A traditional Chinese medicine composition for treating allergic rhinitis, a traditional Chinese medicine preparation and a preparation method

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating allergic rhinitis and allergic dermatitis, a traditional Chinese medicine preparation and a preparation method. The traditional Chinese medicine composition is prepared from the following raw materials in parts by mass: Shouwuteng 1000-2000 parts, Digupi 1000-2000 parts, Baijianpi 800-1600 parts, Baizhi 600-1800 parts, Kuanfenghua 300-1100 parts, Jinyinhua 300-700 parts, Yekuhua 200-800 parts, Huaihua 400-600 parts and Gancao 400-1000 parts. The nine traditional Chinese medicine raw materials of the traditional Chinese medicine composition are used as monarch, minister, assistant and envoy, and the nine medicines are used together to achieve the effects of cooling blood and detoxifying, nourishing blood and dispelling evil, dispelling wind and relieving itching, and promoting lung and descending qi. Pharmacological experiments show that the formula can significantly reduce inflammatory factors in blood of allergic dermatitis mice, and the effect is good. In addition, the optimal extraction process of the nine medicines is selected, the preparation process is researched, the types and the optimal ratio of the excipients are investigated, and the experimental basis can be provided for hospital preparation registration, so that the traditional Chinese medicine composition can serve allergic disease patients such as AD and AR as early as possible.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating allergic rhinitis and atopic dermatitis, a traditional Chinese medicine preparation and a preparation method. BACKGROUND

[0002] Studies have shown that special environments (high temperature, high humidity, high cold, high heat, strong sunlight, etc.), seasonal changes, environmental pollution, including cigarette smoke, surface ozone, fine particulate matter in the air, and environmental pollutants such as occupational exposure to stimulant substances can increase the body's sensitivity to allergens, which can manifest as atopic dermatitis (AD) in the skin, such as eczema, dermatitis, and skin itching, and can also stimulate the nasal mucosa, induce local cytotoxicity, and thus induce the occurrence of allergic rhinitis (AR), which seriously affects the field combat capability of the point man, the health of outdoor workers, and the health of the general officers and soldiers. According to statistics, the prevalence rate of AD is increasing year by year worldwide, with a total prevalence rate of about 2.78% in China and up to 15% in developed countries in Europe and the United States. In the world, 10-40% of the population suffers from AR, and in the past six years, the number of AR patients in China has increased by nearly 100 million, with a total of more than 300 million patients, and the incidence rate is about 21.4%. A global disease burden study also shows that allergic diseases such as AD and AR have become a global burden.

[0003] The inventors use Fructus Kochiae and Cortex Dictamni as monarch drugs to clear heat, dry dampness, dispel wind, relieve itching, and detoxify; use Radix Polygoni Multiflori and Tribulus terrestris as minister drugs to nourish blood, dispel wind, and dredge collaterals to assist the monarch drugs in dispelling wind and relieving itching; use Honeysuckle, Chrysanthemum, and Sophora japonica as assistant drugs to clear heat, drain fire, cool blood, and detoxify; use Flower of Coltsfoot as a lung channel assistant drug, and Licorice to tonify the spleen and boost qi, clear heat and detoxify, and harmonize all drugs, both of which are servant drugs. The nine drugs are used together to achieve the effects of cooling blood, detoxifying, nourishing blood, dispelling evil, dispelling wind, relieving itching, and promoting lung qi. Pharmacological experiments show that the prescription can significantly reduce inflammatory factors in the blood of allergic dermatitis mice, with good results. In order to facilitate clinical deployment and use, the inventors optimize the best extraction process of the nine drugs, conduct preparation process research, investigate the types and best ratios of excipients, and provide experimental evidence for hospital preparation registration, so as to serve AD and AR patients as soon as possible.

[0004] The information disclosed in this Background section is only for the purpose of increasing the understanding of the background of the application and should not be taken as an acknowledgement or any form of suggestion that this information forms prior art that is already known in this field. SUMMARY

[0005] The application aims to provide a traditional Chinese medicine composition for treating allergic rhinitis and atopic dermatitis, a traditional Chinese medicine preparation, and a preparation method.

[0006] To achieve the above object, the present application provides the following technical solutions.

[0007] The first object of the present application is to provide a traditional Chinese medicine composition, which is prepared from the following raw materials in mass parts: Shouwuteng 1000-2000 parts, Digupi 1000-2000 parts, Baijianpi 800-1600 parts, Baizhi 600-1800 parts, Kuanfenghua 300-1100 parts, Jin yinghua 300-700 parts, Yekuhua 200-800 parts, Huaihua 400-600 parts, and Gancao 400-1000 parts.

[0008] Preferably, the traditional Chinese medicine composition is prepared from the following raw materials in mass parts: Shouwuteng 1300 parts, Digupi 1450 parts, Baijianpi 900 parts, Baizhi 700 parts, Kuanfenghua 400 parts, Jinyinghua 550 parts, Yekuhua 350 parts, Huaihua 450 parts, and Gancao 500 parts.

