A composite traditional Chinese medicine composition, a preparation method thereof and application thereof in preparing a medicine for treating allergic rhinitis

Abstract

This invention provides a compound traditional Chinese medicine composition, its preparation method, and its application in the preparation of drugs for treating allergic rhinitis, belonging to the field of traditional Chinese medicine technology. The compound traditional Chinese medicine composition of this invention includes: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, Calculus bovis, Borneol, and Mentha haplocalyx. Antrodia camphorata, the principal ingredient, fundamentally regulates immunity and reduces inflammation and swelling. Paeonia suffruticosa, Cynanchum paniculatum, and Cicadae periostracum assist in anti-allergy and clearing heat and wind. Calculus bovis and Borneol are adjuvant ingredients that resolve phlegm, open the orifices, clear heat, and relieve pain. Mentha haplocalyx guides the medicine upwards and relieves local symptoms. This invention treats allergic rhinitis using a combination of internal and external application. Internal administration exerts a systemic regulatory effect and enhances immunity, while external application to the nose quickly relieves symptoms. The comprehensive formula addresses both the root cause and symptoms, with the various drug components synergistically enhancing anti-inflammatory, anti-allergic, and immunomodulatory effects to achieve the therapeutic effect of treating allergic rhinitis.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a compound traditional Chinese medicine composition, its preparation method, and its application in the preparation of drugs for treating allergic rhinitis. Background Technology

[0002] Allergic rhinitis (AR), also known as allergic rhinitis, is a non-infectious inflammatory disease of the nasal mucosa primarily mediated by IgE. Clinically, it mainly manifests as nasal itching, sneezing, nasal congestion, and clear, watery nasal discharge. Allergic rhinitis not only affects patients' quality of life but can also lead to other complications such as sinusitis, otitis media, and asthma. In severe cases, it can even affect a patient's sleep, learning, and work efficiency. Currently, clinical treatments for allergic rhinitis mainly include drug therapy, immunotherapy, and surgical treatment.

[0003] Currently, drug therapy is the main treatment for allergic rhinitis, with commonly used Western medicines including antihistamines, corticosteroids, and decongestants. While these medications can relieve symptoms to some extent, they often have side effects. For example, antihistamines may cause adverse reactions such as drowsiness and dry mouth, affecting patients' daily lives and work; long-term use of corticosteroids may lead to local or systemic adverse reactions, such as nasal dryness, nosebleeds, and osteoporosis; and improper use of decongestants may cause drug-induced rhinitis, worsening the condition. Therefore, finding a safe, effective treatment method with few side effects has become an important issue for the medical community.

[0004] Traditional Chinese medicine (TCM) has a long history and unique advantages in treating allergic rhinitis, with relatively few side effects and good patient tolerance. However, most TCM prescriptions currently used in clinical practice are empirical formulas, lacking scientific experimental verification, and their efficacy and safety need further improvement. Therefore, developing a safe, effective TCM composition with few side effects for treating allergic rhinitis has significant clinical and social value. Summary of the Invention

[0005] The purpose of this invention is to provide a compound traditional Chinese medicine composition, its preparation method, and its application in the preparation of a drug for treating allergic rhinitis. The drug is administered orally and applied topically to treat allergic rhinitis. The oral administration exerts a systemic regulatory effect and improves immunity, while the topical application to the nose quickly relieves symptoms and has a significant therapeutic effect.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a compound traditional Chinese medicine composition for treating allergic rhinitis, comprising the following raw materials in parts by weight: 20-30 parts of Antrodia camphorata, 10-20 parts of Paeonia suffruticosa, 5-10 parts of Cynanchum paniculatum, 5-10 parts of Cicadae periostracum, 1-3 parts of Calculus bovis, 0.5-1 part of Borneol, and 5-10 parts of Mentha haplocalyx.

[0008] The present invention also provides the application of the above-mentioned compound traditional Chinese medicine composition in the preparation of drugs for treating allergic rhinitis.

[0009] Preferably, the dosage form of the drug is a decoction, pill, powder, granule, capsule, tablet, oral liquid, ointment, syrup, spray, or gel.

[0010] More preferably, the preparation method of the spray includes: drying and pulverizing Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx, adding ethanol solution, ultrasonically soaking, reflux extraction, filtering, vacuum concentration, and drying to obtain traditional Chinese medicine powder; incorporating borneol with β-cyclodextrin, drying and pulverizing to obtain borneol-β-CD inclusion complex; pulverizing bezoar, mixing it with traditional Chinese medicine powder, borneol-β-CD inclusion complex, solvent, isotonicity regulator, thickener, preservative, antioxidant, and water, and filtering to obtain the spray.

[0011] More preferably, the volume percentage of the ethanol solution is 60%-70%, the ultrasonic immersion power is 200-300W, the frequency is 20-30kHz, and the time is 25-35min.

[0012] More preferably, the material-to-liquid ratio of the reflux extraction is 1:8-10 g / mL, the temperature is 70-80℃, the extraction is performed 1-3 times, and each extraction lasts 40-60 minutes.

[0013] Preferably, the preparation method of the granules includes: drying and pulverizing Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx, mixing with water, sequentially adding xylanase, β-glucosidase, and fig protease for ultrasonic enzymatic hydrolysis, filtering to obtain the hydrolysate, adding glucose, inoculating with compound microorganisms for anaerobic fermentation, filtering to obtain the fermentation broth, concentrating under reduced pressure, and spray drying to obtain fermented dry extract powder; incorporating borneol with β-cyclodextrin, drying, and pulverizing to obtain borneol-β-CD inclusion complex; pulverizing bezoar, mixing it with fermented dry extract powder, borneol-β-CD inclusion complex, filler, disintegrant, lubricant, and flavoring agent, and granulating to obtain the granules.

[0014] More preferably, the amount of xylanase added is 0.3%-0.8% of the total mass of Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; the enzymatic hydrolysis temperature is 40-50℃; the pH value is 4-6; the ultrasonic power is 200-300W; the frequency is 20-30kHz; and the time is 1-3h. The amount of β-glucosidase added is 2%-5% of the total mass of Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; and the enzymatic hydrolysis temperature is 40-50℃; The enzymatic hydrolysis was performed at 50℃, pH 5-6, ultrasonic power 200-300W, frequency 20-30kHz, and time 40-60min; the amount of fig protease added was 0.2%-0.5% of the total mass of Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; the enzymatic hydrolysis temperature was 37-40℃, pH 7-8, ultrasonic power 200-300W, frequency 20-30kHz, and time 30-40min.

[0015] More preferably, the inclusion complex comprises: dissolving β-cyclodextrin in water to obtain an aqueous solution of β-cyclodextrin, dissolving borneol in anhydrous ethanol to obtain an ethanol solution of borneol, slowly adding the ethanol solution of borneol to the aqueous solution of β-cyclodextrin, stirring in a water bath at 35-45°C for 1-2 hours, allowing it to stand and precipitate, filtering, and drying the precipitate to obtain the borneol-β-CD inclusion complex.

