Compound traditional Chinese medicine composition, preparation method thereof and application of compound traditional Chinese medicine composition in preparation of medicine for treating allergic rhinitis

Abstract

The invention provides a compound traditional Chinese medicine composition, a preparation method thereof and application of the compound traditional Chinese medicine composition in preparation of medicine for treating allergic rhinitis, and belongs to the technical field of traditional Chinese medicine. The compound traditional Chinese medicine composition comprises antrodia camphorata, cortex moutan, paniculate swallowwort root, cicada slough, calculus bovis, borneol and mint. The monarch drug antrodia camphorata can fundamentally regulate immunity and resist inflammation and detumescence, the ministerial drugs cortex moutan, cynanchum paniculatum and cicada slough can assist in resisting allergy and dispelling wind and clearing heat, the adjuvant drugs calculus bovis and borneol can reduce phlegm, induce resuscitation and clear heat and relieve pain, and the envoy drug mint can guide the drugs upwards and relieve local symptoms. The traditional Chinese medicine is used for treating allergic rhinitis by adopting an oral administration and external application mode, plays a whole body regulating role and improves the immunity by oral administration, and is used for the nose to quickly relieve symptoms by external application. The traditional Chinese medicine composition treats both symptoms and root causes, all the medicine components are mutually compounded and synergized, the anti-inflammatory, anti-allergic and immunoregulation effects are enhanced, and the effect of treating allergic rhinitis is achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a compound traditional Chinese medicine composition, a preparation method thereof, and application of the compound traditional Chinese medicine composition in preparing a medicine for treating allergic rhinitis. Background Art

[0002] Allergic rhinitis (AR), also known as allergic rhinitis, is primarily an IgE-mediated, non-infectious inflammatory disease of the nasal mucosa. Clinically, it manifests with symptoms such as nasal itching, sneezing, nasal congestion, and watery nasal discharge. Allergic rhinitis not only impacts 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 sleep, learning, and work productivity. Currently, clinical treatments for allergic rhinitis primarily include medication, immunotherapy, and surgery.

[0003] Currently, medication is the mainstay of treatment for allergic rhinitis. Commonly used Western medications include antihistamines, glucocorticoids, and decongestants. While these medications can alleviate symptoms to a certain extent, they often carry side effects. For example, antihistamines may cause adverse reactions such as drowsiness and dry mouth, impacting patients' daily lives and work. Long-term use of glucocorticoids may lead to local or systemic adverse reactions, such as nasal dryness, epistaxis, and osteoporosis. Improper use of decongestants may cause drug-induced rhinitis and worsen the condition. Therefore, finding a safe, effective treatment with minimal side effects has become a major medical priority.

[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 and lack scientific experimental validation, and their efficacy and safety need to be further improved. Therefore, the development of a safe, effective, and minimally side-effected TCM composition for the treatment of allergic rhinitis has important clinical significance and social value. Summary of the Invention

[0005] The purpose of the present invention is to provide a composite Chinese medicine composition and a preparation method thereof and use thereof in preparing a drug for treating allergic rhinitis. Allergic rhinitis is treated by an oral + external application method. The oral administration exerts a systemic regulatory effect and improves immunity, while the external application acts on the nose, quickly relieves symptoms, and has a significant therapeutic effect.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The invention provides a compound traditional Chinese medicine composition for treating allergic rhinitis. The compound traditional Chinese medicine composition comprises the following raw materials in parts by weight: 20-30 parts of Antrodia cinnamomea, 10-20 parts of Cortex Moutan, 5-10 parts of Cynanchum chinense, 5-10 parts of Periostracum cicadae, 1-3 parts of Bezoar, 0.5-1 part of Borneolum Syntheticum, and 5-10 parts of Menthol.

[0008] The present invention also provides the use of the above-mentioned compound Chinese medicine composition in preparing medicine for treating allergic rhinitis.

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

[0010] More preferably, the preparation method of the spray comprises: drying and crushing Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and mint, adding ethanol solution, soaking in ultrasound, performing reflux extraction, filtering, concentrating under reduced pressure, and drying to obtain Chinese medicine powder; borneol is included in β-cyclodextrin, drying and crushing to obtain borneol-β-CD inclusion complex; crushing bezoar, mixing with 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 power of ultrasonic immersion is 200-300W, the frequency is 20-30kHz, and the time is 25-35min.

[0012] More preferably, the solid-liquid ratio of the reflux extraction is 1:8-10 g / mL, the temperature is 70-80° C., and the number of extractions is 1-3 times, each time for 40-60 min.