[0009] The second object of the present application is to provide a traditional Chinese medicine preparation, which comprises excipients, wetting agents, flavoring agents, and the traditional Chinese medicine composition.

[0010] The third object of the present application is to provide a preparation method of the traditional Chinese medicine preparation, which comprises the following steps:

[0011] S1. The raw materials for preparing the traditional Chinese medicine composition are weighed in mass parts, and then boiled in 10 times the mass of water for 3 times, with the first time of soaking for 15 min and each time of boiling for 1 h. The water decoctions are combined, concentrated, and spray-dried to obtain dry paste powder;

[0012] S2. The excipients and flavoring agents are added to the dry paste powder obtained in step S1, mixed uniformly, granulated with a wetting agent, and then the traditional Chinese medicine preparation is obtained.

[0013] Preferably, in step S2, the excipients are selected from one or more of lactose, maltodextrin, mannitol, erythritol, water-soluble starch, and maltitol; the flavoring agents are selected from one or more of acesulfame, aspartame, and stevia; and the wetting agent is ethanol.

[0014] Preferably, in step S2, the excipients are composed of maltodextrin and mannitol in a mass ratio of 1:1; the flavoring agent is stevia; and the wetting agent is

[0015] Preferably, in step S2, the mass ratio of the excipients to the dry paste powder is 1:1; the addition amount of the stevia is 3‰ of the dry paste powder; and the wetting agent is 750-950 mL / L of ethanol.

[0016] The fourth object of the present application is to provide the use of the traditional Chinese medicine composition or the traditional Chinese medicine preparation in the preparation of a drug for treating or preventing allergic rhinitis.

[0017] The fifth object of the present application is to provide the use of the traditional Chinese medicine composition or the traditional Chinese medicine preparation in the preparation of a medicament for treating or preventing allergic dermatitis.

[0018] Compared with the prior art, the present application has the following beneficial effects:

[0019] (1) The traditional Chinese medicine composition of the present application takes Fructus Kochiae and Cortex Dictamni as the monarch drug, which clears heat and dries dampness, dispels wind and relieves itching and detoxifies; takes Caulis Polygoni Multiflori and Tribulus terrestris as the minister drug, which nourishes blood, dispels wind, dredges collaterals, and assists the monarch drug in dispelling wind and relieving itching; takes Honeysuckle, Chrysanthemum and Sophora japonica as the assistant drug, which clears heat, drains fire, cools blood and detoxifies; takes Flower of Coltsfoot as the lung channel assistant drug, and Licorice Root supplements the spleen and tonifies qi, clears heat and detoxifies, and harmonizes various drugs, both of which are the minister drugs. The nine drugs are used together, which can cool blood and detoxify, nourish blood and dispel evil, dispel wind and relieve itching, and ventilate the lung and descend qi. Pharmacological experiments show that the prescription can significantly improve the symptoms of allergic rhinitis in guinea pigs and reduce the inflammatory factors in the blood of allergic dermatitis guinea pigs, with good effect.

[0020] (2) The present application optimizes the extraction process of the nine drugs, conducts formulation process research, investigates the types and optimal ratio of excipients, and provides experimental basis for hospital formulation registration, so as to make it serve allergic disease patients such as AD and AR as soon as possible. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 Specificity investigation chart for content determination of emodin;

[0022] Figure 2 Humidity rate of drug powder-excipient mixture at different times;

[0023] Figure 3 Nasal symptom score results of guinea pigs in each group;

[0024] Figure 4 Effect of Huamin Granules on the level of inflammatory cytokines in the serum of allergic rhinitis guinea pigs.

[0025] MAIN REFERENCE MARK EXPLANATION:

[0026] Figure 1 A: HPLC chromatogram of negative preparation without Caulis Polygoni Multiflori; B: HPLC chromatogram of emodin reference substance; C: HPLC chromatogram of Huamin Granule extract;

[0027] Figure 3 n=6, compared with the normal group, # P<0.5, ## P<0.05, ### P<0.01; compared with the model group, * P<0.5, ** P<0.05, *** P<0.01;

[0028] Figure 4 n=6, Note: compared with normal group, # P<0.5, ## P<0.05, ### P<0.01; compared with model group, * P<0.5, ** P<0.05, *** P<0.01. DETAILED DESCRIPTION

[0029] The following will be a clear and complete description of the technical solutions of the patent application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of the present application.

[0030] The instruments and materials used in the following examples are shown in Table 1 and Table 2.

[0031] Table 1 Instruments

[0032]

[0033]

[0034] Table 2 Materials

[0035]

[0036] Example 1 Chinese medicine composition

[0037] A Chinese medicine composition is prepared from the following raw materials: Shouwuteng 1300g, Digupi 1450g, Baijianpi 900g, Baizhi 700g, Kuandonghua 400g, Jin yinghua 550g, Yekuhua 350g, Huaihua 450g and Gancao 500g.

