CN114470060B - A traditional Chinese medicine composition for treating allergic rhinitis and preparation method thereof - Google Patents

Abstract

The invention provides a traditional Chinese medicine composition for treating allergic rhinitis and a preparation method thereof, wherein the traditional Chinese medicine composition comprises honeysuckle, isatis root, houttuynia cordata, borneol and pharmaceutic adjuvant, and the pharmaceutic adjuvant is selected from butyrolactone modified sulfobutyl-beta-cyclodextrin sodium, water and a penetrating agent laurocapram. The butyrolactone modified sulfobutyl-beta-cyclodextrin is adopted to include the insoluble honeysuckle extract, the isatis root extract and the houttuynia cordata extract, so that the solubility of the extracts is greatly increased, the extracts are easy to release and absorb, the absorption of the medicine is promoted, and the bioavailability is improved; the borneol in the formula can promote the absorption of the three extracts, can increase the comfort of the nasal spray preparation and effectively treat allergic rhinitis. The Chinese medicinal composition has stable quality.

Description

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

technical field

The present invention relates to the field of pharmaceutical preparations, relates to a traditional Chinese medicine composition for allergic rhinitis and a preparation method thereof, and more particularly relates to a traditional Chinese medicine composition for treating allergic rhinitis composed of honeysuckle, Radix isatidis, Houttuynia cordata, and borneol and its preparation method.

Background technique

Allergic rhinitis is allergic rhinitis, which refers to the release of mediators (mainly histamine) mediated by IgE after atopic individuals are exposed to allergens, and a variety of immune active cells and cytokines are involved. Noninfectious inflammatory disease of the mucosa. There are three necessary conditions for its occurrence: the specific antigen is the substance that causes the body's immune response; the atopic individual is the so-called individual difference and allergic constitution; the specific antigen and the atopic individual meet. Allergic rhinitis is a global health problem that causes many diseases and lost labor.

As the problem of air pollution becomes more and more prominent, the threat to human health, especially the respiratory system, becomes more and more obvious. Relevant data show that major pollutants in the air such as PM2.5, ozone, nitrogen dioxide, sulfur dioxide and automobile exhaust may induce the occurrence and aggravation of symptoms of allergic rhinitis, asthma and upper respiratory diseases.

Allergic rhinitis is a chronic inflammatory response disease of the nasal mucosa that is mediated by IgE after atopic individuals are exposed to allergens. Sneezing, hypersecretion of the nose, and swelling of the nasal mucosa are the main features. Although allergic rhinitis is not a serious disease, 70% of severe allergic rhinitis will affect sleep, 94% will affect life and work, and its impact on quality of life even exceeds that of major diseases such as hypertension and diabetes. And allergic rhinitis may be combined with various diseases such as otitis media, sinusitis, nasal polyps, asthma, etc., which is more harmful to health.

At present, the treatment of allergic rhinitis is mainly carried out by desensitization, hormone and immunization methods. Usually, the short-term curative effect is significant, but the effect is difficult to maintain after stopping the drug, and the above-mentioned desensitization drugs and hormone drugs cannot be used for a long time, and the effect cannot be maintained. Side effects such as mucous membrane dryness, epistaxis, taste, and headache appear.

At present, there is no ideal medicine and method for treating allergic rhinitis clinically. During the absorption and distribution of systemic drugs such as oral or injection, some drugs are destroyed by the gastrointestinal tract and liver or shunted by blood circulation, and the effective concentration that actually reaches the lesion is very low, which makes it difficult to achieve therapeutic effects, and can induce drug resistance of bacteria and cause death. The disease becomes chronic, so the curative effect is poor and the cure rate is low; commonly used topical medications, such as Dibijing, only have the ability to constrict blood vessels and improve the nasal congestion symptoms caused by rhinitis. Drug-induced rhinitis. Laser therapy uses the high temperature generated by the laser beam to burn the lesion to eliminate inflammatory tissues and pathogenic bacteria. Although it has curative effect, laser therapy is invasive, cumbersome and expensive. Therefore, the medicines and methods currently used for the treatment of allergic rhinitis have defects such as slow effect, poor curative effect, long course of treatment, low cure rate, large toxic and side effects, and high cost to patients.