[0016] More preferably, the fermentation compound microorganisms consist of Bifidobacterium animalis subsp. lactis and Lactobacillus digestans in a weight ratio of 1-3:2-5. The amount of compound microorganisms added is 0.8%-1.2% of the total mass of Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx. The fermentation temperature is 35-40℃, the pH value is 6-7, and the time is 24-72h.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] This invention provides a compound traditional Chinese medicine composition for treating allergic rhinitis, comprising: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, Calculus bovis, Borneol, and Mentha haplocalyx. Antrodia camphorata, the principal ingredient, fundamentally regulates immunity and reduces inflammation and swelling. Paeonia suffruticosa, Cynanchum paniculatum, and Cicadae periostracum assist in anti-allergy and clearing heat and wind. Calculus bovis and Borneol are adjuvants for resolving phlegm, opening the nasal passages, clearing heat, and relieving pain. Mentha haplocalyx guides the medicine upwards and alleviates local symptoms. This compound traditional Chinese medicine composition treats allergic rhinitis using a combination of oral and topical application. Oral administration exerts a systemic regulatory effect, enhancing immunity, while topical application directly targets the nasal area, rapidly relieving allergic rhinitis symptoms. The formula addresses both the root cause and symptoms, with each ingredient synergistically enhancing anti-inflammatory, anti-allergic, and immunomodulatory effects, while simultaneously relieving symptoms such as nasal congestion, nasal itching, sneezing, and runny nose through various pathways. This compound traditional Chinese medicine composition consists entirely of natural herbs with few side effects, suitable for long-term use, and especially suitable for patients intolerant to or prone to developing drug resistance to Western medicine. Detailed Implementation

[0019] This invention provides a compound traditional Chinese medicine composition for treating allergic rhinitis, comprising the following raw materials in parts by weight: 20-30 parts of Antrodia camphorata, 10-20 parts of Paeonia suffruticosa, 5-10 parts of Cynanchum paniculatum, 5-10 parts of Cicadae periostracum, 1-3 parts of Calculus bovis, 0.5-1 part of Borneol, and 5-10 parts of Mentha haplocalyx.

[0020] The present invention also provides the application of the above-mentioned compound traditional Chinese medicine composition in the preparation of drugs for treating allergic rhinitis.

[0021] The principal, assistant, adjuvant, and guiding relationships of the compound traditional Chinese medicine composition described in this invention are as follows:

[0022] Principal ingredient: Antrodia camphorata

[0023] Antrodia camphorata is the principal ingredient in this formula, possessing the functions of clearing heat and detoxifying, anti-inflammatory and swelling-reducing, and regulating immunity. Modern research shows that the triterpenoids and polysaccharides in Antrodia camphorata can significantly inhibit the release of inflammatory mediators, reduce the inflammatory response of the nasal mucosa, and enhance the body's immunity, thus fundamentally alleviating the symptoms of allergic rhinitis. As the principal ingredient, Antrodia camphorata plays a leading role in the formula, treating the core pathogenesis of allergic rhinitis (deficiency of lung, spleen, and kidney, and invasion of external pathogens).

[0024] Assistant herbs: Moutan bark, Cynanchum paniculatum, Cicada slough

[0025] Moutan bark has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis, and anti-allergy. Its active ingredient, paeonol, can inhibit histamine release, reduce nasal congestion and edema, and relieve symptoms such as nasal congestion and runny nose. As an adjuvant, moutan bark assists Antrodia camphorata in enhancing its anti-inflammatory and anti-allergic effects.

[0026] Xu Changqing (Radix Cynanchi Aristolochiae) possesses the effects of dispelling wind and relieving itching, anti-allergy, and clearing heat and detoxifying. Its active ingredient, paeonol, inhibits the release of inflammatory mediators, relieving nasal congestion and increased secretions. As an adjuvant, it can enhance the immunity and anti-inflammatory effects of Antrodia camphorata, while also improving nasal symptoms (such as nasal congestion, nasal itching, and runny nose).

[0027] Cicada molting has the effects of dispelling wind and clearing heat, relieving lung congestion and soothing the throat, and anti-allergy. The active ingredients in cicada molting can inhibit mast cell degranulation and reduce the release of inflammatory mediators, thereby alleviating symptoms such as nasal itching and sneezing. As an auxiliary ingredient, cicada molting works synergistically with paeonol to enhance the therapeutic effect of the principal ingredient.

[0028] Adjuvant herbs: bezoar, borneol

[0029] Calculus bovis has the effects of clearing heat and detoxifying, resolving phlegm and opening the nasal passages. The bile acid components in calculus bovis can inhibit inflammatory responses and reduce swelling of the nasal mucosa and increased secretions. As an adjuvant, calculus bovis assists the principal and assistant drugs in treating the concurrent symptoms of allergic rhinitis (such as phlegm-dampness obstruction and nasal congestion), while enhancing the anti-inflammatory effect of the prescription.

[0030] Borneol has the effects of clearing the mind, relieving fever, and alleviating pain. It can quickly penetrate the nasal mucosa to relieve symptoms such as nasal congestion and headache. As an adjuvant, borneol assists the principal and assistant drugs in improving local symptoms, while also enhancing drug permeability and bioavailability.

[0031] Used as a medicinal ingredient: peppermint

[0032] Peppermint has the effects of dispelling wind and heat, clearing the head and eyes, and relieving rashes and itching. Menthol in peppermint can stimulate the vasoconstriction of the nasal mucosa, relieving nasal congestion, and also has a cooling and antipruritic effect, alleviating nasal itching and sneezing. As an adjuvant, peppermint guides other medicines directly to the affected area in the nose, while also harmonizing the other medicines and enhancing the overall efficacy of the prescription.

[0033] The compound traditional Chinese medicine composition of the present invention has the following advantages:

[0034] Treating both the symptoms and the root cause: The principal ingredient, Antrodia camphorata, fundamentally regulates immunity and reduces inflammation and swelling. The assistant ingredients, Paeonia suffruticosa, Cynanchum paniculatum, and Cicadae periostracum, assist in anti-allergy and clearing heat and wind. The adjuvant ingredients, Calculus bovis and Borneol, resolve phlegm, open the orifices, clear heat, and relieve pain. The guiding ingredient, Mentha haplocalyx, guides the medicine upward and relieves local symptoms. The whole formula treats both the symptoms and the root cause, relieving symptoms and regulating the body's constitution. Synergistic effect: The various drug components work together to enhance the anti-inflammatory, anti-allergic, and immune-regulating effects, while relieving symptoms such as nasal congestion, nasal itching, sneezing, and runny nose through different pathways. High safety: All the drugs in the formula are natural Chinese medicines with few side effects, suitable for long-term use, especially for patients who are intolerant to or prone to developing drug resistance to Western medicine.

[0035] The preferred dosage form of the drug described in this invention is decoction, pill, powder, granule, capsule, tablet, oral liquid, ointment, syrup, spray, or gel.

[0036] The preferred preparation method of the spray of the present invention includes: drying and pulverizing Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx, adding ethanol solution, ultrasonically soaking, reflux extraction, filtering, vacuum concentration, and drying to obtain traditional Chinese medicine powder; incorporating borneol with β-cyclodextrin, drying and pulverizing to obtain borneol-β-CD inclusion complex; pulverizing bezoar, mixing it with traditional Chinese medicine powder, borneol-β-CD inclusion complex, solvent, isotonicity regulator, thickener, preservative, antioxidant, and water, and filtering to obtain the spray.

[0037] The preferred particle size for pulverizing in this invention is 100-200 mesh, more preferably 150 mesh. This invention increases the surface area of ​​pulverized Chinese herbal medicines, improves extraction efficiency, disrupts cell structure, facilitates component dissolution, results in more uniform extraction, saves extraction solvent and time, and improves subsequent extraction effects.