[0038] Example 2 Extraction process

[0039] 1. Test method

[0040] 1.1 Orthogonal test design and extraction method

[0041] Water is used as a solvent for decoction extraction, which conforms to the medication habits of traditional Chinese medicine and is the basic requirement for preparation records of medical institutions. Four factors [water addition (A), decoction time (B), decoction times (C), and soaking time (D)] that have greater impact on extraction effect are selected, and three levels of each factor are designed L9(34) 4Orthogonal test, the specific factor level arrangement see Table 3. According to the prescription amount of material, according to Table 4 experimental plan to decoct, respectively, combined with each water decoction, concentrated, dried, dry extract. With dry extract yield and polygonum multiflorum sylvestre content as index, the best extraction process is optimized.

[0042] Table 3 L9(3 4 Orthogonal test factor level arrangement table

[0043]

[0044] Note: Table 3 A: water; B: decoction time; C: decoction times; D: soaking time.

[0045] Table 4 orthogonal experiment plan arrangement table

[0046]

[0047] Note: Table 4 A: water; B: decoction time; C: decoction times; D: soaking time.

[0048] 1.2 Methodology investigation of polygonum multiflorum sylvestre content determination

[0049] 1.2.1 Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel as filler (5 μm, 4.6 mm x 25 cm); with acetonitrile-water (82:18) as mobile phase; detection wavelength is 320 nm; flow rate 0.8 mL / min; column temperature 30 DEG C. The theoretical plate number should not be less than 3 000 according to polygonum multiflorum sylvestre peak.

[0050] 1.2.2 Specificity investigation: take other eight kinds of medicinal materials except radix polygoni multiflori in the prescription, prepare into negative preparation without radix polygoni multiflori according to the above extraction process, and prepare into negative test solution according to the preparation method of test solution. According to the above chromatographic conditions, sample (20 μL of radix polygoni multiflori negative test solution, 20 μL of polygonum multiflorum sylvestre reference substance solution and 20 μL of test solution) is detected.

[0051] 1.2.3 Preparation of reference substance and linear series working solution: accurately weigh 12.7 mg of polygonum multiflorum sylvestre, place in a 25 mL volumetric flask, dissolve and dilute to the mark with methanol, shake well, get the concentration of 0.508 g / L of reference substance stock solution. Respectively take 0.05, 0.10, 0.25, 0.50, 1.00, 2.50 mL of reference substance stock solution in 5 mL volumetric flask, dilute to the mark with methanol, shake well, get the concentration of 5.08, 10.16, 25.40, 50.80, 101.60, 254.00 mg / L of series working solution, respectively, use 0.45 μm microporous filter membrane to filter, the filtrate is used as reference linear series working solution.

[0052] 1.2.4 Preparation of the test sample: 0.1 g of the test sample powder was accurately weighed into a 10 mL volumetric flask, dissolved with methanol and diluted to the mark, the mass was determined, ultrasonicated for 1 h, allowed to stand at room temperature, the mass was determined again, the loss was made up with methanol, shaken well, filtered, and the filtrate was collected.

[0053] 1.2.5 Preparation of the standard curve: 10 μL of the control substance of polygona tisflavone was injected into the liquid chromatograph according to the above chromatographic conditions, and the peak area was recorded. The concentration of polygontisflavone was used as the abscissa (X), and the peak area was used as the ordinate (Y).

[0054] 1.2.6 Precision test: the control substance solution of polygontisflavone was injected into the liquid chromatograph for 5 times, and the relative standard deviation (RSD) was calculated.

[0055] 1.2.7 Stability test: the control substance solution of polygontisflavone and the test sample solution were injected into the liquid chromatograph at 0, 2, 4, 8, 12, 24 and 36 h respectively, the peak area was determined, and the RSD value was calculated.

[0056] 1.2.8 Reproducibility test: 6 portions of the test sample, each 0.1 g, were prepared according to the above test sample preparation method, and the peak area of polygontisflavone was detected according to the above chromatographic conditions, the peak area was brought into the linear equation to calculate the content and the RSD value.

[0057] 1.2.9 Recovery test: 0.05 g of the fine powder of the extract of the Hua Min granules with a known content was taken, the control substance of polygontisflavone was added in a ratio of 1:0.8, 1:1 and 1:1.2 respectively, and the sample recovery experiment was carried out according to the above sample determination method. The average recovery rate and the RSD value were calculated according to the above chromatographic conditions.

[0058] 1.3 Determination of the content of polygontisflavone in the orthogonal test sample

[0059] 0.1 g of each of the orthogonal test samples was accurately weighed, prepared into a test sample solution according to the above test sample preparation method, 20 μL of the control substance and the sample solution was accurately taken respectively, injected into the liquid chromatograph, the peak area was determined, and the content of polygontisflavone in each sample was calculated.