[0013] Preferably, the preparation method of the granules comprises: drying and crushing Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and mint, mixing them with water, adding xylanase, β-glucosidase and ficin in sequence for ultrasonic enzymolysis, filtering to obtain an enzymatic solution, adding glucose, inoculating composite microorganisms for anaerobic fermentation, filtering to obtain a fermentation liquid, concentrating under reduced pressure, spray drying to obtain a fermentation dry extract powder; borneol is included in β-cyclodextrin, dried and crushed to obtain a borneol-β-CD inclusion complex; crushing bezoar, mixing it with the fermentation 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 the xylanase added is 0.3%-0.8% of the total mass of the Antrodia cinnamomea, Cortex Moutan, Cynanchum indicum, Periostracum cicadae and mint, the enzymolysis temperature is 40-50°C, 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 the β-glucosidase added is 2%-5% of the total mass of the Antrodia cinnamomea, Cortex Moutan, Cynanchum indicum, Periostracum cicadae and mint, the enzymolysis temperature is 40- 50°C, pH value is 5-6, ultrasonic power is 200-300W, frequency is 20-30kHz, and time is 40-60min; the added amount of the ficin is 0.2%-0.5% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum chinense, cicada slough and mint, the enzymolysis temperature is 37-40°C, pH value is 7-8, ultrasonic power is 200-300W, frequency is 20-30kHz, and time is 30-40min.

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

[0016] More preferably, the fermented composite microorganism is composed of animal Bifidobacterium lactis subspecies and digestive-associated Lactobacillus in a weight ratio of 1-3:2-5, and the added amount of the composite microorganism is 0.8%-1.2% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum chinense, cicada slough and mint. The fermentation temperature is 35-40°C, 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] The present invention provides a compound Chinese medicine composition for treating allergic rhinitis, comprising: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum Cicadae, Bezoar, Borneol, and Mentha. Among them, the main drug Antrodia cinnamomea fundamentally regulates immunity and reduces inflammation and swelling, the auxiliary drugs Cortex Moutan, Cynanchum chinense, and Periostracum Cicadae assist in anti-allergy, dispelling wind and clearing heat, the adjuvant drugs Bezoar and Borneol resolve phlegm, open the mind, clear heat and relieve pain, and the mint leads the drug upward and relieves local symptoms. When treating allergic rhinitis, the compound Chinese medicine composition of the present invention adopts an oral + external application method. The oral administration exerts a systemic regulatory effect and improves immunity, while the external application directly acts on the local nasal area, which can quickly relieve the symptoms of allergic rhinitis. The whole prescription treats both the symptoms and the root cause. The various medicinal ingredients are compounded and synergistically, enhancing the anti-inflammatory, anti-allergic, and immunomodulatory effects, while simultaneously relieving symptoms such as nasal congestion, nasal itching, sneezing, and runny nose through different pathways. The compound Chinese medicine composition of the present invention is all natural Chinese medicine with few side effects and is suitable for long-term use. It is particularly suitable for patients who are intolerant to or prone to developing drug resistance to Western medicine. DETAILED DESCRIPTION

[0019] The invention provides a compound traditional Chinese medicine composition for treating allergic rhinitis. The compound traditional Chinese medicine composition comprises the following raw materials in parts by weight: 20-30 parts of Antrodia cinnamomea, 10-20 parts of Cortex Moutan, 5-10 parts of Cynanchum chinense, 5-10 parts of Periostracum cicadae, 1-3 parts of Bezoar, 0.5-1 part of Borneolum Syntheticum, and 5-10 parts of Menthol.

[0020] The present invention also provides the use of the above-mentioned compound Chinese medicine composition in preparing medicine for treating allergic rhinitis.

[0021] The relationship between monarch, minister, assistant and envoy of the compound Chinese medicine composition of the present invention is as follows:

[0022] King of medicine: Antrodia cinnamomea

[0023] Antrodia cinnamomea is the main herb in this prescription, known for its heat-clearing and detoxifying properties, anti-inflammatory and swelling-reducing properties, and immune-regulating effects. Modern research indicates that the triterpenes and polysaccharides in Antrodia cinnamomea can significantly inhibit the release of inflammatory mediators, alleviate nasal mucosal inflammation, and enhance immunity, fundamentally alleviating the symptoms of allergic rhinitis. As the main herb, Antrodia cinnamomea plays a leading role in the prescription, targeting the core pathogenesis of allergic rhinitis (lung, spleen, and kidney deficiency, and invasion by exogenous pathogens).

[0024] Assistant drugs: Cortex Moutan, Cynanchum chinense, Periostracum Cicadae

[0025] Paeonia lactiflora bark (Danpi moutan bark) has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis, and providing anti-allergic effects. Its active ingredient, paeonol, inhibits histamine release, reduces congestion and edema in the nasal mucosa, and alleviates symptoms such as nasal congestion and runny nose. As an adjuvant, Paeonia lactiflora bark complements Antrodia cinnamomea in enhancing its anti-inflammatory and anti-allergic effects.

[0026] Cynanchum chinense has anti-itching, anti-allergic, and heat-clearing and detoxifying properties. Its active ingredient, paeonol, inhibits the release of inflammatory mediators, alleviating nasal congestion and increased secretions. As an adjuvant, it can enhance the immune and anti-inflammatory effects of Antrodia cinnamomea, while also improving nasal symptoms such as nasal congestion, itching, and runny nose.

