologous traditional Chinese medicine composition as claimed in claim 1, which is characterized by being prepared from the following raw material medicines in parts by weight:

30 parts of honeysuckle; 42 parts of radix scrophulariae; 25 parts of Chinese olive; 21 parts of platycodon grandiflorum; 15 parts of emblic leafflower fruit; 3.5 parts of momordica grosvenori; 0.1 part of menthol.

3. The medicine-food homologous traditional Chinese medicine composition as claimed in claim 1, which is characterized by being prepared from the following raw material medicines in parts by weight:

42 parts of honeysuckle; 30 parts of radix scrophulariae; 35 parts of Chinese olive; 15 parts of platycodon grandiflorum; 21 parts of emblic leafflower fruit; 2.5 parts of momordica grosvenori; 0.14 part of menthol.

4. The medicine-food homologous traditional Chinese medicine composition as claimed in claim 1, which is characterized by being prepared from the following raw material medicines in parts by weight:

36 parts of honeysuckle; 36 parts of radix scrophulariae; 30 parts of Chinese olive; 18 parts of platycodon grandiflorum; 18 parts of emblic leafflower fruit; 3 parts of momordica grosvenori; 0.12 part of menthol.

5. The medicine-food homologous traditional Chinese medicine composition as claimed in claim 1, which is characterized by being prepared from the following raw material medicines in parts by weight:

35 parts of honeysuckle; 35 parts of radix scrophulariae; 28 parts of Chinese olive; 17.5 parts of platycodon grandiflorum; 17.5 parts of emblic leafflower fruit; 2.2 parts of momordica grosvenori; 0.11 part of menthol.

6. The medicinal and edible traditional Chinese medicine composition as claimed in any one of claims 1 to 5, wherein the preparation of the active ingredients comprises the following steps:

(1) pulverizing Mentholum;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction, and filtering an extracting solution for later use:

(3) concentration: concentrating the extractive solution to obtain fluid extract; precipitating, filtering, collecting filtrate, recovering ethanol, and concentrating to obtain soft extract;

(4) and (3) drying: drying the thick paste obtained in the step (3) to obtain dry paste for later use;

(5) crushing: and (4) crushing the dry paste obtained in the step (4) to obtain the active component of the traditional Chinese medicine composition.

7. The medicinal and edible traditional Chinese medicine composition as claimed in any one of claims 1-6, characterized in that the preparation formulation of the traditional Chinese medicine composition is capsule, tablet, pill, powder, soft capsule or paste.

8. The Chinese medicinal composition as claimed in claim 7, which is used as both medicine and food, and is prepared by a tablet preparation method comprising the following steps:

(1) pulverizing Mentholum;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction, and filtering an extracting solution for later use:

(3) concentration: concentrating the extractive solution to obtain fluid extract; precipitating, filtering, collecting filtrate, recovering ethanol, and concentrating to obtain soft extract;

(4) and (3) drying: drying the thick paste obtained in the step (3) to obtain dry paste for later use;

(5) crushing: crushing the dry paste obtained in the step (4) to obtain dry paste powder for later use;

(6) and (3) granulating: taking the dry paste powder, conventionally granulating, drying and finishing;

(7) total mixing: adding menthol powder into the granules after finishing the granules and mixing;

(8) tabletting: tabletting by conventional method.

9. The medicinal and edible traditional Chinese medicine composition as claimed in claim 8, characterized in that the preparation method of the tablet is as follows:

(1) and (3) crushing menthol: weighing menthol, crushing, and sieving with a 100-mesh sieve for later use;

(2) extraction: taking honeysuckle, figwort, Chinese olive, platycodon root, emblic leafflower fruit and momordica grosvenori according to the proportion of the formula, adding water for extraction twice, 1 hour each time, adding 12 times of water for the first time, adding 10 times of water for the second time, and filtering the extract for later use:

(3) concentration: concentrating the extracting solution under reduced pressure at the temperature of 60-80 ℃ and the vacuum degree of 0.04-0.08 MPa to obtain clear paste with the relative density of 1.08-1.12; adding a proper amount of ethanol into the clear paste to ensure that the ethanol content is 70%, uniformly stirring, and standing for 48 hours at the temperature of 2-10 ℃; filtering, taking the filtrate, recovering ethanol under reduced pressure, and concentrating at 60-80 ℃ and 0.04-0.08 MPa to obtain thick paste with the relative density of 1.20-1.30;

(4) and (3) drying: drying by adopting a vacuum belt type, wherein the temperature of a heating plate is 110-120 ℃, the vacuum degree is 0.08-0.10 MPa, and collecting dry paste for later use;

(5) crushing: pulverizing the dry extract obtained by vacuum belt drying, and sieving with 100 mesh sieve;

(6) and (3) granulating: putting the dry paste powder into a mixer, adding lactose, dextrin and erythritol, uniformly mixing, adding 80-90% ethanol to prepare a soft material, granulating by using a 16-mesh sieve, and drying at the temperature of below 60 ℃ to obtain the dry paste;

(7) straightening: putting the dried granules into a crushing and granulating machine, and granulating by using a conical sieve with the diameter of 1.5 mm;

(8) total mixing: adding the menthol powder, the magnesium stearate and the sucralose into the granules after finishing the granules, uniformly mixing in a mixer for 8 r/min, and mixing for 20 minutes;

(9) tabletting: tabletting, and controlling the weight of each tablet to be 0.8 g.