[0060] 1.4 Verification of the water extraction process

[0061] The prescription amount of medicinal materials was weighed, decocted according to the above optimized extraction process, concentrated, spray dried to obtain the extract dry paste powder, the mass was determined, the dry extract yield was calculated. 0.1 g of the extract was weighed, prepared into a test sample solution according to the test sample solution preparation method, and the content of polygontisflavone was detected according to the chromatographic conditions.

[0062] 2. Results

[0063] The orthogonal experiment result analysis adopts the orthogonal experiment assistant II (professional edition) to carry out the direct analysis and variance analysis, and the linear regression equation and RSD are calculated by excel.

[0064] 2.1 Methodology results of content determination of polygonatum sibiricum in extract

[0065] 2.1.1 Specificity of content determination of polygonatum sibiricum

[0066] The results are shown in Figure 1 .

[0067] It can be seen from Figure 1 that the HPLC chromatographic results show that the solution of the negative preparation of radix polygonati multifidi has no obvious chromatographic peak at the corresponding retention time of the polygonatum sibiricum reference substance ( Figure 1 A), while the solution of the test sample has an obvious absorption peak at the corresponding retention time of the polygonatum sibiricum reference substance, and the peak shape is symmetrical and the separation degree is good ( Figure 1 B-C). It is shown that the chromatographic condition is strong in specificity, and can be used for the content determination of polygonatum sibiricum in the test sample.

[0068] 2.1.2 Standard curve and linear range

[0069] The peak area A of the linear series working solution of the reference substance is taken as the ordinate (Y), and the concentration C of polygonatum sibiricum is taken as the abscissa (X), and the regression equation is Y=46 296 065.52X-73237.27, R 2 =0.9997. It is shown that polygonatum sibiricum has a good linear relationship in the concentration range of 5.08 mg / L-0.254 g / L.

[0070] 2.1.3 Precision

[0071] The polygonatum sibiricum reference substance solution is repeatedly injected for 5 times, and the RSD is 0.73%. It is shown that the precision of the instrument is good.

[0072] 2.1.4 Stability

[0073] The sample is injected for 7 times within 36 h, the RSD of the polygonatum sibiricum reference substance is 1.15%, and the RSD of the test sample solution is 0.78%. It is shown that the polygonatum sibiricum reference substance and the test sample solution have good stability within 36 h.

[0074] 2.1.5 Repeatability

[0075] The peak area of the test sample is detected after repeated sampling, and the RSD is 0.18% (n=6). It is shown that the method has good repeatability.

[0076] 2.1.6 Recovery rate

[0077] The average recovery rate was 98.58% and RSD was 1.83% by measuring the sample prepared according to the above chromatographic conditions, which showed that the method had good recovery rate.

[0078] 2.2 Determination of the content of Polygonum multiflorum Thunb. glycosides in the extract and analysis of the results of orthogonal experiment

[0079] The results of determination of the content of the sample of orthogonal experiment are shown in Tables 5-6, and the results of variance analysis are shown in Table 7.

[0080] Table 5 Design of orthogonal experiment

[0081]

[0082] Note: In Table 5, A: amount of water; B: boiling time; C: boiling times; D: soaking time.

[0083] Table 6 Direct analysis of the results of orthogonal experiment

[0084]

[0085] Note: In Table 6, Ij, IIj and IIIj are the average values of the first, second and third levels of each factor, respectively; R represents the range of each level. A: amount of water; B: boiling time; C: boiling times; D: soaking time.

[0086] Table 7 Variance analysis of the results of orthogonal experiment

[0087]

[0088] Note: In Table 7, F0.05(2, 2) = 19.00 and F0.01(2, 2) = 99.00. A: amount of water; B: boiling time; C: boiling times; D: soaking time.

[0089] The results showed that the factors had effects on the yield of dry extract and the extraction amount of Polygonum multiflorum Thunb. glycosides. In terms of the yield of dry extract, the factors had effects in the order of C > A > B > D, and the third level was better for each factor, i.e. C3A3B3D3, and the factor C (boiling times) had significant effect on the yield of dry extract. In terms of the extraction amount of Polygonum multiflorum Thunb. glycosides, the factors had effects in the order of A > D > C > B, and the effect of A3D1C2B2 was the best, and the factor A (amount of water) had significant effect on the extraction amount of Polygonum multiflorum Thunb. glycosides. Since the factors B (boiling time) and D (soaking time) had no significant effect on the yield of dry extract and the extraction amount of Polygonum multiflorum Thunb. glycosides, A3C3B2D1 was determined as the preferred extraction process by considering the time and cost of energy consumption. That is, the prescribed amount of medicinal materials was weighed, 10 times the amount of water was added, and the mixture was boiled for 3 times, with 15 min of soaking for the first time and 1 h of boiling for each time.

[0090] 3. Verification of water extraction process

[0091] The extract of Huamin granules and the test sample were prepared according to the above-mentioned extraction process and test sample preparation method, and the dry powder yield and the content of homoisoflavonoid in the extract were calculated. The results of the determination of the content of homoisoflavonoid in each extract are shown in Table 8.