[0027] Cicada sloughs have the effects of dispelling wind and heat, promoting lung function and relieving sore throat, and providing anti-allergic effects. The active ingredients in cicada sloughs can inhibit mast cell degranulation and reduce the release of inflammatory mediators, thereby alleviating symptoms such as nasal itching and sneezing. As an adjuvant, cicada sloughs work synergistically with paeonol to enhance the therapeutic effects of the monarch drug.

[0028] Adjuvants: bezoar, borneol

[0029] Bezoar (Cow Gall) has the effects of clearing heat and detoxifying, resolving phlegm, and invigorating the mind. The bile acids in bezoar can inhibit inflammation, reducing swelling and increased secretions in the nasal mucosa. As an adjuvant, bezoar assists the principal and secondary herbs in treating the complications of allergic rhinitis (such as phlegm-dampness obstruction and nasal obstruction), while also enhancing the anti-inflammatory effects of the formula.

[0030] Borneol has the effects of invigorating the mind, clearing away heat, and alleviating pain. It can quickly penetrate the nasal mucosa, relieving symptoms such as nasal congestion and headaches. As an adjuvant, borneol assists the principal and secondary herbs in improving local symptoms while enhancing drug penetration and bioavailability.

[0031] Adjuvant: Mint

[0032] Peppermint dispels wind and heat, clears the head, and relieves itching. The menthol in peppermint stimulates vasoconstriction in the nasal mucosa, alleviating nasal congestion. It also has a cooling and antipruritic effect, alleviating itching and sneezing. As an adjuvant, peppermint guides the other medicinal ingredients directly to the affected area in the nose, harmonizing them and enhancing the overall efficacy of the prescription.

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

[0034] Treats both the symptoms and the root cause: The main drug Antrodia cinnamomea fundamentally regulates immunity, fights inflammation and reduces swelling; the auxiliary drugs Cortex Moutan, Cynanchum cyrtonema, and Periostracum Cicadae assist in anti-allergy, dispel wind and clear heat; the adjuvant drugs Bezoar and Borneol resolve phlegm and open the orifices, clear heat and relieve pain, and the mint guides the medicine upward and relieves local symptoms. The whole prescription treats both the symptoms and the root cause, which not only relieves symptoms but also regulates physical constitution; Synergistic enhancement: The various drug ingredients are compounded and enhanced with each other to enhance the anti-inflammatory, anti-allergic and immune-regulating effects, and at the same time relieve symptoms such as nasal congestion, nasal itching, sneezing, and runny nose through different pathways; High safety: The drugs in the prescription are all natural Chinese medicines with small side effects, suitable for long-term use, especially for patients who are intolerant to or prone to drug resistance to Western medicine.

[0035] The dosage form of the medicine of the present invention is preferably decoction, pill, powder, granule, capsule, tablet, oral liquid, ointment, syrup, spray, or gel.

[0036] The preparation method of the spray of the present invention preferably comprises: drying and crushing Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and mint, adding ethanol solution, soaking in ultrasound, performing reflux extraction, filtering, concentrating under reduced pressure and drying to obtain traditional Chinese medicine powder; enclosing borneol with β-cyclodextrin, drying and crushing to obtain borneol-β-CD inclusion complex; crushing bezoar, mixing 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 particle size of the crushed powder of the present invention is preferably 100-200 mesh, more preferably 150 mesh. The crushing of the Chinese medicine of the present invention can increase the surface area, improve the extraction efficiency, destroy the cell structure, facilitate the dissolution of the components, make the extraction more uniform, save the extraction solvent and time, and facilitate the subsequent extraction effect.

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

[0039] The material-liquid ratio of the reflux extraction of the present invention is preferably 1:8-10 g / mL, more preferably 1:9 g / mL, the temperature is preferably 70-80°C, more preferably 75°C, the number of extractions is preferably 1-3 times, more preferably 2 times, and each time is preferably 40-60 minutes, more preferably 50 minutes. This step can destroy the cell structure, breaking the cell's constraints, allowing the active ingredients to be fully dissolved. Ethanol molecules can penetrate into the interior of the medicinal material more quickly and fully contact with the active ingredients, greatly increasing the dissolution rate of the active ingredients and increasing the solubility of the active ingredients in ethanol, shortening the extraction time, improving the extraction efficiency, and improving the purity and quality of the extract.

[0040] The solvent of the present invention is preferably ethanol and 1,2-propylene glycol, the isotonicity adjusting agent 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 mass ratio of the traditional Chinese medicine powder, solvent, isotonicity adjusting agent, thickener, preservative, antioxidant, and water is preferably 1-3:15-25:0.9:0.1-0.3:0.01-0.03:60-85, and more preferably 2:20:0.9:0.2:0.02:76.88.

[0041] The method of using the spray of the present invention is as follows: blow out nasal secretions to keep the nasal cavity unobstructed, shake the liquid medicine evenly, keep the head upright or slightly tilted forward, 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 and gently inhale to evenly distribute the liquid medicine on the nasal mucosa, 1-2 sprays per nostril, 3 times a day.

[0042] The externally applicable dosage forms of the present invention are ointment, spray and gel, all of which have the same active ingredients, namely, Chinese medicine composition (Chinese medicine powder, borneol-β-CD inclusion compound and bezoar), and the auxiliary materials vary according to the different dosage forms.

