CN100362983C - A traditional Chinese medicine preparation for reducing fever in children and its preparation method - Google Patents

Abstract

The present invention relates to a Chinese medical preparation for infantile defervescence and a preparation method thereof, particularly to oral medicinal liquor for infantile defervescence and a preparation method thereof, and the present invention belongs to the technical field of medicine. The preparation technology of the present invention uses water distillation extraction to determin parameters; the present invention has the advantages of little loss of paeonol, good mouth feel, high biologic utilization, feasible operation, easy control and convenient mass production. Compared with western medicine for defervescence, the oral administration liquor for infantile defervescence has the advantages of smaller side effect, moderate defervescence, endurance and stability, and performs the functions of expelling wind, relieving exterior syndromes, eliminating toxicity and relieving sore-throat; the oral medicinal liquor for infantile defervescence not only takes temporary solution, but also effects a permanent cure, and temperature rapidly drops without relapse; thus, the oral medicinal liquor for infantile defervescence is a preferred medicinal preparation for doctors, patriarches and sick infants.

Description

A traditional Chinese medicine preparation for reducing fever in children and its preparation method

Technical field:

The invention relates to a traditional Chinese medicine preparation for reducing fever in children and a preparation method thereof, in particular to Xiaoer Tui oral liquid and a preparation method thereof. Belongs to the field of pharmaceutical technology.

Technical background: In children, the viscera are delicate, the skin is sparse and thin, and the external defenses are not solid. They may feel the evil of wind-heat again, or the cold turns from heat, so they have fever and aversion to wind; Accumulation of pyretic toxins has symptoms such as mumps swelling and high fever. Therefore, once a child with a cold develops a high fever, it is urgent to reduce the fever, and at the same time it needs to be ventilated to let the evil have a way out. Pediatric antipyretic preparations are developed based on the above-mentioned pathology.

Pediatric antipyretic preparations such as Xiaoer antipyretic oral liquid and Xiaoer antipyretic granules are included in the sixth volume of "Drug Standards of the Ministry of Health Traditional Chinese Medicine Prescriptions". Forsythia is distilled with water steam, the distillate is collected, and the dregs and other medicinal materials are decocted twice. It is the key medicine for clearing away heat and expelling pathogenic factors. Scutellaria baicalensis, Folium Isatidis, Radix Isatidis clears heat and detoxifies, reduces swelling and sore throat; Gardenia clears and relieves internal heat of the triple energizer, Baiwei, Moutan cortex and Gardenia clears heat and cools blood, clears heat in the blood, clears internal heat, and matches with the prodrug. Li Shuangqing; Zhonglou and Dilong clear away heat and calm convulsions, which can prevent febrile convulsions in children. When used together, these medicines can clear away heat and penetrate the surface, detoxify and relieve sore throat.

At present, both traditional Chinese medicine and Western medicine antipyretic drugs are mainly based on sweating. However, due to the side effects of Western medicine, it is particularly prominent for children. For example, ibuprofen can stimulate and damage the gastric mucosa. Aspirin can also induce asthma and may cause Rainey's syndrome when it is used in children with acute febrile illness, especially influenza and chickenpox. Therefore, the World Health Organization advocates not using this drug for children with fever caused by acute respiratory infection. Even acetaminophen, which has less side effects recommended by the World Health Organization, can not be underestimated the impact on children's blood cells, while traditional Chinese medicine has certain advantages in this regard. Compared with the antipyretic western medicine, Xiaoer Antipyretic Oral Liquid has less side effects, and the antipyretic is milder, lasting and stable. Children's Antipyretic Oral Liquid can relieve wind, relieve exterior, detoxify and sore throat. It can treat both the symptoms and the root cause. The body temperature drops quickly and rarely rebounds. It is an acceptable treatment method for doctors, parents and children. Therefore, it is of great practical significance to carry out in-depth research on the mechanism of antipyretic in children, prevent adverse reactions of western medicines, develop new Chinese patent medicine preparations of antipyretic drugs for children, and give full play to the advantages of traditional Chinese medicine in treating fever in children.

In the existing antipyretic preparations for children, such as oral liquid and granules, the distillation process parameters in the preparation process are not strictly formulated, resulting in a large loss of paeonol. This is because paeonol, the active ingredient in Moutan cortex, has a low melting point of 49.5-50, poor water solubility, and is extremely volatile. Therefore, paeonol cannot be detected in the finished product cooked with group medicines. And this technology is difficult to control again in the production process, is unfavorable for large-scale production, unstable in storage period, easily produces settlement. At the same time, children in the febrile period are quite sensitive to the sense of taste, especially they tend to refuse to take bitter medicinal liquids. Even if they are fed, they sometimes spit them out. These are the difficulties that have not been overcome in the prior art. Therefore, it is necessary to improve the process and improve the quality of the preparation.

Invention content:

The invention provides a traditional Chinese medicine preparation for reducing fever in children.

The antipyretic traditional Chinese medicine preparation for children of the present invention is made of the following traditional Chinese medicine raw materials in weight ratio: 50-450 parts of Folium Isatidis, 30-270 parts of Radix Radix, 30-270 parts of Honeysuckle, 30-270 parts of Forsythia, 30 parts of Gardenia ～270 parts, 30～270 parts of Moutan bark, 30～270 parts of Scutellaria baicalensis, 20～180 parts of light bamboo leaves, 20～180 parts of Dilong, 15～135 parts of Chonglou, 30～270 parts of Bupleurum, 20～180 parts of Baiwei share.

In the present invention, the above-mentioned traditional Chinese medicine raw materials are extracted and processed to obtain pharmaceutical active substances, and then prepared into any pharmaceutically acceptable preparation form by mixing the pharmaceutical active substances with an appropriate amount of pharmaceutically acceptable adjuvants through the conventional technology of pharmacy.