Chinese medicine has been used for thousands of years to treat allergic rhinitis. In the Tang Dynasty, Sun Simiao treated the disease from the perspective of syndrome differentiation of lung and kidney deficiency. Modern Chinese medicine also proposes various plans for the treatment of allergic rhinitis from various angles, some of which are additions and subtractions of ancient prescriptions, and some of which are new formulations. Feng Rongchang used Yupingfeng powder to treat allergic rhinitis very well; there is Xanthia powder, which is recorded in Volume 5 of "Jisheng Fang" and mainly treats nasal sinusitis and turbid nasal discharge. , Peppermint, Fritillaria, Tempeh, Chrysanthemum, and Licorice. It is also used to treat allergic rhinitis with good results. Li Ming proposed a decoction made of raw materials such as Rubia, Comfrey, Fangfeng, Chanyi, Dilong, Xu Changqing, Wumei and other raw materials to treat allergic rhinitis by means of randomized controlled research.

The inventors of the present application have proposed a traditional Chinese medicine composition for effectively treating allergic rhinitis in long-term practice. The composition has a simple formula, a simple manufacturing process, convenient administration, and less toxic and side effects, and can well improve the rhinitis symptoms of patients. , and not easy to relapse.

Contents of the invention

The object of the present invention is to provide a traditional Chinese medicine composition for treating allergic rhinitis comprising honeysuckle, Radix isatidis, Houttuynia cordata and Borneol and a preparation method thereof. The traditional Chinese medicine composition has stable quality and can effectively treat allergic rhinitis.

For realizing the object of the present invention, adopt following technical scheme:

A traditional Chinese medicine composition for treating allergic rhinitis, which is composed of honeysuckle extract, isatis root extract, houttuynia cordata extract, borneol and pharmaceutical auxiliary materials.

The honeysuckle extract is chlorogenic acid, the purity of which is not lower than 75%; the further purity is not lower than 78%; the further purity is not lower than 85%.

The preparation method of described honeysuckle extract is:

(1) Extraction: Take honeysuckle, add 10-12 times the amount of water for the first time, soak for 60 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct for 0.5-1 hour , filtered; the combined filtrates were concentrated to a relative density of 1.20 to obtain Honeysuckle Extract 1.

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol and acetone mixed solvent with a weight ratio of 2.5:1 until the ethanol content is 50%-60%, and standing for 24 hours; The supernatant was taken and concentrated to a relative density of 1.30 to obtain the honeysuckle extract 2.

(3) Re-purification: using the honeysuckle extract 2 prepared in step (2) as the starting material, according to the method of step (2), refine for 1-2 times to obtain the honeysuckle extract.

The said Radix isatidis is mainly produced in the southwestern region of my country. Its plant body is called Banlan, also known as Malan. .

The preparation method of described isatidis root extraction is:

(1) Extraction: take Banlangen, add 10-12 times the amount of water for the first time, soak for 30 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct for 0.5-1 hour , filtered; the combined filtrates were concentrated to a relative density of 1.20 to obtain Radix Radix Radix Extract 1.

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol until the amount of ethanol is 75%-80%, standing for 24 hours; taking the supernatant, concentrating to a relative density of 1.30 , to obtain Radix Radix Radix Extract 2.

(3) Re-purification: using the Radix isatidis extract 2 prepared in step (2) as the starting material, and refining for 1-2 times according to the method of step (2), to obtain the Radix isatidis extract.

The preparation method of the Houttuynia cordata extract is:

(1) Extraction: Take Houttuynia cordata, add 8-10 times the amount of water for the first time, soak for 30 minutes, decoct for 1-2 hours, filter; add 7-8 times the amount of water for the second time, decoct for 1- After 1.5 hours, filter; combine the filtrates, concentrate to a relative density of 1.15, and obtain Houttuynia cordata extract 1;

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding acetone until the amount of acetone is 10%-80%, and standing for 24 hours; take the supernatant and concentrate to a relative density of 1.30 , to obtain Houttuynia cordata extract 2;

(3) Re-purification: using the Houttuynia cordata extract 2 prepared in step (2) as the starting material, according to the method of step (2), refine for 1-2 times to obtain the Houttuynia cordata extract.