[0043] The ointment of the present invention is preferably an ointment, and the preparation method of the ointment preferably includes: mixing white vaseline, stearyl alcohol, 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 preparation method of the gel of the present invention preferably comprises: adding carbomer 940 into water to fully swell, adding triethanolamine to adjust the pH value to 7, forming a transparent gel, and mixing with the traditional Chinese medicine composition to obtain the gel.

[0045] The preparation method of the granules of the present invention preferably comprises: drying and crushing Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Menthol, mixing the mixture with water, sequentially adding xylanase, β-glucosidase and ficin for ultrasonic enzymolysis, filtering to obtain an enzymatic hydrolyzate, adding glucose, inoculating composite microorganisms for anaerobic fermentation, filtering to obtain a fermentation liquid, concentrating under reduced pressure, spray drying to obtain a fermentation dry extract powder; encapsulating borneol with β-cyclodextrin, drying and crushing to obtain a borneol-β-CD inclusion complex; crushing bezoar, mixing the crushed bezoar with the fermentation dry extract powder, the borneol-β-CD inclusion complex, a filler, a disintegrant, a lubricant and a flavoring agent, and granulating to obtain the granules.

[0046] The xylanase of the present invention was purchased from Jiangsu Maiden Biotechnology Co., Ltd. with the item number 02144 and an enzyme activity of 100,000 U / g; the β-glucosidase was purchased from Xi'an Zebang Biotechnology Co., Ltd. with the item number zb-6415 and an enzyme activity of 5000 U / g; and the fig proteinase was purchased from Jiangsu Huace Biotechnology Co., Ltd. with the item number 0 and an enzyme activity of 100,000 U / g. The amount of xylanase added according to the present invention is preferably 0.3%-0.8% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum chinense, cicada slough and mint, more preferably 0.5%, the enzymolysis temperature is preferably 40-50°C, more preferably 45°C, the pH value is preferably 4-6, more preferably 5, the ultrasonic power is preferably 200-300W, more preferably 250W, the frequency is preferably 20-30kHz, more preferably 25kHz, and the time is preferably 1-3h, more preferably 2h; the amount of β-glucosidase added is preferably 2%-5% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum chinense, cicada slough and mint, more preferably 3%, the enzymolysis temperature is preferably 40-50°C, more preferably 45°C, the pH value is preferably 5-6, more preferably The ultrasonic power is preferably 200-300W, more preferably 250W, the frequency is preferably 20-30kHz, more preferably 25kHz, and the time is preferably 40-60min, more preferably 50min; the addition amount of the ficin is preferably 0.2%-0.5% of the total mass of the Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha, more preferably 0.4%, the enzymolysis temperature is preferably 37-40°C, more preferably 38°C, the pH value is preferably 7-8, more preferably 7.5, the ultrasonic power is preferably 200-300W, more preferably 250W, the frequency is preferably 20-30kHz, more preferably 25kHz, and the time is preferably 30-40min, more preferably 35min. The cavitation effect, mechanical vibration effect, etc. of the ultrasonic wave in this step can accelerate the contact of the enzyme molecule with the substrate (medicinal material component), enhance the activity of the enzyme, and improve the rate of the enzymolysis reaction. At the same time, 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 complete and efficient.

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

[0048] The fermented composite microorganisms of the present invention are preferably composed of Bifidobacterium animalis subsp. lactis and Lactobacillus alimentarius in a weight ratio of 1-3:2-5, and the weight ratio is more preferably 2:4. Both Bifidobacterium animalis subsp. lactis and Lactobacillus alimentarius were purchased from the China Industrial Microbiological Culture Collection Center. The Bifidobacterium animalis subsp. lactis is Bifidobacterium animalis subsp. lactis CI CC21712 with a bacterial activity of 3 billion cfu / g, and the Lactobacillus alimentarius is Companilactobacillus alimentarius CICC 6284 with a bacterial activity of 1.5 billion cfu / g. The addition amount of the composite microorganism is preferably 0.8%-1.2% of the total mass of the Antrodia cinnamomea, Cortex Moutan, Cynanchum Root, Periostracum Cicadae and Mint, more preferably 1%, the addition amount of the glucose is preferably 1%-3% of the mass of the enzymatic hydrolyzate, more preferably 2%, the fermentation temperature is preferably 35-40°C, more preferably 37°C, the pH value is preferably 6-7, more preferably 6.5, and the time is preferably 24-72h, more preferably 36h. There is a synergistic effect between the animal Bifidobacterium lactis subspecies and the digestive-associated lactobacillus, and the combination of the two can improve the extraction rate and bioavailability of the effective ingredients in the fermentation of Antrodia cinnamomea, Cortex Moutan, Cynanchum Root, Periostracum Cicadae and Mint, and transform and modify the traditional Chinese medicine ingredients to improve the efficacy of treating allergic rhinitis.

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

[0050] The method of using the granules of the present invention is as follows: an adult takes 5 g each time, 3 times a day, with warm water.