For example, the preferred Chinese medicine formula is: Daqingye 150g, Banlangen 90g, honeysuckle 90g, forsythia 90g, gardenia 90g, Moutan bark 90g, scutellaria baicalensis 90g, light bamboo leaves 60g, earthworm 60g, Chonglou 45g, Bupleurum 90g, white Wei 60g.

In the above composition, the weight of the traditional Chinese medicine is calculated based on the crude drug, and this formula can be made into 1000 doses of pharmaceutical preparations. The 1000 doses refer to the finished pharmaceutical preparations, such as 1000 capsules, 1000 tablets, 1000 grams of granules, 1000 ml of oral liquid, etc., as granules can also be made into large packages, such as 100-500 Bags, specifically 100 bags, 125 bags, 200 bags, 250 bags, 500 bags, etc., each bag can be used as 1-2 doses.

The above composition can be made into a preparation of 50-1000 doses. If it is used as a patch, it can be made into 1000 tablets, and it can be made into 1000 capsules. When using it, the usage and dosage can be determined according to the condition of the child. It can be taken 1-3 times a day. Time, each 1-20 doses, can take 50-1000 times altogether. As granules, make 125 bags, take 1-2 bags each time, and take 62.5-125 times in total.

The above components are proportioned by weight, and can be increased or decreased according to the corresponding proportion during production. For example, the unit of kilogram or ton can be used for large-scale production, and the unit of milligram can also be used for small-scale production. Increase or decrease, but the ratio of the raw medicinal material weight ratio among the components remains unchanged.

The proportion of the above weight ratio is obtained through scientific screening. For special patients, such as severe or mild, obese or thin patients, the proportion of the composition can be adjusted accordingly, and the increase or decrease does not exceed 100%. Change.

The traditional Chinese medicine raw materials in the above composition, especially the ministerial medicine and the adjuvant medicine, can also be replaced by appropriate Chinese medicines with the same medicinal properties, and the medicine effect of the replaced Chinese medicine preparation remains unchanged.

The pharmaceutically active substance of the present invention can be prepared by the following method: This preparation method constitutes the key of the present invention.

For the above twelve flavors, crush Moutan Cortex, Bupleurum, and Forsythia medicinal materials until they all pass 45 mesh, but not 30 mesh, add water according to the ratio of medicine powder to water 1/10, distill with water for 2 hours, and collect the distillate; Add 4-20 times the amount of water to decoct the remaining green leaves and other nine flavors for 2-5 times, each time for 0.5-2 hours, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content more than 70%, and let it stand. place. Take the supernatant to recover ethanol, concentrate to more than 200ml, add water and stir evenly, let stand, take the supernatant, filter, the filtrate is concentrated to an appropriate amount, and the concentrated solution and the distillate are combined to form the pharmaceutical active substance of the present invention.

Taking the pharmaceutical active substance as a raw material and adding pharmaceutically acceptable auxiliary materials, it can be prepared into any pharmaceutical preparation form according to the conventional technology of pharmacy.

The Chinese medicine preparation of the present invention can be any pharmaceutically acceptable dosage form, and these dosage forms include: oral liquid, film, enema, patch, syrup, granule, tablet, capsule, pill, powder, ointment, pill , injections, suppositories, creams, sprays, dropping pills, sustained-release preparations, controlled-release preparations, preferably oral liquids.

The pharmaceutical preparation of the present invention, its preparation for oral administration may contain common excipients, such as sweeteners, binders, fillers, diluents, tableting agents, lubricants, disintegrants, coloring agents, corrective agents, etc. Flavoring and wetting agents, and tablets may be coated if necessary.

Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as flavoring agents such as fruit pulp, sucrose, aspartame, grape syrup, fructose, maltitol, stabilizers such as sodium carboxymethylcellulose, sorbitol, syrup, Methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, or hydrogenated edible fats, emulsifiers such as lecithin, sorbitan monooleate, or acacia; nonaqueous Carriers (which may include edible oils) such as almond oil, fractionated coconut oil, oily esters such as glycerol, propylene glycol or ethanol; preservatives such as sodium benzoate or propylene glycol or paraben or propylparaben or sorbic acid and, if desired, conventional flavoring or coloring agents.

Suitable fillers include cellulose, mannitol, lactose and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycolate. Suitable lubricants, such as magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.

Solid oral compositions can be prepared by common methods such as mixing, filling, and tabletting. Repeated mixing is performed to distribute the active material throughout those compositions where large amounts of fillers are used.

For injections, liquid unit dosage forms are prepared containing the active material of the invention in association with a sterile carrier. Depending on the carrier and concentration, the compound can be suspended or dissolved. Solutions are usually prepared by dissolving the active substance in a carrier and filter sterilizing before filling into a suitable vial or ampoule, which is then sealed. Adjuvants such as a local anesthetic, preservatives and buffering agents can also be dissolved in the vehicle. To increase its stability, the composition can be frozen after filling vials and the water removed under vacuum.

The pharmaceutical preparation of the present invention can optionally add a suitable pharmaceutically acceptable carrier when it is prepared into a medicament, and the pharmaceutically acceptable carrier is preferably selected from: mannitol, sorbitol, sodium metabisulfite, sodium bisulfite, Sodium thiosulfate, cysteine hydrochloride, thioglycolic acid, methionine, vitamin C, disodium EDTA, calcium sodium EDTA, monovalent alkali metal carbonates, acetates, phosphates or their aqueous solutions, hydrochloric acid, acetic acid, Sulfuric acid, phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and its Derivatives, alginate, gelatin, polyvinylpyrrolidone, glycerin, Twain 80, agar, calcium carbonate, calcium bicarbonate, surfactant, polyethylene glycol, cyclodextrin, β-cyclodextrin, phospholipid materials , kaolin, talc, micropowder silica gel, magnesium carbonate, calcium stearate, magnesium stearate, etc.