[0092] Table 8 Verification of water extraction process

[0093]

[0094] Compared with the results of each orthogonal experiment in Table 3, the dry powder yield and the content of homoisoflavonoid of the finally preferred process are both high. The RSDs of the three experiments are 2.58%, 2.63% and 1.79% respectively. Therefore, the final extraction process of Huamin granules is determined as follows: the prescription amount of medicinal materials is added with 10 times the amount of water for extraction for 3 times, the first soaking time is 15 min, and each decoction time is 1 h.

[0095] Example 3 Preparation process of the granules

[0096] According to the requirements of the medical institution preparation record system, and in combination with the taste, properties and treatment of the extract, the granules are preferred for the preparation of the granules. The dry paste powder has strong hygroscopicity, and the type and ratio of different excipients and the amount of wetting agent will affect the granulation. Therefore, in the optimization of the preparation process, the hygroscopicity and the angle of repose of the mixture of the drug powder and the excipients are used as the indicators to select the type and ratio of the excipients, and the properties of the soft material, the difficulty of granulation and the forming rate of the granules are used as the indicators to select the type and amount of the wetting agent, and the optimal preparation process of Huamin granules is comprehensively optimized.

[0097] 1. Test method

[0098] 1.1 Investigation of the type and ratio of excipients

[0099] The extract dry paste powder was weighed, and the corresponding excipients were added according to the ratio of drug powder-excipient 4:1, 3:1, 2:1 and 1:1, respectively. After being mixed uniformly, the mixture was laid flat on the bottom of a weighing bottle dried to constant weight, with a thickness of about 2 mm, and was accurately weighed. The dry paste powder was used as a control, and the weighing bottle was placed in a constant temperature and humidity box (25℃, saturated NaCl solution to maintain relative humidity of 75%), and was accurately weighed at 12, 18, 24 and 72 h, respectively. The hygroscopicity was calculated according to the following formula.

[0100] Hygroscopicity = (mass of the sample after hygroscopicity - mass of the sample before hygroscopicity) / mass of the sample before hygroscopicity x 100%.

[0101] 1.2 Investigation of wetting agents

[0102] According to Table 7, the drug powder-lactose (2:1, 1:1), the drug powder-mannitol (2:1, 1:1), the drug powder-maltodextrin (2:1, 1:1), the drug powder-maltodextrin-mannitol (2:0.5:0.5, 2:1:1) are weighed, different concentrations of ethanol are sprayed and stirred to mix evenly, and the soft material is prepared with "light hold into a ball, light pressure to scatter" as appropriate, extruded granulation with No. 1 sieve, dispersed in the air until no alcohol smell, dried at 65°C, and the whole granulation. The granules that pass through No. 1 sieve but not No. 5 sieve are taken to calculate the granulation rate.

[0103] 1.3 Selection of flavoring agents

[0104] Considering the drug needs of diabetic population, sucrose is avoided in the preparation, and three flavoring agents, such as sweetener, aspartame and stevia, and different proportions are selected for trial flavoring. 10 g of sample is dissolved in 50 mL of water, and 10 healthy subjects are evaluated for taste scoring, with a maximum score of 5 and a minimum score of 0.

[0105] 1.4 Preparation process verification

[0106] Three batches of samples verified by orthogonal experiment are taken, each 50 g, and 25 g of maltodextrin and 25 g of mannitol and 3‰ of stevia are added and mixed evenly, and granulation is performed with 900 mL / L of ethanol, and the properties, granulation rate, solubility and taste are evaluated.

[0107] 2. Results

[0108] 2.1 Type and ratio of excipients

[0109] The results are shown in Figure 2 and Table 9.

[0110] From Figure 2 it can be seen that, compared with the dry paste powder without excipients, the hygroscopicity of the samples with excipients is reduced. With mannitol, maltodextrin and lactose as excipients, the hygroscopicity is lower, and the effect is better with 1:1 or 1:2.

[0111] The dry paste powder and excipients are mixed in different proportions for granulation, and the ease of sieving, granulation rate, angle of repose and solubility are used as indicators to optimize the most suitable excipient and drug-excipient ratio, and the results are shown in Table 9.

[0112] Table 9 Investigation of types and ratios of excipients

[0113]

[0114] From Table 9, it can be seen that the drug powder-maltodextrin-mannitol (2:1:1) has the best granulation effect.

[0115] 2.2 Investigation of wetting agents

[0116] Respectively try different concentrations of ethanol spray stirring mixed evenly, "light hold together, light pressure is scattered" for the preparation of soft material, with No. 1 sieve extrusion granulation, air to no alcohol flavor after 65 ℃ drying, whole particle. Take over No. 1 sieve but not 5 sieve particles, calculate the particle forming rate.

[0117] The results are shown in Table 10.

[0118] Table 10 Investigation of wetting agent for granulation (n = 3)

[0119]

[0120] As can be seen from Table 10, when 900 mL / L of ethanol is used as a wetting agent, the soft material has a suitable property, is easy to granulate, and has a high particle forming rate.