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

[0052] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0053] In the following examples, unless otherwise specified, all methods are conventional.

[0054] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0055] Example 1

[0056] Preparation of compound Chinese medicine composition-spray

[0057] (1) Weighing: Weigh 25 parts by weight of Antrodia cinnamomea, 15 parts by weight of Cortex Moutan, 8 parts by weight of Cynanchum chinense, 8 parts by weight of Periostracum cicadae, 2 parts by weight of Bezoar, 0.8 parts by weight of Borneolum Syntheticum, and 8 parts by weight of Menthol;

[0058] (2) Ethanol extraction: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha were dried and ground respectively, and then mixed. A 65% ethanol solution was added at a solid-liquid ratio of 1:9 g / mL. The mixture was ultrasonically soaked at 250W and 25kHz for 30 minutes to obtain an ultrasonic mixture. The mixture was transferred to a reflux extraction device and refluxed at 75°C for 50 minutes 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 a Chinese medicine powder.

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

[0060] (4) Preparation of spray: After fully swelling, hydroxypropyl methylcellulose was mixed with purified water, and then mixed with Chinese medicine powder, borneol-β-CD inclusion compound, bezoar (grinded and passed through a 500-mesh sieve), anhydrous ethanol, 1,2-propylene glycol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water, and stirred at 300 rpm for 60 min to obtain a spray; wherein the weight ratio of Chinese medicine powder, anhydrous ethanol, 1,2-propylene glycol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water (total amount) was 2:12:8:0.9:0.2:0.02:76.88.

[0061] Example 2

[0062] Preparation of compound Chinese medicine composition-spray

[0063] (1) Weighing: Weigh 20 parts by weight of Antrodia cinnamomea, 10 parts by weight of Cortex Moutan, 5 parts by weight of Cynanchum chinense, 5 parts by weight of Periostracum cicadae, 1 part by weight of Bezoar, 0.5 parts by weight of Borneol, and 5 parts by weight of Menthol respectively;

[0064] (2) Ethanol extraction: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae, and Mentha were dried and ground separately, passed through a 100-mesh sieve, and then mixed. A 60% ethanol solution was added at a solid-liquid ratio of 1:8 g / mL. The mixture was ultrasonically soaked at 200 W and 20 kHz for 35 min to obtain an ultrasonic mixture. The mixture was transferred to a reflux extraction apparatus and refluxed at 80°C for 60 min. The mixture was filtered, and the filtrate was concentrated under reduced pressure and spray-dried to a water content of 4% to obtain a Chinese medicine powder.

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

[0066] (4) Preparation of spray: After fully swelling, hydroxypropyl methylcellulose was mixed with purified water, and then mixed with Chinese medicine powder, borneol-β-CD inclusion compound, bezoar (grinded and passed through a 400-mesh sieve), anhydrous ethanol, 1,2-propylene glycol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water, and stirred at 250 rpm for 90 min to obtain a spray; wherein the weight ratio of Chinese medicine powder, anhydrous ethanol, 1,2-propylene glycol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water (total amount) was 1:10:5:0.9:0.1:0.01:82.99.

[0067] Example 3

[0068] Preparation of compound Chinese medicine composition-spray

[0069] (1) Weighing: Weigh 30 parts by weight of Antrodia cinnamomea, 20 parts by weight of Cortex Moutan, 10 parts by weight of Cynanchum chinense, 10 parts by weight of Periostracum cicadae, 3 parts by weight of Bezoar, 1 part by weight of Borneolum Syntheticum, and 10 parts by weight of Menthol;

[0070] (2) Ethanol extraction: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha were dried and ground respectively, and then mixed. A 70% ethanol solution was added at a solid-liquid ratio of 1:10 g / mL. The mixture was ultrasonically soaked at 300W and 30kHz for 25 minutes to obtain an ultrasonic mixture. The mixture was transferred to a reflux extraction device and refluxed at 70°C for 3 times, each time for 40 minutes. The mixture was filtered, the filtrates were combined, concentrated under reduced pressure, and spray-dried to a water content of 2% to obtain a Chinese medicine powder.

[0071] (3) Inclusion: β-cyclodextrin was added to purified water and stirred at 70°C until completely dissolved to obtain a β-cyclodextrin aqueous solution; borneol was dissolved in anhydrous ethanol to obtain a borneol ethanol solution; the borneol ethanol solution was slowly added dropwise to the β-cyclodextrin aqueous solution (stirring while adding dropwise) to obtain a mixed solution; the mixture was stirred at 430 rpm in a constant temperature water bath at 42°C for 1 hour, cooled to room temperature, continued to stir for 1 hour, and allowed to stand at 4°C for 12 hours. The precipitate was filtered and collected, dried at 42°C to a moisture content of 3%, and crushed through a 100-mesh sieve to obtain a borneol-β-CD inclusion complex; wherein 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) Preparation of spray: After fully swelling, hydroxypropyl methylcellulose was mixed with purified water, and then mixed with Chinese herbal medicine powder, borneol-β-CD inclusion compound, bezoar (grinded and passed through a 600-mesh sieve), anhydrous ethanol, 1,2-propylene glycol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water, and stirred at 350 rpm for 50 min to obtain a spray; wherein the weight ratio of Chinese herbal medicine powder, anhydrous ethanol, 1,2-propylene glycol, sodium chloride, hydroxypropyl methylcellulose, benzalkonium chloride, EDTA-2Na and purified water (total amount) was 3:15:10:0.9:0.3:0.03:70.77.