According to the present invention, the most preferred preparation form is an oral liquid, and its basic preparation method includes mixing the above-mentioned pharmaceutical active substance with a flavoring agent, a stabilizer, and a preservative, such as: the above-mentioned pharmaceutical active substance is mixed with more than 400 g of sucrose. Mix the syrup, then add stabilizer and appropriate amount of preservatives, adjust the total amount with water to the specified amount, stir well, filter, fill, and sterilize to get ready.

Specifically, for the above twelve flavors, crush the cortex moutan, bupleurum, and forsythia medicinal materials until they all pass 45 mesh, but not 30 mesh, add water at a ratio of 1/10 of the powder to water, distill with water for 2 hours, and collect the distillate; Add 10 times the amount of water to decoct the dregs and the rest of the green leaves and other nine flavors for two times, 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to about 200ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another 400g of sucrose to make a syrup, combine with the above liquid medicine and distillate, then add appropriate amount of stabilizer and preservative, adjust the total amount to 1000ml, stir well, filter, fill and sterilize to get ready.

The best preparation method of the oral liquid of the present invention is: 150g of Daqingye, 90g of Radix Isatidis, 90g of Honeysuckle, 90g of Forsythia, 90g of Gardenia, 90g of Moutan Cortex, 90g of Scutellaria, 60g of Bamboo Leaf, 60g of Dilong, 45g of Chonglou, Bupleurum 90g, Baiwei 60g, the above twelve flavors, crush the medicinal materials of Moutan Cortex, Bupleurum, and Forsythia until they all pass 45 mesh, but not 30 mesh, add water according to the ratio of medicine powder to water 1/10, that is, 2700ml, and steam distill 2h, collect the distillate; decoct the dregs and the rest of the green leaves and other nine flavors with 7350ml of water twice, 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, stand still. Take the supernatant to recover ethanol, concentrate to 200ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another 400g of sucrose to make syrup, combine with the above liquid medicine and distillate, then add 8g of sodium carboxymethylcellulose and 0.1% of sodium benzoate, adjust the total amount to 1000ml, stir well, filter, fill, and sterilize, namely have to.

Said water distillation process is characterized in that cortex Moutan, Radix Bupleurum and Forsythia medicinal materials are pulverized until they all pass through 45 meshes, but cannot pass through 30 meshes, add water according to the ratio of medicine powder to water at 1/10, and steam distill for 2 hours; said water The decoction process is characterized in that the final alcohol content is 70%, the ratio of sucrose, sodium carboxymethyl cellulose and the concentration of the medicinal solution is 50:25:1, the best is the final alcohol content of 70%, sucrose 400g, carboxymethyl fiber Sodium 8g, liquid concentration 200ml.

The preparation of the preferred oral liquid of the present invention, its preferred formula is composed as follows:

Pharmaceutical active substance of the present invention: Folium Isatidis 150g, Radix Radix 90g, Honeysuckle 90g, Forsythia 90g, Gardenia 90g, Cortex Moutan 90g, Scutellaria baicalensis 90g, Bamboo leaves 60g, Earthworm 60g, Chonglou 45g, Bupleurum 90g, Wei 60g.

Flavorings: Sucrose, Aspartame, Grape Syrup, Fructose and Maltitol.

Stabilizer: sodium carboxymethylcellulose.

Preservatives: Ethylparaben, Methylparaben, Sodium Benzoate, Benzoic Acid, and Sorbic Acid.

The most preferred formula consists of the following:

Pharmaceutical active substance of the present invention: Folium Isatidis 150g, Radix Radix 90g, Honeysuckle 90g, Forsythia 90g, Gardenia 90g, Cortex Moutan 90g, Scutellaria baicalensis 90g, Bamboo leaves 60g, Earthworm 60g, Chonglou 45g, Bupleurum 90g, Wei 60g.

Flavoring agent: Aspartame

Stabilizer: sodium carboxymethylcellulose

Preservative: Sodium Benzoate

The above most preferred formula composition is obtained through screening, so that the mouthfeel is greatly improved.

Compared with the prior art contained in traditional Chinese medicine preparations, the children's antipyretic oral liquid of the present invention has definite parameters of the water distillation process, which ensures the extraction of the active ingredient of paeonol, avoids a large loss of paeonol caused by the original process, and is easy to detect Paeonol has improved drug efficacy, stabilized quality, good taste, and high bioavailability; at the same time, it is feasible to operate, easy to control, and convenient for mass production.

The above advantages are further confirmed by the following process experiments:

1 The best process experiment of the present invention extracting volatile oil (comprising paeonol):

1.1 The present invention adopts co-water distillation method to extract, take 30g of pulverized samples of Cortex Moutan, Bupleurum and Forsythia, set 3 distillation parameters: A distillation time; B the ratio of pulverized samples to the amount of water added during distillation; C medicinal material pulverization degree , as the three factors investigated.

1.1.1 Choose 3 sets of values for each parameter, which are: A ₁ Distillation time 2h; A ₂ Distillation time less than 2h; A ₃ Distillation time greater than 2h; B ₁ The ratio of powder to water is 1/20, that is, add water 900ml; B ₂ The ratio of medicine powder to water is 1/15, that is, add 675ml of water; the ratio of _B3 medicine powder to water is 1/10, that is _, add 450ml of water _; Mesh; C ₃ medicinal materials are crushed until they all pass 60 mesh, but not 45 mesh. All parameters were combined into 9 treatments, and the combinations conformed to the Latin square design, see Table 1 for details.