[0121] 2.3 Selection of flavoring agent

[0122] Considering the medication needs of diabetic population, sucrose is avoided in the preparation, and three flavoring agents, i.e. acesulfame, aspartame and stevioside, and different proportions are selected for trial preparation. 10 g of sample is dissolved in 50 mL of water, and 10 healthy subjects are asked to evaluate the taste and score, with the highest score being 5 and the lowest score being 0. The results are shown in Table 11.

[0123] Table 11 Taste score of different flavoring agents (n = 10)

[0124]

[0125] As can be seen from Table 11, on the basis of the above determined excipients, the solution obtained by adding 3 ‰ stevioside has a slightly sweet taste and a slightly bitter aftertaste, and has the highest score, so 3 ‰ stevioside is selected as the flavoring agent.

[0126] 2.4 Preparation process verification

[0127] Three batches of samples verified by orthogonal experiment are taken, each 50 g, and 25 g of malt dextrin and 25 g of mannitol and 3 ‰ stevioside are added and mixed evenly, and granulation is performed with 900 mL / L of ethanol, and the properties, particle forming rate, solubility and taste are evaluated. The results are shown in Table 12.

[0128] Table 12 Preparation process verification results

[0129]

[0130]

[0131] As can be seen from Table 12, the preparation process of the present application is stable, and has a high particle forming rate.

[0132] Example 4 Pharmacological experiment

[0133] 1. Test method

[0134] 1.1 Model establishment, grouping and administration

[0135] After 3 days of adaptive feeding, guinea pigs were randomly divided into normal control group and model group. The allergic rhinitis model was induced according to the method of Yang Chao et al. and HIGGINST S et al. The modeling was divided into sensitization period, challenge period and maintenance period (administration period).

[0136] Sensitization: On the 1st and 8th day of the experiment, animals in each group were intraperitoneally injected with 1 mL of OVA containing 1 mg and 100 mg of Al(OH )3 The blank group was also given the same amount of normal saline by the same method.

[0137] Challenge period: On the 15th day of the experiment, all animals except the normal control group were placed in a prepared aerosol box and treated with 1% OVA for 10 minutes. The guinea pigs showed symptoms of rhinitis. The blank group was treated with normal saline for 10 minutes. This was done once every two days for 14 days. After the 14th day of aerosolization, the model group was randomly divided into model control group, dexamethasone group, and high, medium and low dose groups of Huamin.

[0138] Maintenance period: On the 29th day of the experiment, the maintenance period began, with 2% OVA normal saline solution being administered intranasally, 0.1 mL per animal per day. Different drugs were also administered at the same time. The model control group was given the same volume of normal saline by gavage, once a day for 14 days.

[0139] The administration dose was: dexamethasone 0.12 mg / kg, high dose of Huamin 3.52 g / kg, medium dose 1.76 g / kg, and low dose 0.88 g / kg.

[0140] 1.2 Collection of specimens

[0141] Serum specimens: 24 hours after the last administration, guinea pigs were anesthetized with intraperitoneal injection of 10% chloral hydrate at a dose of 3 mL / kg, then blood was collected from the abdominal aorta, centrifuged at 2000 rpm for 5 minutes, and serum was collected and stored at -20°C. ELISA was used to detect inflammatory factors such as IL-27, IL-4, IL-5, IL-13, OVA-sIgE and IFN-γ.

[0142] Tissue sample: After blood sampling and guinea pig death, open the chest cavity and remove the right lung, and place it in a -80℃ environment for preservation. Fix the left upper lung or left lower lung (right lung for alveolar lavage) with neutral formaldehyde and store at 4℃ for lung tissue HE staining sections. Nasal mucosa pathological specimen: The nasal mucosa tissue of guinea pigs is peeled off from the oral cavity and fixed with formaldehyde solution and placed in a 4℃ environment for later use in nasal tissue HE staining section experiments.

[0143] 1.3 Index detection

[0144] 1.3.1 Symptom observation

[0145] On the 7th and 14th day of the experiment, the symptoms of nasal discharge, sneezing and nasal itching of the mice in each group were recorded, and the cumulative score was calculated according to the method of Li Li et al. Nasal discharge to nostril counts 1 point, through the anterior naris counts 2 points, full-face discharge counts 3 points; 1-3 internal sneezing counts 1 point, 4-10 counts 2 points, 11 and above counts 3 points; mild nasal itching, scratching nose a few times counts 1 point, scratching nose more than counts 2 points, total score counts 8 points.

[0146] 1.3.2 ELISA method for detecting inflammatory cytokines such as IL-27, IL-4, IL-5, IL-13, OVA-sIgE and IFN-γ in blood

[0147] In this experiment, the ELISA kit of Quanzhou Ruixin Biological Technology Co., Ltd. was used for detection, and the specific operation was carried out according to the instruction manual.