Further, the weight ratio of the honeysuckle extract, isatis root extract, houttuynia cordata extract, and borneol is (22-25):(11-13):(6-7):1; preferably (22-24 ):(11-12):(6-7):1; more preferably (22.5-23.6):(11.2-11.7):(6.3-6.6):1; more preferably 23.2:11.4:6.5:1.

Further, the pharmaceutical excipient is selected from butyrolactone-modified sodium sulfobutyl-β-cyclodextrin, water, and the penetrant laurocaprazine.

The water is preferably water for injection.

The structural formula of the butyrolactone-modified sodium sulfobutyl-β-cyclodextrin is shown in Figure 1, wherein n is 8-12.

Further, the preparation method of the butyrolactone-modified sodium sulfobutyl-β-cyclodextrin is:

Under N2 protection, add sulfobutyl-β-cyclodextrin, butyrolactone and stannous octoate in N,N-dimethylformamide solvent and mix, heat up to 100°C for 10h, then cool to room temperature, and The reaction mixture was added into diethyl ether, and a precipitate was precipitated, which was recrystallized from absolute ethanol to obtain sodium sulfobutyl-β-cyclodextrin modified with butyrolactone.

Further, the molar ratio of butyrolactone to sulfobutyl-β-cyclodextrin is 15-25:1.

Further, the average molecular weight of the butyrolactone-modified sodium sulfobutyl-β-cyclodextrin is 7000-8500, and the PDI is not more than 1.5, preferably not more than 1.4, more preferably not more than 1.35.

The present invention further provides the application of the above-mentioned traditional Chinese medicine composition for treating rhinitis in the preparation of products for treating allergic rhinitis.

Further, the traditional Chinese medicine composition can be nasal spray, nasal drops and the like.

Further, the present invention provides a preparation method of the above-mentioned Chinese medicine composition for treating rhinitis

(1) Take honeysuckle extract, Radix isatidis extract, and Houttuynia cordata extract, add butyrolactone-modified sulfobutyl-β-cyclodextrin sodium, heat up to 40-50°C, and stir for 1-2 hours until it becomes Add borneol to the clear brown solution; filter (0.45 μm) to obtain Chinese medicine composition liquid 1;

(2) In medicinal liquid 1, add penetrating agent, stir for 25-30 minutes; Add the remaining amount of water for injection; Obtain Chinese medicine composition medicinal liquid 2;

(3) The traditional Chinese medicine composition is bottled to prepare nasal spray and nasal drops.

Compared with the prior art, the present invention has the following beneficial effects:

The present invention adopts butyrolactone-modified sulfobutyl-β-cyclodextrin inclusion insoluble honeysuckle extract, Radix isatidis extract, and Houttuynia cordata extract, which greatly increases the solubility of the above-mentioned extracts and is easy to release and absorb at the same time , to promote drug absorption and improve bioavailability; in addition, borneol is a common aromatic resuscitating drug and adjuvant drug, which has the characteristics of "resuscitating the mind", "the aroma of nature is wandering, and the drug is going up", "going alone is weak, It is suitable for use in combination with other medicines due to the feature of "Adjuvant makes meritorious service". The borneol in the prescription of the present invention can not only promote the absorption of the above three extracts, but also increase the comfort of the nasal spray preparation and effectively treat allergic rhinitis.

Description of drawings

Figure 1: Structural formula of butyrolactone-modified sodium sulfobutyl-β-cyclodextrin.

Detailed ways

The invention discloses a traditional Chinese medicine composition for treating allergic rhinitis composed of honeysuckle, Radix isatidis, Houttuynia cordata and borneol and a preparation method thereof. Those skilled in the art can learn from the contents of the invention and combine the knowledge of pharmaceutical preparations, drug extraction, etc. Relevant principles, appropriate improvement of process parameters to achieve. In particular, it should be pointed out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the scope of the present invention. The application of the present invention has been described through the preferred embodiments, and the relevant personnel can obviously make changes or appropriate changes and combinations to the methods and applications described herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention. Invent technology.

In order to better understand the present invention but not to limit the scope of the present invention, all figures representing dosage, percentage, and other numerical values used in this application should be understood as being modified by the word "about" in all cases. At a minimum, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

The present invention is further described by the following examples, but the examples do not limit the present invention in any way.