[0073] Example 4

[0074] Preparation of compound Chinese medicine granules

[0075] (1) Weighing: Weigh 28 parts by weight of Antrodia cinnamomea, 18 parts by weight of Cortex Moutan, 7 parts by weight of Cynanchum chinense, 7 parts by weight of Periostracum cicadae, 2 parts by weight of Bezoar, 0.7 parts by weight of Borneolum Syntheticum, and 7 parts by weight of Menthol;

[0076] (2) Enzymolysis: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha were dried and crushed respectively, and then mixed with purified water (solid-liquid ratio was 1:10 g / mL). Xylanase was added, and ultrasonic enzymolysis was performed at 45°C, pH 5, 250W, and 25kHz for 2 hours, and the enzyme was inactivated at 85°C for 15 minutes. β-glucosidase was added, and ultrasonic enzymolysis was performed at 45°C, pH 5.5, 250W, and 25kHz for 50 minutes, and the enzyme was inactivated at 85°C for 15 minutes. Ficin was added, and ultrasonic enzymolysis was performed at 38°C, pH 7.5, 250W, and 25kHz for 35 minutes, and the enzyme was inactivated at 85°C for 10 minutes. The hydrolyzate was filtered to obtain the hydrolyzate.

[0077] Among them, the added amount of xylanase is 0.5% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, the added amount of β-glucosidase is 3% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, and the added amount of ficin is 0.4% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint.

[0078] (3) Fermentation: After adding glucose to the enzymatic hydrolysate, the composite microorganisms were inoculated and anaerobically fermented at 37°C and pH 6.5 for 36 hours, sterilized at 85°C for 15 minutes, and centrifuged at 3000 rpm for 15 minutes. The supernatant was collected, concentrated under reduced pressure, and spray-dried to a moisture content of 4% to obtain a fermented dry extract powder;

[0079] The amount of glucose added is 2% of the mass of the enzymatic hydrolyzate; the composite microorganism is composed of Bifidobacterium animalis subspecies lactis and Lactobacillus digesta in a weight ratio of 2:4, and the inoculation amount of the composite microorganism is 1%;

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

[0081] (5) Preparation of granules: bezoar is crushed and passed through a 500-mesh sieve, and mixed with fermentation dry extract powder, borneol-β-CD inclusion compound, lactose, microcrystalline cellulose, sodium carboxymethyl starch, and steviol glycoside to obtain a mixture, and an ethanol solution with a volume percentage of 70% is added, granulated and sized, and magnesium stearate is added and mixed to obtain granules; the weight ratio of the bezoar, lactose, microcrystalline cellulose, sodium carboxymethyl starch, steviol glycoside, and magnesium stearate is 2:20:15:5:0.5:0.5; the amount of the ethanol solution added is 18% of the mass of the mixture.

[0082] Example 5

[0083] Preparation of compound Chinese medicine granules

[0084] (1) Weighing: Weigh 22 parts by weight of Antrodia cinnamomea, 12 parts by weight of Cortex Moutan, 6 parts by weight of Cynanchum chinense, 6 parts by weight of Periostracum cicadae, 1.5 parts by weight of Bezoar, 0.6 parts by weight of Borneol, and 6 parts by weight of Menthol respectively;

[0085] (2) Enzymolysis: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha were dried and crushed respectively, passed through a 100-mesh sieve, and then mixed with purified water (solid-liquid ratio of 1:8 g / mL). Xylanase was added, and ultrasonic enzymolysis was performed at 40°C, pH 4, 200W, and 20kHz for 3 hours, and the enzyme was inactivated at 80°C for 20 minutes. β-glucosidase was added, and ultrasonic enzymolysis was performed at 40°C, pH 5, 200W, and 20kHz for 60 minutes, and the enzyme was inactivated at 80°C for 20 minutes. Ficin was added, and ultrasonic enzymolysis was performed at 37°C, pH 7, 200W, and 20kHz for 40 minutes, and the enzyme was inactivated at 85°C for 15 minutes. The hydrolyzate was filtered to obtain the hydrolyzate.

[0086] Among them, the added amount of xylanase is 0.3% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, the added amount of β-glucosidase is 2% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, and the added amount of ficin is 0.2% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint.