[0038] The volume percentage of the ethanol solution described in this invention is preferably 60%-70%, more preferably 65%. The ultrasonic soaking power is preferably 200-300W, more preferably 250W, the frequency is preferably 20-30kHz, more preferably 25kHz, and the time is 25-35min, more preferably 30min. By ultrasonically soaking the traditional Chinese medicine in ethanol before extraction, the cell nodes are disrupted, allowing the ethanol to contact the active ingredients in the medicinal material more quickly, thus accelerating the selective dissolution of the active ingredients from the cells and shortening the extraction time.

[0039] The preferred material-to-liquid ratio for the reflux extraction described in this invention is 1:8-10 g / mL, more preferably 1:9 g / mL; the preferred temperature is 70-80℃, more preferably 75℃; the preferred number of extractions is 1-3 times, more preferably 2 times; and each extraction is preferably 40-60 min, more preferably 50 min. This step can disrupt the cell structure, breaking the cell's binding and allowing the active ingredients to fully dissolve. Ethanol molecules can penetrate into the medicinal material more quickly, making full contact with the active ingredients, greatly improving the dissolution rate of the active ingredients, increasing the solubility of the active ingredients in ethanol, shortening the extraction time, improving extraction efficiency, and enhancing the purity and quality of the extract.

[0040] The solvents used in this invention are preferably ethanol and 1,2-propanediol, the isotonicity regulator is preferably sodium chloride or glucose, the thickener is preferably hydroxypropyl methylcellulose, the preservative is preferably benzalkonium chloride, and the antioxidant is preferably EDTA-2Na. The preferred mass ratio of the herbal powder, solvent, isotonicity regulator, thickener, preservative, antioxidant, and water is 1-3:15-25:0.9:0.1-0.3:0.01-0.03:60-85, more preferably 2:20:0.9:0.2:0.02:76.88.

[0041] The method of using the spray of this invention is as follows: blow your nose to clear nasal secretions and keep your nasal cavity clear. Shake the spray well, keep your head upright or tilted slightly forward, and gently insert the nozzle into the nostril (about 0.5 cm), aiming at the outer wall of the nasal cavity (not the nasal septum). Press the nozzle while gently inhaling to distribute the spray evenly on the nasal mucosa. Spray 1-2 times in each nostril, 3 times a day.

[0042] The externally applicable dosage forms of this invention are ointments, sprays, and gels. The three have the same active ingredient, which is a traditional Chinese medicine composition (traditional Chinese medicine powder, borneol-β-CD inclusion complex, and bezoar). The excipients vary depending on the dosage form.

[0043] The ointment of the present invention is preferably an ointment, and the preparation method of the ointment preferably includes: mixing white petrolatum, octadecanol and glyceryl monostearate, heating and melting to obtain an oil phase; mixing glycerol with water to obtain an aqueous phase, adding the oil phase and stirring to form a homogeneous emulsion, and mixing with the traditional Chinese medicine composition to obtain the ointment.

[0044] The preferred method for preparing the gelling agent of the present invention includes: adding carbomer 940 to water to fully swell, adding triethanolamine to adjust the pH value to 7, forming a transparent gel, and mixing it with the traditional Chinese medicine composition to obtain the gelling agent.

[0045] The preferred method for preparing the granules of the present invention includes: drying and pulverizing Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx, mixing with water, sequentially adding xylanase, β-glucosidase, and fig protease for ultrasonic enzymatic hydrolysis, filtering to obtain the hydrolysate, adding glucose, inoculating with compound microorganisms for anaerobic fermentation, filtering to obtain the fermentation broth, concentrating under reduced pressure, and spray drying to obtain fermented dry extract powder; incorporating borneol with β-cyclodextrin, drying, and pulverizing to obtain borneol-β-CD inclusion complex; pulverizing bezoar, mixing with fermented dry extract powder, borneol-β-CD inclusion complex, filler, disintegrant, lubricant, and flavoring agent, and granulating to obtain the granules.

[0046] The xylanase used in this invention was purchased from Jiangsu Madden Biotechnology Co., Ltd., catalog number 02144, with an enzyme activity of 100,000 U / g; the β-glucosidase was purchased from Xi'an Zebang Biotechnology Co., Ltd., catalog number zb-6415, with an enzyme activity of 5,000 U / g; and the fig protease was purchased from Jiangsu Huace Biotechnology Co., Ltd., catalog number 0, with an enzyme activity of 100,000 U / g. The preferred amount of xylanase added in this invention is 0.3%-0.8% of the total mass of the *Antrodia camphorata*, *Paeonia suffruticosa*, *Cynanchum paniculatum*, cicada slough, and peppermint, more preferably 0.5%. The preferred enzymatic hydrolysis temperature is 40-50℃, more preferably 45℃. The preferred pH value is 4-6, more preferably 5. The preferred ultrasonic power is 200-300W, more preferably 250W. The preferred frequency is 20-30kHz, more preferably 25kHz. The preferred time is 1-3h, more preferably 2h. The preferred amount of β-glucosidase added is 2%-5% of the total mass of the *Antrodia camphorata*, *Paeonia suffruticosa*, *Cynanchum paniculatum*, cicada slough, and peppermint, more preferably 3%. The preferred enzymatic hydrolysis temperature is 40-50℃, more preferably 45℃. The preferred pH value is 5-6, more preferably... The preferred ultrasonic power is 200-300W, more preferably 250W; the preferred frequency is 20-30kHz, more preferably 25kHz; and the preferred time is 40-60min, more preferably 50min. The amount of fig protease added is preferably 0.2%-0.5% of the total mass of the *Antrodia camphorata*, *Paeonia suffruticosa*, *Cynanchum paniculatum*, *Cicada slough*, and *Mentha haplocalyx*, more preferably 0.4%. The preferred enzymatic hydrolysis temperature is 37-40℃, more preferably 38℃; the preferred pH value is 7-8, more preferably 7.5; the preferred ultrasonic power is 200-300W, more preferably 250W; the preferred frequency is 20-30kHz, more preferably 25kHz; and the preferred time is 30-40min, more preferably 35min. In this step, the cavitation and mechanical vibration effects of the ultrasound can accelerate the contact between enzyme molecules and the substrate (medicinal components), enhance enzyme activity, and increase the rate of the enzymatic hydrolysis reaction. Meanwhile, ultrasound can further promote the penetration of solvents into medicinal materials, as well as the dissolution and diffusion of active ingredients, making the enzymatic hydrolysis process more thorough and efficient.

[0047] The inclusion complex of the present invention preferably comprises: dissolving β-cyclodextrin in water to obtain an aqueous solution of β-cyclodextrin; dissolving borneol in anhydrous ethanol to obtain an ethanol solution of borneol; slowly adding the ethanol solution of borneol dropwise to the aqueous solution of β-cyclodextrin; stirring in a water bath at 35-45°C for 1-2 hours; allowing to stand and precipitate; filtering; and drying the precipitate to obtain the borneol-β-CD inclusion complex. This inclusion complex can improve the solubility of borneol, reduce volatility loss, improve stability and bioavailability, and, when used externally, reduce irritation to sensitive tissues such as the nasal cavity and eyes, thus improving patient tolerance.