Preparation Example 1: Honeysuckle Extract

(1) Extraction: Take honeysuckle, add 10-12 times the amount of water for the first time, soak for 60 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct for 0.5-1 hour , filtered; the combined filtrates were concentrated to a relative density of 1.20 to obtain Honeysuckle Extract 1.

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol and acetone mixed solvent with a weight ratio of 2.5:1 until the ethanol content is 50%-60%, and standing for 24 hours; The supernatant was taken and concentrated to a relative density of 1.30 to obtain the honeysuckle extract 2.

(3) Re-purification: taking the honeysuckle extract 2 prepared in step (2) as the starting material, and refining twice according to the method of step (2), to obtain the honeysuckle extract.

The chlorogenic acid therein was detected, and the content of chlorogenic acid was 82%.

Preparation Example 2: Honeysuckle Extract

(1) Extraction: Take honeysuckle, add 10-12 times the amount of water for the first time, soak for 60 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct for 0.5-1 hour , filtered; the combined filtrates were concentrated to a relative density of 1.20 to obtain Honeysuckle Extract 1.

(2) Refining: take the Radix Radix Radix Extract 1 prepared in step (1) as the starting material, add ethanol until the ethanol content is 50%-60%, and let it stand for 24 hours; take the supernatant and concentrate it to a relative density of 1.30, the honeysuckle extract 2 was obtained.

(3) Re-purification: taking the honeysuckle extract 2 prepared in step (2) as the starting material, and refining twice according to the method of step (2), to obtain the honeysuckle extract.

The chlorogenic acid therein was detected, and the content of chlorogenic acid was 74%.

Preparation Example 3: Radix Radix Radix Extract

(1) Extraction: Take Southern Banlangen (Malan), add 10-12 times the amount of water for the first time, soak for 30 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct Boil for 0.5-1 hour, filter; combine the filtrates, concentrate to a relative density of 1.20, and obtain Radix Radix Radix Extract 1;

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol until the amount of ethanol is 75%-80%, standing for 24 hours; taking the supernatant, concentrating to a relative density of 1.30 , to obtain Radix Radix Radix Extract 2;

(3) Re-purification: using the Radix isatidis extract 2 prepared in step (2) as the starting material, and refining twice according to the method of step (2), to obtain the Radix isatidis extract 3 .

Preparation Example 4: Radix Radix Radix Extract

(1) Extraction: Take Southern Banlangen (Malan), add 10-12 times the amount of water for the first time, soak for 30 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct Boil for 0.5-1 hour, filter; combine the filtrates, concentrate to a relative density of 1.20, and obtain Radix Radix Radix Extract 1;

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol until the amount of ethanol is 75%-80%, standing for 24 hours; taking the supernatant, concentrating to a relative density of 1.30 , to obtain Radix Radix Radix Extract.

Preparation Example 5: Radix Radix Radix Extract

(1) Extraction: take northern isatis root (Isatis indigo), add 10-12 times the amount of water for the first time, soak for 30 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct Boil for 0.5-1 hour, filter; combine the filtrates, concentrate to a relative density of 1.20, and obtain Radix Radix Radix Extract 1;

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol until the amount of ethanol is 75%-80%, standing for 24 hours; taking the supernatant, concentrating to a relative density of 1.30 , to obtain Radix Radix Radix Extract 2;

(3) Re-purification: using the Radix isatidis extract 2 prepared in step (2) as the starting material, and refining twice according to the method of step (2), to obtain the Radix isatidis extract 3 .

Preparation example 6: Houttuynia cordata extract

(1) Extraction: Take Houttuynia cordata, add 8-10 times the amount of water for the first time, soak for 30 minutes, decoct for 1-2 hours, filter; add 7-8 times the amount of water for the second time, decoct for 1- After 1.5 hours, filter; combine the filtrates, concentrate to a relative density of 1.15, and obtain Houttuynia cordata extract 1;

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding acetone until the amount of acetone is 10%-80%, and standing for 24 hours; take the supernatant and concentrate to a relative density of 1.30 , to obtain Houttuynia cordata extract 2;

(3) Re-purification: using the Houttuynia cordata extract 2 prepared in step (2) as the starting material, according to the method of step (2), refine twice to obtain the Houttuynia cordata extract 3 .