[0087] (3) Fermentation: After adding glucose to the enzymatic hydrolysate, the composite microorganisms were inoculated and anaerobically fermented at 35°C and pH 6 for 72 hours, sterilized at 80°C for 20 minutes, and centrifuged at 2500 rpm for 20 minutes. The supernatant was collected, concentrated under reduced pressure, and spray-dried to a moisture content of 3% to obtain a fermented dry extract powder;

[0088] The added amount of glucose is preferably 1% of the mass of the enzymatic hydrolyzate; the composite microorganism is composed of Bifidobacterium animalis subspecies lactis and Lactobacillus digesta in a weight ratio of 1:2, and the inoculation amount of the composite microorganism is 1%;

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

[0090] (5) Preparation of granules: bezoar is crushed and passed through a 400-mesh sieve, and mixed with fermentation dry extract powder, borneol-β-CD inclusion compound, lactose, microcrystalline cellulose, sodium carboxymethyl starch, and steviol glycoside to obtain a mixture, and an ethanol solution with a volume percentage of 70% is added, granulated and sized, and magnesium stearate is added and mixed to obtain granules; the weight ratio of the bezoar, lactose, microcrystalline cellulose, sodium carboxymethyl starch, steviol glycoside, and magnesium stearate is 1:15:10:3:0.3:0.3; the amount of the ethanol solution added is 15% of the mass of the mixture.

[0091] Example 6

[0092] Preparation of compound Chinese medicine granules

[0093] (1) Weighing: Weigh 30 parts by weight of Antrodia cinnamomea, 20 parts by weight of Cortex Moutan, 10 parts by weight of Cynanchum chinense, 10 parts by weight of Periostracum cicadae, 3 parts by weight of Bezoar, 1 part by weight of Borneolum Syntheticum, and 10 parts by weight of Menthol;

[0094] (2) Enzymatic hydrolysis: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha were dried and crushed respectively, passed through a 200-mesh sieve, and then mixed with purified water (solid-liquid ratio of 1:15 g / mL). Xylanase was added, and ultrasonic enzymolysis was performed at 50°C, pH 6, 300W, and 30kHz for 1 hour, and the enzyme was inactivated at 90°C for 10 minutes. β-glucosidase was added, and ultrasonic enzymolysis was performed at 50°C, pH 6, 300W, and 30kHz for 40 minutes, and the enzyme was inactivated at 90°C for 10 minutes. Ficin was added, and ultrasonic enzymolysis was performed at 40°C, pH 8, 300W, and 30kHz for 40 minutes, and the enzyme was inactivated at 90°C for 10 minutes. The hydrolyzate was filtered to obtain the hydrolyzate.

[0095] Among them, the added amount of xylanase is 0.8% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, the added amount of β-glucosidase is 5% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, and the added amount of ficin is 0.5% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint.

[0096] (3) Fermentation: After adding glucose to the enzymatic hydrolysate, the composite microorganisms were inoculated and anaerobically fermented at 40°C and pH 7 for 24 hours, sterilized at 90°C for 10 minutes, and centrifuged at 3500 rpm for 10 minutes. The supernatant was collected, concentrated under reduced pressure, and spray-dried to a moisture content of 5% to obtain a fermented dry extract powder;

[0097] The added amount of glucose is preferably 3% of the mass of the enzymatic hydrolyzate; the composite microorganism is composed of Bifidobacterium animalis subspecies lactis and Lactobacillus digesta in a weight ratio of 3:5, and the inoculation amount of the composite microorganism is 3%;

[0098] (4) Inclusion: β-cyclodextrin was added to purified water and stirred at 70°C until completely dissolved to obtain a β-cyclodextrin aqueous solution; borneol was dissolved in anhydrous ethanol to obtain a borneol ethanol solution; the borneol ethanol solution was slowly added dropwise to the β-cyclodextrin aqueous solution (stirring while adding dropwise) to obtain a mixed solution; the mixture was stirred at 430 rpm in a constant temperature water bath at 42°C for 1 hour, cooled to room temperature, continued to stir for 1 hour, and allowed to stand at 4°C for 12 hours. The precipitate was filtered and collected, dried at 42°C to a water content of 3%, and crushed through a 100-mesh sieve to obtain a borneol-β-CD inclusion complex; wherein 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;

[0099] (5) Preparation of granules: bezoar is crushed and passed through a 600-mesh sieve, and mixed with fermentation dry extract powder, borneol-β-CD inclusion compound, lactose, microcrystalline cellulose, sodium carboxymethyl starch, and steviol glycoside to obtain a mixture, and an ethanol solution with a volume percentage of 75% is added, granulated and sized, and magnesium stearate is added and mixed to obtain granules; the weight ratio of the bezoar, lactose, microcrystalline cellulose, sodium carboxymethyl starch, steviol glycoside, and magnesium stearate is 3:25:20:6:0.8:0.8; the amount of the ethanol solution added is 25% of the mass of the mixture.

[0100] Example 7

[0101] Preparation of compound Chinese medicine composition-cream

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

[0103] (4) Preparation of cream: Chinese medicine powder, borneol-β-CD inclusion compound and bezoar (grinded and passed through a 500-mesh sieve) were mixed to obtain a Chinese medicine composition; white vaseline, octadecyl alcohol and glyceryl monostearate were mixed and melted in a water bath at 80°C to obtain an oil phase; glycerol, sodium lauryl sulfate and water were mixed to obtain an aqueous phase; the oil phase was slowly added and stirred at 80°C and 1000 rpm for 10 min. After cooling to 40°C, the mixture was mixed with the Chinese medicine composition and stirred at 300 rpm for 60 min to obtain a cream.