[0048] The fermentation complex microorganisms described in this invention are preferably composed of *Bifidobacterium animalis* subsp. *lactis* and *Companilactobacillus alimentarius* in a weight ratio of 1-3:2-5, with a more preferred weight ratio of 2:4. Both *Bifidobacterium animalis* subsp. *lactis* and *Companilactobacillus alimentarius* were purchased from the China Industrial Microbial Culture Collection Center. *Bifidobacterium animalis* subsp. *lactis* CI CC21712 had a viable count of 3 billion CFU / g, and *Companilactobacillus alimentarius* CICC 6284 had a viable count of 1.5 billion CFU / g. The preferred amount of the compound microorganisms added is 0.8%-1.2% of the total mass of Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx, more preferably 1%. The preferred amount of glucose added is 1%-3% of the mass of the enzymatic hydrolysate, more preferably 2%. The preferred fermentation temperature is 35-40℃, more preferably 37℃. The preferred pH value is 6-7, more preferably 6.5. The preferred fermentation time is 24-72 hours, more preferably 36 hours. The present invention exhibits a synergistic effect between Bifidobacterium animalis subsp. lactis and Lactobacillus digestica-associated with digestion. The combined use of these two in the fermentation of Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx can improve the extraction rate and bioavailability of the active ingredients, transforming and modifying the components of the traditional Chinese medicine, thereby enhancing its efficacy in treating allergic rhinitis.

[0049] The filler preferred in this invention is lactose or microcrystalline cellulose, the disintegrant preferred is sodium carboxymethyl starch, the lubricant preferred is magnesium stearate, and the flavoring agent preferred is steviol glycosides. The preferred mass ratio of bezoar, filler, disintegrant, lubricant, and flavoring agent is 1-3:25-45:3-6:0.3-0.8:0.3-0.8, more preferably 3:35:5:0.5:0.5.

[0050] The method of using the granules of this invention is as follows: Adults take 5g each time, 3 times a day, dissolved in warm water.

[0051] In this invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0052] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0053] Unless otherwise specified, the following embodiments are all conventional methods.

[0054] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0055] Example 1

[0056] Preparation of Compound Traditional Chinese Medicine Composition - Spray

[0057] (1) Weighing: Weigh 25 parts by weight of Antrodia camphorata, 15 parts by weight of Paeonia suffruticosa, 8 parts by weight of Cynanchum paniculatum, 8 parts by weight of Cicadae periostracum, 2 parts by weight of Calculus bovis, 0.8 parts by weight of Borneol and 8 parts by weight of Mentha haplocalyx.

[0058] (2) Ethanol extraction: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx were dried, pulverized and passed through a 150-mesh sieve and then mixed. An ethanol solution with a volume percentage of 65% was added at a material-to-liquid ratio of 1:9 g / mL. The mixture was ultrasonically soaked for 30 min at 250 W and 25 kHz to obtain an ultrasonic mixture. The mixture was then transferred to a reflux extraction device and refluxed twice at 75 °C for 50 min each time. The mixture was filtered, the filtrates were combined, concentrated under reduced pressure, and spray-dried to a water content of 3% to obtain Chinese herbal powder.

[0059] (3) Inclusion: β-cyclodextrin was added to purified water and stirred at 65°C until completely dissolved to obtain an aqueous solution of β-cyclodextrin. Borneol was dissolved in anhydrous ethanol to obtain an ethanol solution of borneol. The ethanol solution of borneol was slowly added dropwise to the aqueous solution of β-cyclodextrin (while stirring) to obtain a mixture. The mixture was magnetically stirred at 400 rpm for 1.5 h in a constant temperature water bath at 40°C, cooled to room temperature, stirred for another h, and allowed to stand at 4°C for 12 h. The mixture was then filtered, the precipitate was collected, dried at 40°C to a water content of 4%, and pulverized through a 100-mesh sieve to obtain the borneol-β-CD inclusion complex. The concentration of β-cyclodextrin in the aqueous solution of β-cyclodextrin was 35 mg / mL, the concentration of borneol in the ethanol solution of borneol was 50 mg / mL, and the volume ratio of the aqueous solution of β-cyclodextrin to the ethanol solution of borneol was 10:1.

[0060] (4) Spray preparation: Hydroxypropyl methylcellulose was fully swollen by mixing with purified water, and then mixed with traditional Chinese medicine powder, borneol-β-CD inclusion complex, bezoar (crushed and passed through a 500-mesh sieve), anhydrous ethanol, 1,2-propanediol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water. The mixture was stirred at 300 rpm for 60 min to obtain the spray. The weight ratio of traditional Chinese medicine powder, anhydrous ethanol, 1,2-propanediol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water (total) was 2:12:8:0.9:0.2:0.02:76.88.

[0061] Example 2

[0062] Preparation of Compound Traditional Chinese Medicine Composition - Spray

[0063] (1) Weighing: Weigh 20 parts by weight of Antrodia camphorata, 10 parts by weight of Paeonia suffruticosa, 5 parts by weight of Cynanchum paniculatum, 5 parts by weight of Cicadae periostracum, 1 part by weight of Calculus bovis, 0.5 parts by weight of Borneol and 5 parts by weight of Mentha haplocalyx.

[0064] (2) Ethanol extraction: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx were dried, pulverized and passed through a 100-mesh sieve and then mixed. An ethanol solution with a volume percentage of 60% was added at a material-liquid ratio of 1:8 g / mL. The mixture was ultrasonically soaked for 35 min at 200 W and 20 kHz to obtain an ultrasonic mixture. The mixture was then transferred to a reflux extraction device and refluxed at 80 °C for 60 min. After filtration, the filtrate was concentrated under reduced pressure and spray-dried to a water content of 4% to obtain Chinese herbal powder.

[0065] (3) Inclusion: β-cyclodextrin was added to purified water and stirred at 60°C until completely dissolved to obtain an aqueous solution of β-cyclodextrin. Borneol was dissolved in anhydrous ethanol to obtain an ethanol solution of borneol. The ethanol solution of borneol was slowly added dropwise to the aqueous solution of β-cyclodextrin (while stirring) to obtain a mixture. The mixture was magnetically stirred at 300 rpm for 2 h in a constant temperature water bath at 38°C, cooled to room temperature, stirred for another 1 h, and allowed to stand at 4°C for 12 h. The mixture was then filtered, the precipitate was collected, dried at 38°C to a water content of 4%, and pulverized through a 100-mesh sieve to obtain the borneol-β-CD inclusion complex. The concentration of β-cyclodextrin in the aqueous solution of β-cyclodextrin was 30 mg / mL, the concentration of borneol in the ethanol solution of borneol was 45 mg / mL, and the volume ratio of the aqueous solution of β-cyclodextrin to the ethanol solution of borneol was 10:1.

[0066] (4) Spray preparation: Hydroxypropyl methylcellulose was fully swollen by mixing with purified water, and then mixed with traditional Chinese medicine powder, borneol-β-CD inclusion complex, bezoar (crushed and passed through a 400-mesh sieve), anhydrous ethanol, 1,2-propanediol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water. The mixture was stirred at 250 rpm for 90 min to obtain the spray. The weight ratio of traditional Chinese medicine powder, anhydrous ethanol, 1,2-propanediol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water (total) was 1:10:5:0.9:0.1:0.01:82.99.

[0067] Example 3

[0068] Preparation of Compound Traditional Chinese Medicine Composition - Spray

[0069] (1) Weighing: Weigh 30 parts of Antrodia camphorata, 20 parts of Paeonia suffruticosa, 10 parts of Cynanchum paniculatum, 10 parts of Cicadae periostracum, 3 parts of Calculus bovis, 1 part of Borneol and 10 parts of Mentha haplocalyx.

[0070] (2) Ethanol extraction: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx were dried, pulverized and passed through a 200-mesh sieve and then mixed. An ethanol solution with a volume percentage of 70% was added at a material-to-liquid ratio of 1:10 g / mL. The mixture was ultrasonically soaked for 25 min at 300 W and 30 kHz to obtain an ultrasonic mixture. The mixture was then transferred to a reflux extraction device and refluxed for 3 times at 70 °C for 40 min each time. The mixture was filtered, the filtrates were combined, concentrated under reduced pressure, and spray-dried to a water content of 2% to obtain Chinese herbal powder.