Preparation Example 7: Houttuynia cordata extract

(1) Extraction: Take Houttuynia cordata, add 8-10 times the amount of water for the first time, soak for 30 minutes, decoct for 1-2 hours, filter; add 7-8 times the amount of water for the second time, decoct for 1- After 1.5 hours, filter; combine the filtrates, concentrate to a relative density of 1.15, and obtain Houttuynia cordata extract 1;

(2) Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding acetone until the amount of acetone is 10%-80%, and standing for 24 hours; take the supernatant and concentrate to a relative density of 1.30 , to obtain Houttuynia cordata extract 2.

Preparation Example 8: Butyrolactone-modified sodium sulfobutyl-β-cyclodextrin

Under N2 protection, in N,N-dimethylformamide solvent, add sulfobutyl-β-cyclodextrin (21.63g, 10mmol), butyrolactone (13.76g, 160mmol), stannous octoate (0.4mg , 1.0 μmol) were mixed, heated to 100 ° C for 10 h, then cooled to room temperature, the reaction mixture was added to diethyl ether, precipitated, and recrystallized with absolute ethanol to obtain butyrolactone-modified sulfobutyl-β-ring Sodium dextrin.

The average molecular weight by GPC is 8251, and the PDI is 1.31.

Preparation Examples 9-12: Butyrolactone-modified sodium sulfobutyl-β-cyclodextrin.

Butyrolactone addition is the same as the following table, and other preparation methods are the same as Preparation Example 8.

Embodiment 1-5: Chinese medicine composition for the treatment of allergic rhinitis

Preparation:

(1) Take honeysuckle extract, Radix isatidis extract, and Houttuynia cordata extract, add butyrolactone-modified sulfobutyl-β-cyclodextrin sodium, heat up to 40-50°C, and stir for 1-2 hours until it becomes Add borneol to the clear brown solution; filter (0.45 μm) to obtain Chinese medicine composition liquid 1;

(2) Add the penetrant laurocaprazine to the medicinal solution 1, and stir for 25-30 minutes; add the remaining amount of water for injection; obtain the traditional Chinese medicine composition medicinal solution 2;

(3) The traditional Chinese medicine composition is packed into a bottle to prepare a nasal spray.

Embodiment 6-10: Chinese medicinal composition for treating allergic rhinitis

Preparation method: with embodiment 1-5.

Embodiment 11-13: Chinese medicinal composition for treating allergic rhinitis

Preparation method: with embodiment 1-5.

Example 14: Drug efficacy test of the present invention's traditional Chinese medicine composition for treating allergic rhinitis

1. Model preparation and group treatment

Triamcinolone acetonide nasal spray (corticosteroid drugs, produced by Jiangxi Zhenshiming Pharmaceutical Co., Ltd.), ovalbumin (OVA), rat IgE ELISA kit (Nanjing Jiancheng Biotechnology Company), Mucin5AC antibody (abcam company). ,

Rats: 150, half male and half female, weighing 200g ± 30g; after one week of adaptive feeding, 100 rats were randomly selected and treated with ovalbumin OVA sensitization method: intraperitoneal injection of 1mL OVA suspension (containing 0.9% sodium chloride, 20 mg OVA, 30 mg aluminum hydroxide), once every other day, a total of 8 times (15 days) for basic sensitization; on the 16th day, 10% OVA saline solution was instilled into the two front nostrils of the rats, 50 μL on each side , 1 time a day for 10 consecutive days to stimulate allergic rhinitis.

After successful modeling, randomly selected as model group, positive control group, and embodiment 1-13 groups (nasal sprays prepared in embodiment 1-13); 10 animals in each group, and another 10 animals were taken as normal group, and intraperitoneal injection was performed as before. And nasal drops, but the drugs given are all saline.

The normal group and the model group were instilled with physiological saline nasal spray, and the positive control group was instilled with triamcinolone acetonide nasal spray nasal spray. The prepared nasal spray was dripped into the groups of Example 1-10 respectively, and each administration group was given 50 μL. 1 time/day, for 2 consecutive weeks, drop the nostrils on both sides of the rat with a pipette gun.