1.2 Analysis of the components contained in the volatile oil:

1.2.1 GC conditions: the chromatographic column is a DB5 quartz capillary column, 30m×0.25mm×0.25μm; the carrier gas is high-purity helium (99.999%); the column flow rate is 1ml Pmin, splitless; the front pressure of the column: 100kPa; the injection port Temperature 220°C; injection volume 1μl. Temperature program: column temperature 40°C for 1min, 10°C Pmin to 200°C for 3min. DSQ conditions: ionization mode EI, electron energy 70eV; interface temperature 210°C, ion source temperature 200℃; flow scanning range 50~350; solvent delay 4.0min; emission current 100μA.

Table 1 Variation matrix of distillation parameters for distillation of essential oils (Latin square design)

serial number combination serial number combination serial number combination 123 A₁B₁C₃A₁B₂C₁A₁B₃C₂ 456 A₂B₁C₃A₂B₂C₃A₂B₃C₁ 789 A₃B₁C₁A₃B₂C₂A₃B₃C₃

2 Results and Analysis

2.1 The influence of different distillation parameters on the yield of volatile oil (see Table 2)

Table 2 The yield of volatile oil after different distillation parameter combinations

parameter combination Volatile oil yield % Parameter combination Volatile oil yield% parameter combination Volatile oil yield% A₁B₁C₃A₁B₂C₁A₁B₃C₂ 1.7671.6332.417 A₂B₁C₃A₂B₂C₃A₂B₃C₁ 1.2500.7171.108 A₃B₁C₁A₃B₂C₂A₃B₃C₃ 0.3670.4830.417

It can be seen from Table 2 that the distillation conditions of 9 different parameter combinations significantly affect the yield of volatile oil, and the combination with the highest yield is the combination A ₂ B ₂ C ₃ , with an oil yield as high as 3.54%; The combination with the lowest yield is A ₁ B ₃ C ₂ , with an oil yield of 0.367%, a difference of 6.6 times.

In order to compare the size of the influence of 3 distillation conditions on the yield of volatile oil, this experiment has carried out analysis of variance (table 3), as can be seen from table 3: in this experiment, the factor that has the greatest impact on the yield of volatile oil is distillation time, followed by The ratio of pulverized medicinal powder to added water has the least influence on the pulverization degree of medicinal materials.

Table 3 Analysis of variance of volatile oil production

source of variation sum of square degrees of freedom Variance F value F0.05 F0.01 A factor B factor 0.2053.499 twenty two 0.1031.750 34.1675833.167

C Factor Total Error 0.2990.0064.009 228 0.1500.003 49.833

2.2 The influence of different distillation parameters on paeonol contained in the volatile oil is shown in Table 4

Table 4 Changes in the percentage of main components of volatile oil obtained by water distillation with different parameter combinations

Element 1 2 3 4 5 6 7 8 9 Myrcene phenol Forsythia volatile oil Forsythia glycosides Bupleurum long-chain aldehyde paeonol 0.050.161.000.491.1662.68 0.070.140.890.391.0269.64 0.050.130.720.391.1193.11 0.040.181.040.461.0065.43 0.050.170.760.440.9660.09 0.070.211.200.511.0767.51 0.120.251.520.611.5155.59 0.140.271.630.661.5058.47 0.170.311.970.701.6357.52

Through the GC-DSQ analysis of the volatile oil distilled by different distillation parameters, the relative percentages of the six main components were obtained (Table 4). From the experimental results, it can be seen that the relative content of paeonol in the combination with a distillation time of 2 hours is relatively high, and the content of paeonol in combination 3 (A ₁ B ₃ C ₂ ) reaches 93.11%, indicating that the distillation time is directly Affect the distillation rate of paeonol. Except for paeonol, the relative percentages of other components appear in other distillation time combinations.

3 Conclusion

In the prior art, although there are many methods for extracting volatile oil, distillation is the most commonly used method. This requires us to carefully select distillation parameter values and determine the best combination of parameters to improve distillation yield and oil quality. From this From the experimental results of the invention, it can be seen that the distillation parameters have a greater impact on the yield and composition of the volatile oil, and the distillation time has a significant impact on the yield of the volatile oil. The higher the yield of the oil is, the more the distillation time is 2 hours. Furthermore, in the case of paeonol, the relative content of paeonol was highest in the combination with a distillation time of 2 hours. Therefore in the present invention, the optimum distillation condition of setting is distillation time 2h, adds water 450ml, and medical material is pulverized to all through 45 orders, but can not pass 30 orders.

In order to stabilize the quality and make the taste good, we have conducted a series of screening experiments on the excipients we added:

Experiment 1: Select the optimal ratio of drug solution volume and excipients through orthogonal experiments, and investigate the stability of the preparation:

1 Experimental materials

1.1 According to the method of the present invention, the decoction concentrated solution obtained by mixing the medicinal dregs after steam distillation and distillation of Cortex Moutan, Bupleurum, and Forsythia with the other nine flavors such as green leaves, alcohol precipitation, distillate, and sucrose, carboxymethyl Fiber sodium mixed, that is.

1.2 Both sucrose and sodium carboxymethylcellulose are used for medicine.

2 Experimental methods and results

Choose L ₉ (3 ⁴ ) orthogonal design table to arrange experiments.

Table 1 Factor levels

level A alcohol precipitation % B sucrose g C sodium carboxymethylcellulose g D Concentrated liquid volume ml 123 506070 400600800 678 400300200

Table 2 Orthogonal experiment results of L ₉ (3 ⁴ )

Test No. A B C D   Clarity observation during storage period 123456789 111222333 123123123 123231312 123312231 After 5 minutes, half of the amount settled after 25 minutes, after 25 minutes, there was almost no settlement, after 30 minutes, there was a slight amount of sedimentation, after 25 minutes, after a slight amount of sedimentation, after 5 minutes, after a slight amount of sedimentation, after 20 minutes, after 4 minutes, after 3 minutes, the half amount of sedimentation

Conclusion: From the data in the table, it can be seen that the stability of the process A ₁ B ₃ C ₂ D ₂ and A ₁ B ₃ C ₂ D ₂ is good, and the quasi-storage period is evenly mixed, but A ₁ B ₃ C ₂ D ₂ The amount of sucrose used in the process is large, and the dosage is large, so choose A ₁ B ₃ C ₂ D ₂ . That is, the alcohol precipitation is 70%, the ratio of sucrose, sodium carboxymethyl cellulose and the concentration of the medicinal solution is 50:25:1; the best is the alcohol precipitation of 70%, 400g of sucrose, 8g of sodium carboxymethylcellulose, and concentrated medicinal solution Volume 200ml. Precipitate with 70% ethanol, prepare each batch of oral liquid according to the process ratio, observe at room temperature for 1 year, and the stability is good; sodium carboxymethylcellulose is used as a stabilizer, after 30 minutes, there is almost no sedimentation, the liquid is uniform, and the appearance is good.