[0148] 2. Results

[0149] Data statistical analysis was performed using Graphpad 5.0 software. Data were expressed as mean ± standard deviation, and differences between groups were analyzed by t test. P<0.5 was considered statistically significant.

[0150] 2.1 Comparison of nasal inflammation symptom scores of guinea pigs in each group

[0151] The results are shown in Table 13 and Figure 3 .

[0152] Before modeling, the guinea pigs in each group were active and the nasal symptom scores were not statistically significant.

[0153] Table 13 Comparison of nasal symptom scores of guinea pigs in each group

[0154]

[0155]

[0156] Note: Compared with the normal group, ###P<0.01; compared with the model group, *P<0.5, **P<0.05, ***P<0.01.

[0157] From Table 13 and Figure 3 It can be seen that the food intake of the model group guinea pigs was slightly reduced on the 14th day of intervention (14th day after sensitization), the 28th day (14th day of the challenge period) and the 43rd day (14th day of administration), but they were obviously irritable and the nasal symptom scores were significantly higher than those of the blank group. The scores of the dexamethasone group and the Hua Sensitive Granules of each dose group were significantly lower than those of the model group. It should be noted that the Hua Sensitive Granules here were prepared according to the extraction optimal process of Example 2 and the preparation optimal process of Example 3 from the traditional Chinese medicine composition of Example 1.

[0158] 2.2 Effect of Hua Sensitive Granules on the levels of inflammatory cytokines in the serum of guinea pigs with allergic rhinitis

[0159] The results are shown in Figure 4 .

[0160] From Figure 4 It can be seen that compared with the normal control group, the levels of IL-4, IL-5, IL-13, IL-27 and OVA-sIgE in the serum of the model group guinea pigs were significantly increased, and the level of IFN-γ was significantly decreased. After treatment with dexamethasone and different doses of Hua Sensitive Granules, the levels of inflammatory factors such as IL-4, IL-5, IL-13, IL-27 and OVA-sIgE were significantly reduced, and the level of IFN-γ was significantly increased.

[0161] Discussion

[0162] 1. Selection of extraction process

[0163] According to the "Implementation Details of Shaanxi Province Medical Institutions for the Record Management of Traditional Process Prepared Chinese Medicine Preparations (Trial)" issued by the Shaanxi Provincial Drug Administration and the Shaanxi Provincial Administration of Traditional Chinese Medicine in 2019, the preparations for record preparation in medical institutions in Shaanxi Province can only be traditional dosage forms prepared by traditional process

[10] . Therefore, water was selected as the solvent for decoction extraction in this study. Four factors that have a greater impact on extraction efficiency were selected, and three levels of each factor were investigated. In the selection of indicators, the dry extract yield directly affects the prescription amount and the amount of taking the preparation, and the content of functional ingredients determines the efficacy of the preparation. However, the specific functional ingredients of traditional Chinese medicine prescriptions are not completely clear, so the content of functional ingredients in the extract was detected according to the "Chinese Pharmacopoeia" 2020 edition

[11] The content of each prescription medicine was measured, and the total content and dry extract yield were given a weight score of 5:5 and 8:2, respectively, for orthogonal analysis. The results showed that each factor level had no significant effect on the score. Then, each component content and dry extract yield were given different weights for scoring analysis, and it was found that the content of atractyloside was significantly related to different extraction processes. Therefore, the dry extract yield and atractyloside content were used as indicators for process evaluation. Although the atractyloside content in the extraction process verification sample was high, it did not reach the highest content in the orthogonal experiment. This may be due to the small amount of extraction in the orthogonal extraction, the use of vacuum drying, and the large amount of extraction in the later orthogonal process verification, followed by spray drying. However, the efficacy components of the preparation have not been fully elucidated, so the dry extract yield and atractyloside content are used as indicators to optimize the final extraction process.

[0164] 2. Selection of content determination indicators

[0165] In this study, the content of the extract was determined by selecting the content determination method of each prescription medicine in the 2020 edition of Chinese Pharmacopoeia.

[11] Among them, the jian medicine white peels jujube ketone and amur cork tree ketone belong to terpenoids, which can be dissolved in organic solvents such as chloroform, dichloromethane, ethyl acetate, and acetone, and are difficult to dissolve in water, so it is difficult to detect in the extract of this preparation; the content of glycyrrhizin and ammonium glycyrrhizinate is relatively high, which can reach 1.6% and 4.2%, but considering that licorice is widely used in traditional Chinese medicine prescriptions for its role in harmonizing various drugs, it is not representative; the content of rutin in sophora flower and syringa in honeysuckle flower and chlorogenic acid is also a component in most traditional Chinese medicines, which is not specific; the content of trichosanthin in trichosanthes kirilowii is determined by ultraviolet spectrophotometry, which has low precision and interference in the determination of compound extract; the evaporation light scattering detection of gynostemma pentaphyllum saponin has special requirements for equipment. Therefore, the atractyloside in the gynostemma pentaphyllum in the prescription is finally selected as the content determination index. Moreover, different extraction processes have a significant effect on the content of atractyloside, so the content of atractyloside in the extract can reflect the extraction efficiency and process stability.