2. Detection index: detection of serum IgE content

After the rats were anesthetized, the blood was collected from the celiac artery, the serum was separated, and the enzyme-linked immunosorbent assay was carried out according to the kit instructions.

3. Statistical analysis methods

Data processing was carried out by SPSS software, and one-way analysis of variance (One-Way ANOVA) was used for analysis, and the data were expressed as (mean ± standard deviation). P<0.05 means the difference is statistically significant.

4. Results

Detection results of blood IgE content in each group of rats

group 2 weeks after treatment normal group 0.341±0.148 model group 1.117±0.247** positive control group 0.724±0.153# Example 1 group 0.404±0.123##&& Example 2 group 0.417±0.127##&& Example 3 groups 0.421±0.126##&& Embodiment 4 groups 0.431±0.112##& Embodiment 5 groups 0.439±0.116##& Embodiment 6 groups 0.453±0.180##& Embodiment 7 groups 0.464±0.156##& Embodiment 8 groups 0.761±0.121# Embodiment 9 groups 0.807±0.118 Embodiment 10 groups 0.826±0.112 Embodiment 11 groups 0.872±0.115 Embodiment 12 groups 0.853±0.116 Embodiment 13 groups 0,877±0.129

Note: Compared with the normal group, *P<0.05, **P<0.01

Compared with the model group, #P<0.05, ##P<0.01;

Compared with the positive control group, &P<0.05, &&P<0.01

①Compared with the normal group, the content of allergic mediator IgE in the model group increased significantly, and there was a very significant difference between the two (P<0.01), indicating that the model was successfully established.

②Compared with the model group, the nasal sprays prepared in Examples 1-7 can significantly reduce the content of allergic mediator IgE, and all have very significant differences (P<0.01), indicating that the nasal sprays prepared in Examples 1-7 Can treat allergic rhinitis.

Compared with the positive control group, the nasal sprays prepared in Examples 1-7 can significantly reduce the content of allergic mediator IgE, all with very different (P < 0.05) or very significant difference (P < 0.01), illustrating the embodiment 1-7 The prepared spray is better than the corticosteroid drug triamcinolone acetonide (positive control group) in reducing IgE, the main mediator of allergy.

③Compared with the model group, the nasal spray prepared in Example 8 can significantly reduce the content of allergic mediator IgE, and there is a significant difference (P<0.05), indicating that the nasal spray prepared in Example 8 can treat allergic rhinitis .

Compared with the positive control group, the nasal spray prepared in Example 8 can not reduce the content of allergic mediator IgE, and there is no significant difference (P>0.05), indicating that the spray prepared in Example 8 can reduce the main mediator of allergies. IgE is not superior to corticosteroids triamcinolone acetonide (positive control group).

4. Compared with the model group, the nasal sprays prepared in Examples 9-10 can reduce the content of allergic mediator IgE, but there is no significant difference (P>0.05), indicating that the nasal sprays prepared in Examples 9-10 cannot treatment of allergic rhinitis,

Compared with the positive control group, the nasal sprays prepared in Examples 9-10 cannot reduce the content of allergic mediator IgE, and there is no significant difference (P>0.05), indicating that the sprays prepared in Examples 9-10 are reducing IgE, the main mediator of allergy, was not superior to corticosteroid triamcinolone acetonide (positive control group).

4. Compared with the model group, the nasal sprays prepared in Examples 11-13 can reduce the content of allergic mediator IgE, but there is no significant difference (P>0.05), indicating that the nasal sprays prepared in Examples 11-13 cannot treatment of allergic rhinitis,

Compared with the positive control group, the nasal sprays prepared in Examples 11-13 cannot reduce the content of allergic mediator IgE, and there is no significant difference (P>0.05), indicating that the sprays prepared in Examples 11-13 are reducing IgE, the main mediator of allergy, was not superior to corticosteroid triamcinolone acetonide (positive control group).

Analyzing the data in Example 1 and Example 8, the specific South Radix isatidis extract can work synergistically with honeysuckle extract, Houttuynia cordata extract, borneol, etc. to treat allergic rhinitis better, and use the extract prepared from Northern Radix isatidis instead Southern Radix Radix Extract, its therapeutic effects have significant differences. Therefore, the southern Radix Radix extract is preferred in the prescription.