Experiment 2: The choice of flavoring agent to examine the mouthfeel of the preparation.

The experiment is as follows: according to the amount of sucrose in Experiment 1 of the present invention, we replaced sucrose with aspartame, fruit grape pulp, fructose, and maltitol respectively, divided into 5 groups, prepared oral liquid according to the technology of the present invention, and compared its mouthfeel in turn. as follows:

The impact of table 1 flavoring agent on the present invention is investigated

group Acceptance of children (taking compliance) Taste score 1 aspartame group   Very easy for children to take Fresh and sweet 98

2 grape pulp group 3 fructose group 4 maltitol group 5 sucrose group Children are willing to take. Children are willing to take. Children are not willing to take more. They are easy to vomit. Children are not willing to take more, and feeding is difficult. Fragrance, good and fresh taste, good and fresh taste, good and slightly bitter taste 95939190

The above investigations showed that the addition of flavoring agents can enhance children's medication compliance, and the order of effect is aspartame > fruit grape pulp > fructose > maltitol > sucrose.

Experiment 3: Choice of preservatives:

Because the ointment of the present invention contains a large amount of sugar, it is easy to breed microorganisms and mildew during storage, thereby affecting the quality of the medicine. Therefore, an appropriate amount of preservative can be added to the ointment of the present invention, but if the preservative is used improperly, it will also affect the quality of the medicament. The following are the experimental results for the selection of preservatives:

project Appearance changes Taste 30 days 60 days 90 days 120 days 180 days 0.1% Sodium Benzoate - - - - - no change 0.2% sodium benzoate - - - - - no change 0.1% Benzoic Acid - - - - - Slight tongue numbness 0.2% Benzoic Acid - - - - - Slight tongue numbness 0.03% Ethylparaben - + ++ ++ ++ There is a peculiar smell 0.05% Methylparaben - - - - - There is a peculiar smell 0.05% potassium sorbate - - 0 0 0 Rancid 0.2% potassium sorbate - - - 0 0 Rancid

Note: - indicates no change; + indicates a small amount of mold; ++ indicates mold; 0 indicates fermentation rancidity.

According to the comparison of experimental results in the table, we choose sodium benzoate as preservative.

Because when sodium benzoate is used as a preservative, the amount is bigger, there is no obvious change to the quality of medicines, but it will cause damage to the human body. In this preparation, the amount of sodium benzoate is preferably no more than 0.2%. for:

project Appearance changes Taste 30 days 60 days 90 days 120 days 180 days

0.05% sodium benzoate - - + ++ +++ There is a peculiar smell 0.10% Sodium Benzoate - - - + + There is a peculiar smell 0.15% Sodium Benzoate - - - - - no change 0.20% sodium benzoate - - - - - no change 0.25% sodium benzoate - - - - - no change 0.3% sodium benzoate - - - - - Slight tongue numbness

According to experimental result in the table, the effective usage amount of sodium benzoate is 0.10%-0.20% in this preparation.

Beneficial effects: the main pharmacodynamic test results show that the children's antipyretic oral liquid of the present invention has obvious antipyretic and anti-inflammatory effects, and these pharmacological effects are confirmed by the following test examples, and the test results provide a basis for clinical application . The following test examples are used to further illustrate the present invention.

Test Example 1 The antipyretic effect of Xiaoer antipyretic oral liquid of the present invention on infectious fever in rabbits.

1 Materials and methods

1.1 Animals: 56 New Zealand big-eared white rabbits (provided by the Animal Laboratory of Guiyang Medical College), weighing 2.0±0.2kg, half male and half male.

1.2 Drugs:

Xiaoer Tuire Granules prepared in accordance with the process contained in the sixth volume of "Drug Standards of the Ministry of Health Chinese Medicine Prescriptions", hereinafter referred to as drug A;

The antipyretic oral liquid for children made by the process of the present invention is hereinafter referred to as medicine B.

1.3 Method: Take 56 New Zealand big-eared white rabbits, both male and female, and divide them into 7 groups randomly, 8 rabbits in each group. Fasting without water for 12h. The rabbits were fixed at a room temperature of 20±1°C, and after being quiet, the rectal temperature was measured twice consecutively with a PD-U digital thermometer (made in Germany), which was calibrated by a standard thermometer (made in Chongqing Medical Instrument Factory) before the experiment. Every 30 minutes, the average value was taken as the normal body temperature. After the normal body temperature was determined, the animals in each group were intravenously injected with typhoid and paratyphoid triple A and B bacteria liquid at 1.0mlPkg. At 60 minutes, the temperature change after heating was measured according to the above method. Then, one group was fed with normal water as a negative control group, three groups were fed with different doses of Xiaoer Tuire Granules, and the remaining three groups were fed with different doses of Xiaoer Tuire Oral Liquid. Measure the body temperature at 30, 60, 120, 180, 240, and 300 minutes after the administration, and carry out paired t-test between the normal body temperature of each group of animals and the body temperature before the administration after the animals in this group were given heat. Statistical significance of post-pyrogenic body temperature. At the same time, the body temperature of the treated animal group and the control group were subjected to inter-group t-test, and the body temperature changes after heating were calculated and compared respectively. The test results are as follows:

Attached Table: Effect of Xiaoer Tuire Oral Liquid on Febrile Rabbits

Group Dose (g/kg) Normal body temperature (°C) Body temperature 1h after heating (℃)   Body temperature after administration (°C) 0.5h 1h 2h 3h 4h 5h Control group drug A drug B -0.20.40.80.20.40.8 38.3±0.738.3±0.238.3±0.638.3±0.638.2±0.438.33±0.138.1±0.4 40.4±0.5^#40.3±0.3^#40.5±0.6^#40.5±0.6^#40.3±0.3^#40.5±0.2^#40.4±0.4^# 40.6±0.640.2±0.340.6±0.540.6±0.540.5±0.440.2±0.240.6±0.5 40.8±0.740.4±0.640.4±0.539.6±0.2^△*40.1±0.6^△39.6±0.2^△*39.5±0.3 ^△* 40.6±0.440.3±0.140.2±0.139.8±0.339.4±0.539.5±0.639.4±0.5 40.5±0.340.2±0.140.2±0.139.5±0.239.6±0.439.5±0.339.3±0.5 40.3±0.539.7±0.439.5±0.439.3±0.539.8±0.539.2±0.639.4±0.3 39.8±0.239.6±0.339±0.439±0.439.6±0.539±0.439.1±0.3

#P<0.01Compared with normal body temperature 1h after heating before administration.

*P<0.01Compared with body temperature after heating 1h after administration and before administration.

△P<0.01Compared with the body temperature of the control group at 1h after administration in each administration group.

2 results

One hour after the rabbit was intravenously injected with the triple bacteria solution, a pyrogenic effect was produced, and the body temperature increased significantly. Compared with before heating, the difference was significant (P<0.01). After the fever-induced rabbits were fed with Xiaoer Tuire Granules (Drug A) and Xiaoer Tuire Oral Liquid (Drug B), the body temperature of the Drug B group decreased significantly. Significant (P<0.01); while drug A did not lower body temperature significantly. Comparing the body temperature of each administration group 1h after administration with the body temperature of the control group at the corresponding time, the difference in the drug group B is very significant (P<0.01), and the difference in the drug group A is not significant, see the attached table.

The results show that the Xiao'er antipyretic oral liquid of the present invention can reduce infectious fever in rabbits.

Test example 2 Anti-inflammatory effect of children's antipyretic oral liquid of the present invention

1 Materials and methods

1.1 Animals: 40 Kunming male mice (provided by the Animal Laboratory of Guiyang Medical College), weighing 27±0.5g.

1.2 Drugs:

Drug A: Aspirin (commercially available)

Medicine B: the antipyretic oral liquid for children made by the process of the present invention;

Blank control group.

1.3 Method: 40 male mice were randomly divided into Xiaoer Tuire Oral Liquid high-dose group 40ml·kg ^-1 , Xiaoer Tuire Oral Liquid small-dose group 10ml·kg ^-1 , Xiaoer Tuire Oral Liquid low-dose group 30ml ·kg ^-1 and the blank control group, 10 rats in each group, were administered intragastrically (40ml·kg ^-1 ) once, and the control group was given the same amount of distilled water. After 1.5 hours of administration, the left ear of each mouse was smeared with 30ul of xylene to cause inflammation, and the right ear was used as a control. After 30 minutes of inflammation, the mice were killed, and ear pieces were respectively punched at the same position with a 9mm diameter puncher, weighed, and the left ear was used as a control. The ear weight minus the right ear weight was used as the degree of swelling. The administration group was compared with the control group, and the swelling rate was calculated. See Table 1.

The impact of table 1 oral liquid of the present invention on the swelling of the small auricle due to xylene

The results show that the oral liquid of the present invention has obvious inhibitory effect on the swelling of the small auricle caused by xylene.

Detailed ways

The present invention will be further described below in conjunction with the examples, and the following examples are only used to illustrate the present invention, and the present invention is not limited.

Example 1

Daqingye 150g, Banlangen 90g, Honeysuckle 90g, Gardenia 90g, Moutan bark 90g, Bupleurum 90g, Forsythia 90g, Scutellaria baicalensis 90g, Bamboo leaf 60g, Dilong 60g, Chonglou 45g, Baiwei 60g, sucrose 400g, carboxylate Sodium methylcellulose 8g and sodium benzoate 1g

For the above twelve flavors, crush Moutan Cortex, Bupleurum and Forsythia medicinal materials until they all pass 45 mesh, but not 30 mesh, add water according to the ratio of medicine powder to water 1/10, that is, add 2700ml of water, steam distill for 2 hours, and collect the distillate Add 7350ml of water to decoct the dregs of the medicinal herbs and other nine flavors such as green leaves for two times, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 200ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another 400g of sucrose to make syrup, combine with the above liquid medicine and distillate, then add sodium carboxymethylcellulose and sodium benzoate, adjust the total amount to 1000ml, stir well, filter, fill, and sterilize to get ready.

Example 2

Daqingye 150g, Banlangen 90g, Honeysuckle 90g, Gardenia 90g, Moutan bark 90g, Bupleurum 90g, Forsythia 90g, Scutellaria baicalensis 90g, Bamboo leaf 60g, Dilong 60g, Chonglou 45g, Baiwei 60g, Aspartame 400g, sodium carboxymethylcellulose 8g and sodium benzoate 1g

For the above twelve flavors, crush Moutan Cortex, Bupleurum, and Forsythia until all of them pass through 45 meshes, but not 30 meshes. Add water according to the ratio of powder to water 1/10, that is, add 2700ml of water, steam distill for 2 hours, and collect the distillate Add 7350ml of water to decoct the dregs of the medicinal herbs and other nine flavors such as green leaves for two times, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 200ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another aspartame to make syrup, combine with the above liquid medicine and distillate, then add sodium carboxymethylcellulose and sodium benzoate, adjust the total amount to 1000ml, stir well, filter, fill, and sterilize to obtain .