[0071] (3) Inclusion: β-cyclodextrin was added to purified water and stirred at 70°C until completely dissolved to obtain β-cyclodextrin aqueous solution. Borneol was dissolved in anhydrous ethanol to obtain borneol ethanol solution. Borneol ethanol solution was slowly added dropwise to β-cyclodextrin aqueous solution (while stirring) to obtain a mixture. The mixture was magnetically stirred at 430 rpm for 1 h in a constant temperature water bath at 42°C, cooled to room temperature, stirred for another 1 h, and allowed to stand at 4°C for 12 h. The mixture was then filtered, the precipitate was collected, dried at 42°C to a water content of 3%, and pulverized through a 100-mesh sieve to obtain borneol-β-CD inclusion complex. The concentration of β-cyclodextrin in the β-cyclodextrin aqueous solution was 32 mg / mL, the concentration of borneol in the borneol ethanol solution was 48 mg / mL, and the volume ratio of the β-cyclodextrin aqueous solution to the borneol ethanol solution was 10:1.

[0072] (4) Spray preparation: Hydroxypropyl methylcellulose was fully swollen by mixing with purified water, and then mixed with traditional Chinese medicine powder, borneol-β-CD inclusion complex, bezoar (crushed and passed through a 600-mesh sieve), anhydrous ethanol, 1,2-propanediol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water. The mixture was stirred at 350 rpm for 50 min to obtain the spray. The weight ratio of traditional Chinese medicine powder, anhydrous ethanol, 1,2-propanediol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water (total) was 3:15:10:0.9:0.3:0.03:70.77.

[0073] Example 4

[0074] Preparation of Compound Traditional Chinese Medicine Composition - Granules

[0075] (1) Weighing: Weigh 28 parts by weight of Antrodia camphorata, 18 parts by weight of Paeonia suffruticosa, 7 parts by weight of Cynanchum paniculatum, 7 parts by weight of Cicadae periostracum, 2 parts by weight of Calculus bovis, 0.7 parts by weight of Borneol and 7 parts by weight of Mentha haplocalyx.

[0076] (2) Enzymatic hydrolysis: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx were dried, pulverized and passed through a 150-mesh sieve, and mixed with purified water (material-to-liquid ratio of 1:10 g / mL). Xylanase was added and enzymatically hydrolyzed by sonication at 45℃, pH 5, 250W and 25kHz for 2 hours. The enzyme was inactivated at 85℃ for 15 minutes. β-glucosidase was added and enzymatically hydrolyzed by sonication at 45℃, pH 5.5, 250W and 25kHz for 50 minutes. The enzyme was inactivated at 85℃ for 15 minutes. Figinase was added and enzymatically hydrolyzed by sonication at 38℃, pH 7.5, 250W and 25kHz for 35 minutes. The enzyme was inactivated at 85℃ for 10 minutes. The mixture was filtered to obtain the enzymatic hydrolysate.

[0077] The amount of xylanase added is 0.5% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; the amount of β-glucosidase added is 3% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; and the amount of fig protease added is 0.4% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx.

[0078] (3) Fermentation: After adding glucose to the enzymatic hydrolysate, inoculate with compound microorganisms and anaerobic ferment for 36 h at 37 °C and pH 6.5, sterilize at 85 °C for 15 min, centrifuge at 3000 rpm for 15 min, take the supernatant, concentrate under reduced pressure, and spray dry to 4% water content to obtain fermented dry extract powder.

[0079] The amount of glucose added is 2% of the mass of the enzymatic hydrolysate; the compound microorganism is composed of Bifidobacterium animalis subsp. lactis and Lactobacillus digestans in a weight ratio of 2:4, and the inoculation amount of the compound microorganism is 1%.

[0080] (4) Inclusion: β-cyclodextrin was added to purified water and stirred at 65°C until completely dissolved to obtain an aqueous solution of β-cyclodextrin. Borneol was dissolved in anhydrous ethanol to obtain an ethanol solution of borneol. The ethanol solution of borneol was slowly added dropwise to the aqueous solution of β-cyclodextrin (while stirring) to obtain a mixture. The mixture was magnetically stirred at 400 rpm for 1.5 h in a constant temperature water bath at 40°C, cooled to room temperature, stirred for another h, and allowed to stand at 4°C for 12 h. The mixture was then filtered, the precipitate was collected, dried at 40°C to a water content of 4%, and pulverized through a 100-mesh sieve to obtain the borneol-β-CD inclusion complex. The concentration of β-cyclodextrin in the aqueous solution of β-cyclodextrin was 35 mg / mL, the concentration of borneol in the ethanol solution of borneol was 50 mg / mL, and the volume ratio of the aqueous solution of β-cyclodextrin to the ethanol solution of borneol was 10:1.

[0081] (5) Granule preparation: The bezoar is pulverized and passed through a 500-mesh sieve, and mixed with fermented dry extract powder, borneol-β-CD inclusion complex, lactose, microcrystalline cellulose, sodium carboxymethyl starch, and steviol glycosides to obtain a mixture. A 70% volume percentage ethanol solution is added, and the mixture is granulated and sized. Magnesium stearate is added and mixed to obtain granules. The weight ratio of bezoar, lactose, microcrystalline cellulose, sodium carboxymethyl starch, steviol glycosides, and magnesium stearate is 2:20:15:5:0.5:0.5. The amount of ethanol solution added is 18% of the mass of the mixture.

[0082] Example 5

[0083] Preparation of Compound Traditional Chinese Medicine Composition - Granules

[0084] (1) Weighing: Weigh 22 parts by weight of Antrodia camphorata, 12 parts by weight of Paeonia suffruticosa, 6 parts by weight of Cynanchum paniculatum, 6 parts by weight of Cicadae periostracum, 1.5 parts by weight of Calculus bovis, 0.6 parts by weight of Borneol and 6 parts by weight of Mentha haplocalyx.

[0085] (2) Enzymatic hydrolysis: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx were dried, pulverized and passed through a 100-mesh sieve, and mixed with purified water (material-liquid ratio of 1:8 g / mL). Xylanase was added and enzymatically hydrolyzed by sonication at 40℃, pH 4, 200W and 20kHz for 3 hours. The enzyme was inactivated at 80℃ for 20 minutes. β-glucosidase was added and enzymatically hydrolyzed by sonication at 40℃, pH 5, 200W and 20kHz for 60 minutes. The enzyme was inactivated at 80℃ for 20 minutes. Figinase was added and enzymatically hydrolyzed by sonication at 37℃, pH 7, 200W and 20kHz for 40 minutes. The enzyme was inactivated at 85℃ for 15 minutes. The mixture was filtered to obtain the enzymatic hydrolysate.

[0086] The amount of xylanase added is 0.3% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; the amount of β-glucosidase added is 2% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; and the amount of fig protease added is 0.2% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx.

[0087] (3) Fermentation: After adding glucose to the enzymatic hydrolysate, inoculate with compound microorganisms and anaerobic ferment at 35℃ and pH 6 for 72h, sterilize at 80℃ for 20min, centrifuge at 2500rpm for 20min, take the supernatant, concentrate under reduced pressure, spray dry to 3% water content to obtain fermented dry extract powder.

[0088] The amount of glucose added is preferably 1% of the mass of the enzymatic hydrolysate; the compound microorganism is composed of Bifidobacterium animalis subsp. lactis and Lactobacillus digestans in a weight ratio of 1:2, and the inoculation amount of the compound microorganism is 1%.