Analyzing Examples 1-5 and Examples 11-13 shows that: honeysuckle extract, Radix isatidis extract, Houttuynia cordata extract, and borneol in specific proportions exert a synergistic effect, and the prepared Chinese medicine composition can effectively treat allergic rhinitis; When lacking any of these components, as in Examples 11-13, the prepared Chinese medicine composition has a very poor effect on treating allergic rhinitis, and compared with the model group, there is no significant difference (P>0.05), so Example 1 11-13 The prepared traditional Chinese medicine composition cannot be used for treating allergic rhinitis.

Example 15: Drug efficacy test of the traditional Chinese medicine composition for treating allergic rhinitis of the present invention after being placed under accelerated conditions for 6 months.

1. Test sample: After placing the nasal spray prepared in Examples 1-7 for 6 months under accelerated conditions (temperature 40°C±2°C, humidity 75%±5%), the drug efficacy was tested.

2, model preparation is the same as embodiment 11, 100 rats, be divided into 10 groups, be randomly model group, positive control group, embodiment 1-7 group (the nasal spray prepared by embodiment 1-7 accelerates placement for 6 months ); 10 rats in each group, another 10 rats were taken as the normal group, intraperitoneal injection and intranasal drip were performed as before, but the drugs given were all normal saline.

The normal group and the model group were instilled with physiological saline nasal spray, and the positive control group was instilled with triamcinolone acetonide nasal spray nasal spray. The prepared nasal spray was dripped into the groups of Example 1-10 respectively, and each administration group was given 50 μL. 1 time/day, for 2 consecutive weeks, drop the nostrils on both sides of the rat with a pipette gun.

3. Detection index and statistical analysis method are the same as in Example 11.

4. Results:

group 2 weeks after treatment normal group 0.347±0.161 model group 1.113±0.235** positive control group 0.727±0.136# Example 1 group 0.398±0.103##&& Example 2 group 0.425±0.125##&& Example 3 groups 0.413±0.134##&& Embodiment 4 groups 0.432±0.116##& Embodiment 5 groups 0.445±0.111##& Embodiment 6 groups 0.823±0.113 Embodiment 7 groups 0.791±0.121

Note: Compared with the normal group, *P<0.05, **P<0.01

Compared with the model group, #P<0.05, ##P<0.01;

Compared with the positive control group, &P<0.05, &&P<0.01

①Compared with the normal group, the content of allergic mediator IgE in the model group increased significantly, and there was a very significant difference between the two (P<0.01), indicating that the model was successfully established.

②Compared with the model group, the nasal sprays prepared in Examples 1-5 can still significantly reduce the content of allergic mediator IgE after 6 months of accelerated placement, all with very significant differences (P<0.01), illustrating that Examples 1-5 5 Stable quality.

Compared with the positive control group, the nasal sprays prepared in Examples 1-5 can still significantly reduce the content of allergic mediator IgE after 6 months of accelerated placement, all with very different (P<0.05) or very significant differences (P<0.05) <0.01), indicating that the quality of the spray prepared in Examples 1-5 is stable.

③Compared with the model group, after 6 months of accelerated placement of the nasal spray prepared in Example 6-7, although it can reduce the content of allergic mediator IgE, there is no significant difference (P>0.05), illustrating that Example 6-7 The prepared nasal spray has poor stability, and the drug effect is significantly reduced after accelerated storage for 6 months.

Compared with the positive control group, the nasal spray prepared in Example 6-7 can not reduce the content of allergic mediator IgE, and there is no significant difference (P>0.05), indicating that the spray prepared in Example 6-7 is stable Poor drug resistance, after 6 months of accelerated placement, the drug effect was significantly reduced.

Analysis of the above data shows that only the honeysuckle extract, southern isatis root extract, Houttuynia cordata extract, and borneol prepared by a specific process, together with a specific modified cyclodextrin, can exert a synergistic effect on each other and effectively treat allergic reactions. rhinitis.