Example 3 Folium Folium 50g, Radix Isatidis 30g, Honeysuckle 30g, Forsythia 30g, Gardenia 30g, Moutan bark 30g, Scutellaria baicalensis 30g, Bamboo leaves 20g, Dilong 20g, Chonglou 15g, Bupleurum 30g, Baiwei 20g, fruit Grape pulp 400g, sodium carboxymethylcellulose 8g and sodium benzoate 0.34g

For the above twelve flavors, crush Moutan Cortex, Bupleurum, and Forsythia until they pass through 45 meshes, but not 30 meshes, add water according to the ratio of powder to water 1/10, that is, add 900ml of water, steam distill for 2 hours, and collect the distillate Add 2450ml of water to decoct the dregs of the medicine and the rest of the leaves and other nine flavors for two times, 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 200ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another grape pulp to make a syrup, combine it with the above-mentioned medicinal liquid and distillate, add sodium carboxymethylcellulose and sodium benzoate, adjust the total amount to 1000ml, stir well, filter, fill, and sterilize.

Example 4

Daqingye 450g, Banlangen 270g, Honeysuckle 270g, Forsythia 270g, Gardenia 270g, Moutan bark 270g, Scutellaria baicalensis 270g, Bamboo leaves 180g, Dilong 180g, Chonglou 135g, Bupleurum 270g, Baiwei 180g, sucrose 800g, carboxylate Sodium methylcellulose 8g and sodium benzoate 3g

For the above twelve flavors, crush Moutan Cortex, Bupleurum and Forsythia medicinal materials until they all pass 45 mesh, but not 30 mesh, add water according to the ratio of medicine powder to water 1/10, that is, add 8100ml of water, steam distill for 2 hours, and collect the distillate Add 22050ml of water to decoct medicinal residues and other nine flavors such as green leaves twice, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 600ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another 800g of sucrose to make syrup, combine with the above liquid medicine and distillate, add sodium carboxymethyl cellulose and sodium benzoate, adjust the total amount to 1000 doses, stir well, filter, fill, and sterilize to get ready.

Example 5

Daqingye 50g, Banlangen 270g, Honeysuckle 30g, Moutan bark 270g, Forsythia 270g, Bupleurum 30g, Gardenia 30g, Scutellaria baicalensis 30g, Bamboo leaf 180g, Dilong 20g, Chonglou 135g, Baiwei 180g, sucrose 600g, carboxylate Sodium methylcellulose 8g and sodium benzoate 1.5g

For the above twelve flavors, crush Moutan Cortex, Bupleurum and Forsythia medicinal materials until they all pass 45 mesh, but not 30 mesh, add water according to the ratio of powder to water 1/10, that is, add 5700ml of water, steam distill for 2 hours, and collect the distillate add water 9250ml and decoct twice for 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 298ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another 600g of sucrose to make a syrup, combine with the above liquid medicine and distillate, add sodium carboxymethylcellulose and sodium benzoate, adjust the total amount to 1000ml, stir well, filter, fill, and sterilize to get ready.

Example 6 Folium Folium 450g, Radix Isatidis 30g, Honeysuckle 270g, Cortex Moutan 30g, Forsythia 30g, Bupleurum 270g, Gardenia 270g, Scutellaria baicalensis 270g, Danzhuye 20g, Dilong 180g, Chonglou 15g, Baiwei 20g, A Spartame 400g, sodium carboxymethylcellulose 8g and sodium benzoate 1.86g

For the above twelve flavors, crush Moutan Cortex, Bupleurum, and Forsythia until all of them pass through 45 meshes, but not 30 meshes. Add water according to the ratio of medicine powder to water 1/10, that is, add 3300ml of water, steam distill for 2 hours, and collect the distillate Add 15250ml of water to decoct medicinal residues and other nine flavors such as green leaves twice, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 369ml, add water, stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount. Take another 600g of sucrose to make syrup, combine with the above liquid medicine and distillate, then add sodium carboxymethylcellulose and sodium benzoate, adjust the total amount to 1000 doses, stir well, filter, fill, and sterilize to get ready.

Embodiment 7 film dosage

Daqingye 150g, Banlangen 90g, Honeysuckle 90g, Gardenia 90g, Moutan bark 90g, Bupleurum 90g, Forsythia 90g, Scutellaria baicalensis 90g, Bamboo leaf 60g, Dilong 60g, Chonglou 45g, Baiwei 60g, film-forming material carboxylate Sodium methylcellulose solution (1:10) 800g and propylene glycol 30g

For the above twelve flavors, crush Moutan Cortex, Bupleurum and Forsythia medicinal materials until they all pass 45 mesh, but not 30 mesh, add water according to the ratio of medicine powder to water 1/10, that is, add 2700ml of water, steam distill for 2 hours, and collect the distillate Add 7350ml of water to decoct the dregs of the medicinal herbs and other nine flavors such as green leaves for two times, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content 70%, and let it stand. Take the supernatant to recover ethanol, concentrate to 200ml, add water, stir well, let stand, take the supernatant, concentrate to an appropriate amount. Separately take sodium carboxymethyl cellulose solution, combine it with the above liquid medicine and distillate, add propylene glycol to grind it evenly, place it to remove air bubbles, apply it on flat glass to form a film, dry it, remove the film and cut it into an appropriate size, and pack it in the packaging material , to obtain the film agent.