[0089] (4) Inclusion: β-cyclodextrin was added to purified water and stirred at 65°C until completely dissolved to obtain an aqueous solution of β-cyclodextrin. Borneol was dissolved in anhydrous ethanol to obtain an ethanol solution of borneol. The ethanol solution of borneol was slowly added dropwise to the aqueous solution of β-cyclodextrin (while stirring) to obtain a mixture. The mixture was magnetically stirred at 300 rpm for 2 h in a constant temperature water bath at 38°C, cooled to room temperature, stirred for another 1 h, and allowed to stand at 4°C for 12 h. The mixture was then filtered, the precipitate was collected, dried at 38°C to a water content of 4%, and pulverized through a 100-mesh sieve to obtain the borneol-β-CD inclusion complex. The concentration of β-cyclodextrin in the aqueous solution of β-cyclodextrin was 30 mg / mL, the concentration of borneol in the ethanol solution of borneol was 45 mg / mL, and the volume ratio of the aqueous solution of β-cyclodextrin to the ethanol solution of borneol was 10:1.

[0090] (5) Granule preparation: The bezoar is pulverized and passed through a 400-mesh sieve, and mixed with fermented dry extract powder, borneol-β-CD inclusion complex, lactose, microcrystalline cellulose, sodium carboxymethyl starch, and steviol glycosides to obtain a mixture. A 70% volume percentage ethanol solution is added, and the mixture is granulated and sized. Magnesium stearate is added and mixed to obtain granules. The weight ratio of bezoar, lactose, microcrystalline cellulose, sodium carboxymethyl starch, steviol glycosides, and magnesium stearate is 1:15:10:3:0.3:0.3. The amount of ethanol solution added is 15% of the mass of the mixture.

[0091] Example 6

[0092] Preparation of Compound Traditional Chinese Medicine Composition - Granules

[0093] (1) Weighing: Weigh 30 parts of Antrodia camphorata, 20 parts of Paeonia suffruticosa, 10 parts of Cynanchum paniculatum, 10 parts of Cicadae periostracum, 3 parts of Calculus bovis, 1 part of Borneol and 10 parts of Mentha haplocalyx.

[0094] (2) Enzymatic hydrolysis: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx were dried, pulverized and passed through a 200-mesh sieve, and then mixed with purified water (material-to-liquid ratio of 1:15 g / mL). Xylanase was added and the mixture was enzymatically hydrolyzed by sonication at 50℃, pH 6, 300W and 30kHz for 1 h. The enzyme was then inactivated at 90℃ for 10 min. β-glucosidase was added and the mixture was enzymatically hydrolyzed by sonication at 50℃, pH 6, 300W and 30kHz for 40 min. The enzyme was then inactivated at 90℃ for 10 min. Figinase was added and the mixture was enzymatically hydrolyzed by sonication at 40℃, pH 8, 300W and 30kHz for 40 min. The enzyme was then inactivated at 90℃ for 10 min. The mixture was filtered to obtain the enzymatic hydrolysate.

[0095] The amount of xylanase added is 0.8% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; the amount of β-glucosidase added is 5% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; and the amount of fig protease added is 0.5% of the total mass of the Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx.

[0096] (3) Fermentation: After adding glucose to the enzymatic hydrolysate, inoculate with compound microorganisms and anaerobic ferment at 40℃ and pH 7 for 24h, sterilize at 90℃ for 10min, centrifuge at 3500rpm for 10min, take the supernatant, concentrate under reduced pressure, and spray dry to 5% water content to obtain fermented dry extract powder.

[0097] The amount of glucose added is preferably 3% of the mass of the enzymatic hydrolysate; the compound microorganism is composed of Bifidobacterium animalis subsp. lactis and Lactobacillus digestans in a weight ratio of 3:5, and the inoculation amount of the compound microorganism is 3%.

[0098] (4) Inclusion: β-cyclodextrin was added to purified water and stirred at 70°C until completely dissolved to obtain an aqueous solution of β-cyclodextrin. Borneol was dissolved in anhydrous ethanol to obtain an ethanol solution of borneol. The ethanol solution of borneol was slowly added dropwise to the aqueous solution of β-cyclodextrin (while stirring) to obtain a mixture. The mixture was magnetically stirred at 430 rpm for 1 h in a constant temperature water bath at 42°C, cooled to room temperature, and stirred for another 1 h. The mixture was allowed to stand at 4°C for 12 h, filtered, and the precipitate was collected. The precipitate was dried at 42°C to a water content of 3%, pulverized and passed through a 100-mesh sieve to obtain the borneol-β-CD inclusion complex. The concentration of β-cyclodextrin in the aqueous solution of β-cyclodextrin was 32 mg / mL, the concentration of borneol in the ethanol solution of borneol was 48 mg / mL, and the volume ratio of the aqueous solution of β-cyclodextrin to the ethanol solution of borneol was 10:1.

[0099] (5) Granule preparation: The bezoar is pulverized and passed through a 600-mesh sieve, and mixed with fermented dry extract powder, borneol-β-CD inclusion complex, lactose, microcrystalline cellulose, sodium carboxymethyl starch, and steviol glycosides to obtain a mixture. A 75% (v / v) ethanol solution is added, and the mixture is granulated and sized. Magnesium stearate is added and mixed to obtain granules. The weight ratio of bezoar, lactose, microcrystalline cellulose, sodium carboxymethyl starch, steviol glycosides, and magnesium stearate is 3:25:20:6:0.8:0.8. The amount of ethanol solution added is 25% of the mass of the mixture.

[0100] Example 7

[0101] Preparation of Compound Traditional Chinese Medicine Composition - Cream

[0102] Steps (1)-(3) are the same as in Example 1;

[0103] (4) Preparation of ointment: Mix the traditional Chinese medicine powder, borneol-β-CD inclusion complex and bezoar (crushed and passed through a 500-mesh sieve) to obtain the traditional Chinese medicine composition; mix white petrolatum, octadecanol and glyceryl monostearate, melt in a water bath at 80°C to obtain the oil phase; mix glycerin, sodium dodecyl sulfate and water to obtain the aqueous phase; slowly add the oil phase; stir at 80°C and 1000 rpm for 10 min; cool to 40°C; mix with the traditional Chinese medicine composition; stir at 300 rpm for 60 min to obtain the ointment.

[0104] Example 8

[0105] Preparation of compound traditional Chinese medicine composition - gel

[0106] Steps (1)-(3) are the same as in Example 1;

[0107] (4) Preparation of gel: Mix the Chinese medicine powder, borneol-β-CD inclusion complex and bezoar (crushed and passed through a 500-mesh sieve) to obtain the Chinese medicine composition; add carbomer 940 to water to fully swell, add triethanolamine to adjust the pH value to 7, and it becomes a transparent gel. Mix it with the Chinese medicine composition and stir at 200 rpm for 60 min to obtain the gel.

[0108] The weight ratio of the traditional Chinese medicine composition, carbomer 940, triethanolamine and water is 10:3:2:85.

[0109] Comparative Example 1

[0110] spray

[0111] The specific implementation method is the same as that in Example 1, except that the ethanol solution with a volume percentage of 65% in step (2) is replaced with purified water.