[0166] 3. Selection of dosage form and excipient

[0167] Traditional Chinese medicine granules are a new dosage form developed on the basis of traditional Chinese medicine decoction and syrup, etc. It not only maintains the characteristics of fast absorption and rapid action of decoction, but also overcomes the disadvantages of decoction such as inconvenience in decoction, large dosage, easy moldy and deterioration, etc. Therefore, the prescription for treating surface syndrome is often prepared into granules. The preparation process of granules is relatively simple, which can be applied to industrial production, and the dosage is small, which is convenient for taking, storing and transporting.

[0168] The common excipients of traditional Chinese medicine granules include dextrin, soluble starch, lactose, sucrose, etc. Lactose is slightly expensive, and some patients are intolerant to lactose, which can cause adverse reactions such as diarrhea, abdominal distension, vomiting, etc. Sucrose and starch can be metabolized to glucose in vivo. In view of the increasing incidence of diabetes in China, the selection of excipients in this study is preferably erythritol, mannitol, maltitol and other sugar substitutes, which can serve as excipients for granules and also have the function of flavoring, and can minimize the amount of excipients. It is found through comparison that the granules prepared by using 900 mL / L ethanol have the lowest moisture absorption rate and the best granulation effect.

[0169] In summary, the extraction process and preparation process of Huamin granules are preliminarily determined, which lays a foundation for subsequent research and development.

[0170] The foregoing description of specific exemplary embodiments of the application is intended to be illustrative only and is not intended to limit the application to the precise forms described. Many modifications and variations are possible in light of the above teachings without departing from the spirit or essential characteristics of the application. The exemplary embodiments are chosen and described in order to explain the principles of the application and its practical application to thereby enable others skilled in the art to best utilize the application and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the scope of the application be defined by the claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for treating allergic rhinitis, characterized in that, It is prepared from the following raw materials by weight: 1000-2000 parts of Polygonum multiflorum vine, 1000-2000 parts of Kochia scoparia fruit, 800-1600 parts of Dictamnus dasycarpus root bark, 600-1800 parts of Tribulus terrestris fruit, 300-1100 parts of Tussilago farfara flower, 300-700 parts of Lonicera japonica flower, 200-800 parts of Chrysanthemum indicum flower, 400-600 parts of Sophora japonica flower, and 400-1000 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition for treating allergic rhinitis according to claim 1, characterized in that, It is prepared from the following raw materials by weight: 1300 parts of Polygonum multiflorum vine, 1450 parts of Kochia scoparia fruit, 900 parts of Dictamnus dasycarpus root bark, 700 parts of Tribulus terrestris fruit, 400 parts of Tussilago farfara flower, 550 parts of Lonicera japonica flower, 350 parts of Chrysanthemum indicum flower, 450 parts of Sophora japonica flower, and 500 parts of Glycyrrhiza uralensis.

3. A traditional Chinese medicine preparation for treating allergic rhinitis, characterized in that, The traditional Chinese medicine preparation for treating allergic rhinitis includes excipients, humectants, flavoring agents, and the traditional Chinese medicine composition for treating allergic rhinitis as described in claim 2.

4. A method for preparing a traditional Chinese medicine preparation for treating allergic rhinitis as described in claim 3, characterized in that, Includes the following steps: S1. Weigh the raw materials for the preparation of the traditional Chinese medicine composition according to the mass ratio, add 10 times the mass of water and decoct 3 times. Soak for 15 minutes the first time and decoct for 1 hour each time. Combine the decoctions, concentrate and spray dry to obtain dry extract powder. S2. Add the excipients and flavoring agents to the dry powder obtained in step S1, mix evenly, and granulate with a wetting agent to obtain the traditional Chinese medicine preparation.

5. The method for preparing the traditional Chinese medicine preparation for treating allergic rhinitis according to claim 4, characterized in that, In step S2, the excipient is selected from one or more of lactose, mannitol, maltodextrin, mannitol, erythritol, water-soluble starch, and maltitol; the flavoring agent is selected from one or more of cyclamate, aspartame, and stevia; and the humectant is ethanol.

6. The method for preparing the traditional Chinese medicine preparation for treating allergic rhinitis according to claim 5, characterized in that, In step S2, the excipient is composed of maltodextrin and mannitol in a 1:1 mass ratio; the flavoring agent is stevia.

7. The method for preparing the traditional Chinese medicine preparation for treating allergic rhinitis according to claim 6, characterized in that, In step S2, the mass ratio of the excipient to the dry powder is 1:1; the amount of stevia added is 3‰ of the dry powder; and the wetting agent is 750-950 mL / L ethanol.

8. The use of the traditional Chinese medicine composition for treating allergic rhinitis according to claim 1 or the traditional Chinese medicine preparation for treating allergic rhinitis according to claim 3 in the preparation of a drug for treating allergic rhinitis.

Images