Claims (3)

1. A traditional Chinese medicine composition for treating allergic rhinitis, consisting of honeysuckle extract, isatis root extract, houttuynia cordata extract, borneol, and pharmaceutical excipients; The honeysuckle extract is chlorogenic acid, the purity of which is not less than 75%; The pharmaceutical excipients are sodium sulfobutyl-β-cyclodextrin modified by butyrolactone, water, and the penetrant laurocapram; The weight ratio of the honeysuckle extract, isatis root extract, houttuynia cordata extract, and borneol is 22-24:11-12:6-7:1; The preparation method of described honeysuckle extract is: Extraction: take honeysuckle, add 10-12 times the amount of water for the first time, soak for 60 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct for 0.5-1 hour, filter ; The combined filtrates were concentrated to a relative density of 1.20 to obtain the honeysuckle extract 1; Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding a mixed solvent of ethanol and acetone at a weight ratio of 2.5:1 until the ethanol content is 50%-60%, and standing for 24 hours; take the supernatant solution, concentrated to a relative density of 1.30, to obtain honeysuckle extract 2; Re-refining: using the honeysuckle extract 2 prepared in step (2) as the starting material, according to the method of step (2), refine for 1-2 times to obtain the honeysuckle extract; The said Radix isatidis is produced in Southwest my country, and its plant body is called Radix isatidis, also known as Isatidis; The preparation method of described Radix Radix isatidis extract is: Extraction: Take Banlangen, add 10-12 times the amount of water for the first time, soak for 30 minutes, decoct for 1-1.5 hours, filter; add 8-9 times the amount of water for the second time, decoct for 0.5-1 hour, filter ; The combined filtrates were concentrated to a relative density of 1.20 to obtain Radix Radix Radix Extract 1; Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding ethanol until the amount of ethanol is 75%-80%, and standing for 24 hours; taking the supernatant and concentrating it to a relative density of 1.30 to obtain Radix Radix Radix extract 2; Re-refining: using the isatidis extract 2 prepared in step (2) as the starting material, and refining for 1-2 times according to the method of step (2), to obtain the isatidis extract; The preparation method of the Houttuynia cordata extract is: Extraction: Take Houttuynia cordata, add 8-10 times the amount of water for the first time, soak for 30 minutes, decoct for 1-2 hours, filter; add 7-8 times the amount of water for the second time, decoct for 1-1.5 hours, Filtration; combined filtrates, concentrated to a relative density of 1.15, to obtain Houttuynia cordata extract 1; Refining: using Radix Radix Radix Extract 1 prepared in step (1) as the starting material, adding acetone until the amount of acetone is 10%-80%, and standing for 24 hours; taking the supernatant, concentrating to a relative density of 1.30, and obtaining fish Houttuynia cordata extract 2; Re-refining: using the Houttuynia cordata extract 2 prepared in step (2) as the starting material, according to the method of step (2), refine for 1-2 times to obtain the Houttuynia cordata extract; The average molecular weight of the butyrolactone-modified sodium sulfobutyl-β-cyclodextrin is 7000-8500, and the PDI is not more than 1.35; The preparation method of the butyrolactone-modified sulfobutyl-β-cyclodextrin sodium is as follows: under N2 protection, in N,N-dimethylformamide solvent, add sulfobutyl-β-cyclodextrin Mix alcohol, butyrolactone and stannous octoate, heat up to 100°C and react for 10 hours, then cool to room temperature, add the reaction mixture to diethyl ether, precipitate out, and recrystallize with absolute ethanol to obtain butyrolactone-modified sulfobutyl Sodium beta-cyclodextrin. 2. The traditional Chinese medicine composition according to claim 1, characterized in that: the weight ratio of the honeysuckle extract, Radix isatidis extract, Houttuynia cordata extract, and Borneol is 23.2:11.4:6.5:1. 3. a preparation method of Chinese medicine composition as claimed in claim 1, is characterized in that, preparation method comprises the steps: Take honeysuckle extract, Radix isatidis extract, and Houttuynia cordata extract, add butyrolactone-modified sulfobutyl-β-cyclodextrin sodium, heat up to 40-50°C, and stir for 1-2 hours until it turns into a clear brown color solution, add borneol; filter 0.45 μm to obtain Chinese medicine composition liquid 1; In the medicinal solution 1, add the penetrating agent and stir for 25-30 minutes; add the remaining amount of water for injection; obtain the traditional Chinese medicine composition medicinal solution 2; The traditional Chinese medicine composition is packed into a bottle to prepare nasal spray and nasal drops.

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