[0112] Comparative Example 2

[0113] Granules

[0114] The specific implementation method is the same as that in Example 4, except that the enzymatic hydrolysis step (2) is as follows: Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum and Mentha haplocalyx are dried, pulverized and passed through a 150-mesh sieve, and then mixed with purified water (the material-to-liquid ratio is 1:10 g / mL). Pectinase is added, and the mixture is enzymatically hydrolyzed by sonication at 45°C, pH 5, 250W and 25kHz for 2 hours. The enzyme is then inactivated at 85°C for 15 minutes. Cellulase is added, and the mixture is enzymatically hydrolyzed by sonication at 45°C, pH 5.5, 250W and 25kHz for 50 minutes. The enzyme is then inactivated at 85°C for 15 minutes. Papain is added, and the mixture is enzymatically hydrolyzed by sonication at 60°C, pH 7, 250W and 25kHz for 35 minutes. The enzyme is then inactivated at 85°C for 10 minutes. The mixture is filtered to obtain the enzymatic hydrolysate.

[0115] Among them, pectinase was purchased from Jinan Jieyang Biotechnology Co., Ltd., product number JY222, with an enzyme activity of 100,000 U / g; cellulase was purchased from Hebei Pinke Biotechnology Co., Ltd., product number 0325-100g, with an enzyme activity of 5,000 U / g; and papain was purchased from Shandong Jinchengda Biotechnology Co., Ltd., product number M587-01, with an enzyme activity of 100,000 U / g. The amount of pectinase added was 0.5% of the total mass of the above-mentioned Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; the amount of cellulase added was 3% of the total mass of the above-mentioned Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx; and the amount of papain added was 0.4% of the total mass of the above-mentioned Antrodia camphorata, Paeonia suffruticosa, Cynanchum paniculatum, Cicadae periostracum, and Mentha haplocalyx.

[0116] The difference between this comparative example and Example 4 is that xylanase is replaced with pectinase, β-glucosidase is replaced with cellulase, and fig protease is replaced with papain.

[0117] Comparative Example 3

[0118] The specific implementation method is the same as in Example 4, except that the compound microorganisms in step (3) fermentation are composed of Bifidobacterium longum and Lactobacillus helveticus in a weight ratio of 2:4. Both Bifidobacterium longum and Lactobacillus helveticus were purchased from the China Industrial Microbial Culture Collection Center. Bifidobacterium longum CI CC 6207 had a cell activity of 3 billion CFU / g, and Lactobacillus helveticus CI CC 24940 had a cell activity of 1.5 billion CFU / g. The fermentation parameters remained unchanged.

[0119] Experimental Example 1

[0120] Animal experiments

[0121] 1. Grouping and Dosing

[0122] BALB / c mice aged 6-8 weeks were selected, with half males and half females, and were divided into 8 groups (blank group, model group, Example 1 group, Example 4 group, Example 1 + Example 4 group, Comparative Example 1 group, Comparative Example 2 group and Comparative Example 3 group), with 30 mice in each group. There were no significant differences between the mice in each group, and they were comparable.

[0123] Mice in all groups except the control group were used to establish an allergic rhinitis model.

[0124] Sensitization injection: On day 1, inject 0.2 mL of a mixture containing 100 g ovalbumin and 2 mg aluminum hydroxide into the peritoneum; repeat the intraperitoneal injection once on day 14, at the same dose as day 1.

[0125] Stimulation phase: Starting from day 21, administer 5% ovalbumin solution into the nasal cavity of mice once a day for 7 consecutive days using a micropipette, 10L per nostril (20L in total).

[0126] The control group mice were challenged by intraperitoneal injection and nasal drop of the same volume of physiological saline.

[0127] Behavioral observations were conducted on mice in each group to confirm that allergic rhinitis was successfully modeled in mice in all groups except the control group.

[0128] On day 28, mice in each group were administered the drug, and the administration regimens for each group were as follows:

[0129] Control group: No drug treatment was given.

[0130] Model group: No drug treatment was given.

[0131] Example 1 group: The compound Chinese medicine composition-spray prepared in Example 1 was used for nasal administration. The nasal spray was applied once a day, 10L per nostril each time (20L in total), starting from day 28 and continuing for 14 days.

[0132] Example 4 group: The compound traditional Chinese medicine composition-granules prepared in Example 4 were administered by gavage once a day at a dose of 0.2 g / kg for 14 consecutive days starting from day 28.

[0133] Example 1 + Example 4 group: Combined administration of the spray from Example 1 and the granules from Example 4: nasal spray, once daily, 10L per nostril (total 20L); gavage, once daily, at a dose of 0.2g / kg, starting from day 28 for 14 consecutive days. Administration time: starting from day 21 for 14 consecutive days.

[0134] Comparative Example 1: The compound Chinese medicine composition-spray prepared in Comparative Example 1 was administered nasally as a nasal spray once a day, 10L per nostril each time (20L in total), starting from day 28 for 14 consecutive days.

[0135] Comparative Example 2: The granules prepared in Comparative Example 2 were administered by gavage once daily at a dose of 0.2 g / kg for 14 consecutive days starting from day 28.

[0136] Comparative Example 3: The granules prepared in Comparative Example 3 were administered by gavage once daily at a dose of 0.2 g / kg for 14 consecutive days starting from day 28.

[0137] During the medication period, except for the control group, all other groups continued to use 5% ovalbumin solution for nasal stimulation daily, while the control group used the same volume of physiological saline for nasal stimulation. Nasal administration was performed 1 hour before nasal stimulation.

[0138] 2. Within 10 minutes after the last stimulation, observe and record the number of sneezes and nose scratches of mice in each group. The specific results are shown in Table 1.

[0139] Table 1. Number of sneezes and nose scratches in mice of each group

[0140] Group Number of sneezes Number of times to scratch nose Blank group 3.25 8.64 Model group 18.73 26.26 Example 1 7.36 15.43 Example 4 8.07 16.05 Example 1 + Example 4 5.35 12.84 Comparative Example 1 9.96 17.65 Comparative Example 2 9.82 17.28 Comparative Example 3 10.64 19.53

[0141] As shown in Table 1, compared with the control group, the number of sneezes and nose scratches in the model group mice was significantly increased, indicating successful modeling. The medication group significantly reduced the number of sneezes and nose scratches in mice compared to the model group. The combination of Examples 1 and 4 significantly reduced the number of sneezes and nose scratches in mice, showing the best effect in treating allergic rhinitis. A comparison of the data from Example 1 and Comparative Example 1 shows that ethanol extraction, compared with purified water extraction, is more effective in alleviating allergic rhinitis in mice. A comparison of the data from Example 2 and Comparative Examples 2-3 shows that different enzyme combinations and different microbial combinations in treating traditional Chinese medicine have varying degrees of impact on the efficacy of the granules.

[0142] 2. After observing and recording the number of sneezes and nose scratches of mice in each group, blood was collected from the orbital venous plexus under anesthesia to prepare serum. The levels of IgE and OVA-sIgE in the serum were detected by ELISA. The ELISA kit used was purchased from Shanghai Huzheng Biotechnology Co., Ltd., catalog number HS4859. The levels of IgE and OVA-sIgE in the serum of mice in each group are shown in Table 2.