Example 8 Granules

Daqingye 150g, Banlangen 90g, Honeysuckle 90g, Gardenia 90g, Moutan bark 90g, Bupleurum 90g, Forsythia 90g, Scutellaria baicalensis 90g, Bamboo leaf 60g, Dilong 60g, Chonglou 45g, Baiwei 60g, sucrose 1000g

According to Example 1, the obtained medicinal material concentrate and distillate are combined, sucrose is added, and granules can be prepared according to the granule preparation method.

Example 9 tablet

Daqingye 150g, Banlangen 90g, Honeysuckle 90g, Gardenia 90g, Moutan bark 90g, Bupleurum 90g, Forsythia 90g, Scutellaria baicalensis 90g, Bamboo leaves 60g, Dilong 60g, Chonglou 45g, Baiwei 60g, carboxymethyl starch Sodium 30g, dextrin 30g, magnesium stearate 10g

According to Example 1, the obtained medicinal material concentrate and distillate were combined, spray-dried, pulverized, added with auxiliary materials, and compressed into tablets to obtain tablets.

Embodiment 10 capsules

Daqingye 150g, Banlangen 90g, Honeysuckle 90g, Gardenia 90g, Moutan bark 90g, Bupleurum 90g, Forsythia 90g, Scutellaria baicalensis 90g, Bamboo leaves 60g, Dilong 60g, Chonglou 45g, Baiwei 60g, Starch 30g, Talc 10g

According to Example 1, the obtained medicinal material concentrate and distillate were combined, spray-dried, pulverized, added with auxiliary materials, and packed into capsules to obtain capsules.

Claims (6)

1. A traditional Chinese medicine preparation for reducing fever in children, characterized in that it consists of 50 to 450 parts of Folium Folium, 30 to 270 parts of Radix Radix, 30 to 270 parts of Honeysuckle, 30 to 270 parts of Forsythia, 30 to 270 parts of Gardenia, Moutan cortex 30-270 parts, Scutellaria baicalensis 30-270 parts, Bamboo leaves 20-180 parts, Dilong 20-180 parts, Chonglou 15-135 parts, Bupleurum 30-270 parts, Baiwei 20-180 parts and medicinal Prepared from auxiliary materials, the preparation is to extract and process the proportioned traditional Chinese medicine to obtain pharmaceutical active substances, and use the pharmaceutical active substances as raw materials to mix with pharmaceutical auxiliary materials, characterized in that the pharmaceutical active substances are prepared by the following method , crush the medicinal materials of Moutan Cortex, Bupleurum, and Forsythia until they all pass through 45 meshes, add water according to the ratio of medicinal powder to water 1/10, distill with water for 2 hours, and collect the distillate; add 4- Decoct with 20 times of water for 2-5 times, 0.5-2 hours each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, add ethanol to make the alcohol content more than 70%, let it stand; take the supernatant to recover ethanol, Concentrate to more than 200ml, add water, stir evenly, let stand, take the supernatant, filter, the filtrate is concentrated to an appropriate amount, and the concentrated solution and the distillate are combined to form the pharmaceutical active substance of the present invention. 2. The Chinese medicine preparation according to claim 1, characterized in that it is oral liquid, film, enema, patch, granule, tablet, capsule, pill, powder, ointment, elixir, injection, suppository, cream , spray, drop pill, sustained-release preparation or controlled-release preparation. 3. The Chinese medicine preparation according to claim 2, which is an oral liquid. 4. the Chinese medicine preparation of claim 3 is characterized in that, its prescription is composed as follows: Pharmaceutical active substance of the present invention: Folium Isatidis 150g, Radix Radix 90g, Honeysuckle 90g, Forsythia 90g, Gardenia 90g, Cortex Moutan 90g, Scutellaria baicalensis 90g, Bamboo leaves 60g, Earthworm 60g, Chonglou 45g, Bupleurum 90g, Wei 60g Flavorings: Sucrose, Aspartame, Grape Syrup, Fructose, Maltitol Stabilizer: sodium carboxymethylcellulose Preservatives: Ethylparaben, Methylparaben, Sodium Benzoate, Benzoic Acid, Sorbic Acid. 5. the Chinese medicine preparation of claim 4 is characterized in that, its prescription is composed as follows: Pharmaceutical active substance of the present invention: Folium Isatidis 150g, Radix Radix 90g, Honeysuckle 90g, Forsythia 90g, Gardenia 90g, Cortex Moutan 90g, Scutellaria baicalensis 90g, Bamboo leaves 60g, Earthworm 60g, Chonglou 45g, Bupleurum 90g, Wei 60g Flavoring agent: Aspartame Stabilizer: sodium carboxymethylcellulose Preservative: Sodium Benzoate. 6. The preparation method of the Chinese medicine preparation according to claim 1, characterized in that, through the following steps, 150g of Folium Folium, 90g of Radix Radix, 90g of Flos Lonicerae, 90g of Forsythia, 90g of Gardenia, 90g of Cortex Moutan, 90g of Scutellaria, 60g of Bamboo Leaf, Dilong 60g, Chonglou 45g, Bupleurum 90g, Baiwei 60g, and the above twelve flavors, grind the medicinal materials of peony bark, Bupleurum and forsythia until they all pass 45 meshes, but not 30 meshes, according to the ratio of powder to water 1 Add water to /10, that is, 2700ml, steam distill for 2h, collect the distillate; add 7350ml of water to decoct the dregs and other green leaves and other nine flavors for two times, each time for 1 hour, combine the decoction, filter, and concentrate the filtrate to an appropriate amount. Add ethanol to make the alcohol content 70%, let it stand still; take the supernatant to recover ethanol, concentrate to 200ml, add water and stir well, let stand, take the supernatant, filter, and concentrate the filtrate to an appropriate amount; take another 400g of sucrose to make Combine the syrup with the above liquid medicine and distillate, add 8 g of sodium carboxymethylcellulose and 0.1% of sodium benzoate, adjust the total amount to 1000 ml, stir well, filter, fill, and sterilize to obtain final product.