[0143] Table 2. Serum IgE and OVA-sIgE levels in each group of mice

[0144] Group IgE (ng / mL) OVA-sIgE (ng / mL) Blank group 241.23 35.46 Model group 452.74 150.25 Example 1 314.92 62.46 Example 4 306.98 60.23 Example 1 + Example 4 285.75 48.51 Comparative Example 1 335.01 68.37 Comparative Example 2 325.48 65.08 Comparative Example 3 328.83 67.82

[0145] As shown in Table 2, compared with the blank group, the serum IgE and OVA-sIgE levels in the model group were significantly increased. The levels of IgE and OVA-sIgE in the medication groups decreased to varying degrees compared with the model group. The decrease in serum IgE and OVA-sIgE levels was most pronounced in the Example 1 + Example 4 groups. A comparison of the data from Example 1 and Comparative Example 1 shows that the effective components obtained from ethanol extraction are more effective in treating allergic rhinitis than those obtained from purified water extraction. A comparison of the data from Example 2 and Comparative Examples 2-3 shows that different enzyme combinations and different microbial combinations in the treatment of traditional Chinese medicine have varying degrees of impact on the efficacy of the granules, indicating that the various enzymes in the granule preparation process of this invention have a synergistic effect, and the compound microorganisms *Bifidobacterium animalis* subsp. *lactotrichum* and *Lactobacillus spp.* have a synergistic effect, which can improve the treatment effect of allergic rhinitis.

[0146] The data in Tables 1 and 2 show that the combined use of spray and granules has the best therapeutic effect on the model mice. Therefore, spray and granules were used in clinical trials to treat allergic rhinitis.

[0147] Experimental Example 2

[0148] clinical

[0149] 1. Case

[0150] Inclusion criteria: Individuals who have not received other drug treatments in the past 2 weeks; nasal itching, nasal congestion, paroxysmal sneezing and clear watery nasal discharge, with 4 or more symptom episodes per week, or 4 or more symptom episodes per year; positive allergen skin test or positive allergen-specific IgE antibody test; nasal examination reveals pale and edematous nasal mucosa, and watery secretions in the nasal passages; age 20-60 years; informed consent obtained.

[0151] Exclusion criteria: those who have received other drug treatments in the past 2 weeks; those with nasal symptoms caused by infectious diseases; pregnant or breastfeeding patients; and those with poor compliance and inability to cooperate.

[0152] Based on the inclusion and exclusion criteria, 150 patients with allergic rhinitis were selected and randomly divided into 3 groups. There were no significant differences in age, gender, and disease severity among the three groups (P>0.05), indicating that they were comparable.

[0153] 2. Treatment methods

[0154] Example group: Spray 1 in each nostril of Example 1, 3 times a day, and take 5g of granules of Example 4, 3 times a day, dissolved in warm water.

[0155] Comparative control group: Comparative control group 1 sprayed once in each nostril 3 times a day, and took 5g of granules from comparative control group 2 3 times a day, dissolved in warm water.

[0156] Positive group: Nasal spray (National Drug Approval Number Z33020423, 15 ml, Zhejiang Kang Enbei Pharmaceutical Co., Ltd.) 1 spray per nostril 3 times a day, and take Nasal Congestion Relief Granules (National Drug Approval Number Z20030071, 15 g × 10 sachets, Shandong New Era Pharmaceutical Co., Ltd.) 1 sachet each time, 3 times a day, dissolved in boiling water.

[0157] Each group received two treatment courses, each lasting seven days.

[0158] 3. Efficacy criteria

[0159] Cured: No more episodes of nasal itching, nasal congestion, paroxysmal sneezing, and runny nose with clear discharge;

[0160] Effective: The frequency of nasal itching, nasal congestion, paroxysmal sneezing, and runny nose decreased by more than 50% compared with before treatment;

[0161] Ineffective: No improvement or reduction of less than 50% in the frequency of nasal itching, nasal congestion, paroxysmal sneezing, and runny nose compared to before treatment.

[0162] Overall effective rate (%) = (cured cases + effective cases) ÷ 50 cases × 100%.

[0163] Table 3. Efficacy of the Example Group, Comparative Group, and Positive Group

[0164] Group cured cases Valid example Invalid example Overall effectiveness (%) Example group 33 14 3 94 Comparative group 24 20 6 88 positive group 18 27 5 90

[0165] As shown in Table 3, the embodiment group of the present invention can significantly increase the number of cured cases, and the total effective rate is also higher than that of the control group and the positive group.

[0166] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Use of a composite traditional Chinese medicine composition in the preparation of a medicament for treating allergic rhinitis, wherein the medicament is in the form of granules, and the composite traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Antrodia cinnamomea 20-30 parts, Radix Paeoniae 10-20 parts, Radix Polygalae 5-10 parts, Periostracum Cicadae 5-10 parts, ox gall 1-3 parts, borneol 0.5-1 part, and Mentha haplocalyx 5-10 parts; ​ The preparation method of the granules comprises the following steps: drying, crushing, and mixing Antrodia cinnamomea, Radix Paeoniae, Radix Polygalae, Periostracum Cicadae, and Mentha haplocalyx with water, sequentially adding xylanase, β-glucosidase, and ficin for ultrasonic enzymolysis, filtering to obtain an enzymolysis liquid, adding glucose, inoculating with complex microorganisms for anaerobic fermentation, filtering to obtain a fermentation liquid, reducing pressure concentration, spray drying to obtain fermented dry extract powder, dissolving borneol in anhydrous ethanol to obtain a borneol ethanol solution, slowly adding the borneol ethanol solution into a β-cyclodextrin water solution, stirring in a 35-45 ℃ water bath for 1-2 h, standing to precipitate, filtering, and drying the precipitate to obtain borneol-β-CD inclusion compound, and mixing, granulating ox gall powder, the fermented dry extract powder, the borneol-β-CD inclusion compound, a filler, a disintegrant, a lubricant, and a flavoring agent to obtain the granules. The complex microorganisms for fermentation are composed of Bifidobacterium animalis lactis and Lactobacillus alimentarius at a weight ratio of 1-3:2-5, the addition amount of the complex microorganisms is 0.8%-1.2% of the total mass of Antrodia cinnamomea, Radix Paeoniae, Radix Polygalae, Periostracum Cicadae, and Mentha haplocalyx, the fermentation temperature is 35-40 ℃, the pH value is 6-7, and the time is 24-72 h. The filler is selected from lactose or microcrystalline cellulose.

2. Use according to claim 1, characterized in that, The addition amount of the xylanase is 0.3%-0.8% of the total mass of Antrodia cinnamomea, Radix Paeoniae, Radix Polygalae, Periostracum Cicadae, and Mentha haplocalyx, the enzymolysis temperature is 40-50 ℃, the pH value is 4-6, the ultrasonic power is 200-300 W, the frequency is 20-30 kHz, and the time is 1-3 h; the addition amount of the β-glucosidase is 2%-5% of the total mass of Antrodia cinnamomea, Radix Paeoniae, Radix Polygalae, Periostracum Cicadae, and Mentha haplocalyx, the enzymolysis temperature is 40-50 ℃, the pH value is 5-6, the ultrasonic power is 200-300 W, the frequency is 20-30 kHz, and the time is 40-60 min; and the addition amount of the ficin is 0.2%-0.5% of the total mass of Antrodia cinnamomea, Radix Paeoniae, Radix Polygalae, Periostracum Cicadae, and Mentha haplocalyx, the enzymolysis temperature is 37-40 ℃, the pH value is 7-8, the ultrasonic power is 200-300 W, the frequency is 20-30 kHz, and the time is 30-40 min.

3. Use according to claim 1, characterized in that, The inclusion comprises the following steps: dissolving β-cyclodextrin in water to obtain a β-cyclodextrin water solution, dissolving borneol in anhydrous ethanol to obtain a borneol ethanol solution, slowly adding the borneol ethanol solution into the β-cyclodextrin water solution, stirring in a 35-45 ℃ water bath for 1-2 h, standing to precipitate, filtering, and drying the precipitate to obtain borneol-β-CD inclusion compound.