[0104] Example 8

[0105] Preparation of compound Chinese medicine composition-gel

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

[0107] (4) Preparation of gel: Traditional Chinese medicine powder, borneol-β-CD inclusion compound and bezoar (grinded and passed through a 500-mesh sieve) were mixed to obtain a traditional Chinese medicine composition; Carbomer 940 was added to water to fully swell, and triethanolamine was added to adjust the pH value to 7 to form a transparent gel. The mixture was mixed with the traditional Chinese medicine composition and stirred at 200 rpm for 60 min to obtain a gel;

[0108] Among them, 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 is the same as that of Example 1, except that the 65% by volume ethanol solution in step (2) is replaced by purified water.

[0112] Comparative Example 2

[0113] Granules

[0114] The specific implementation is the same as that of Example 4, except that the enzymatic hydrolysis step (2) is as follows: Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Mentha are dried and crushed through a 150-mesh sieve respectively, and then mixed with purified water (solid-liquid ratio is 1:10 g / mL), pectinase is added, ultrasonic enzymolysis is carried out at 45°C, pH 5, 250W, 25kHz for 2h, and the enzyme is inactivated at 85°C for 15min, cellulase is added, ultrasonic enzymolysis is carried out at 45°C, pH 5.5, 250W, 25kHz for 50min, and the enzyme is inactivated at 85°C for 15min, papain is added, ultrasonic enzymolysis is carried out at 60°C, pH 7, 250W, 25kHz for 35min, and the enzyme is inactivated at 85°C for 10min, and the hydrolyzate is obtained by filtration;

[0115] Among them, pectinase was purchased from Jinan Jieyang Biotechnology Co., Ltd., item number JY222, with an enzyme activity of 100,000 U / g, cellulase was purchased from Hebei Pinken Biotechnology Co., Ltd., item number 0325-100g, with an enzyme activity of 5000 U / g, and papain was purchased from Shandong Jinchengda Biotechnology Co., Ltd., item 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 Antrodia cinnamomea, Cortex Moutan, Cynanchum dahurica, Periostracum Cicadae and mint, the amount of cellulase added was 3% of the total mass of the Antrodia cinnamomea, Cortex Moutan, Cynanchum dahurica, Periostracum Cicadae and mint, and the amount of papain added was 0.4% of the total mass of the Antrodia cinnamomea, Cortex Moutan, Cynanchum dahurica, Periostracum Cicadae and mint.

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

[0117] Comparative Example 3

[0118] The specific implementation method is the same as that of Example 4, except that the composite microorganism fermented in step (3) is composed of Bifidobacterium longum and Lactobacillus helveticus in a weight ratio of 2:4. Bifidobacterium longum and Lactobacillus helveticus are purchased from the China Industrial Microorganism Culture Collection Center. Bifidobacterium longum CI CC 6207 has a bacterial activity of 3 billion cfu / g, and Lactobacillus helveticus CI CC 24940 has a bacterial activity of 1.5 billion cfu / g. The fermentation parameters remain unchanged.

[0119] Test Example 1

[0120] Animal experiments

[0121] 1. Grouping and Dosing

[0122] BALB / c mice aged 6-8 weeks were selected, half male and half female, and divided equally 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 was no significant difference in mice among the groups, and the mice were comparable.

[0123] Allergic rhinitis models were established in mice in other groups except the blank group.

[0124] Sensitization injection: On the first day, intraperitoneal injection of 0.2 mL of a mixture containing 100 g ovalbumin and 2 mg aluminum hydroxide was performed; on the 14th day, the intraperitoneal injection was repeated with the same dose as on the first day.

[0125] Challenge phase: starting from the 21st day, once a day for 7 consecutive days, a 5% ovalbumin solution was dripped into the nasal cavity of the mouse using a micropipette, 10 L per nostril (20 L in total).

[0126] The mice in the blank group were challenged with the same volume of normal saline by intraperitoneal injection and nasal drops.

[0127] Behavioral observations were performed on mice in each group to confirm that allergic rhinitis models were successfully established in mice in other groups except the blank group.

[0128] On the 28th day, each group of mice was administrated with the following medication regimen:

[0129] Blank group: no drug treatment.

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

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

[0132] Group 4 of Example: The compound Chinese medicine composition-granules prepared in Example 4 were administered orally once a day at a dose of 0.2 g / kg, starting from the 28th day and for 14 consecutive days.

[0133] Group Example 1 + Example 4: The spray of Example 1 and the granules of Example 4 were co-administered: nasal spray, once daily, 10 L per nostril (20 L total); oral administration, once daily, at a dose of 0.2 g / kg, starting on day 28 for 14 consecutive days. Administration duration: starting on day 21 for 14 consecutive days.

[0134] Comparative Example 1 group: The composite Chinese medicine composition-spray prepared in Comparative Example 1 was used for nasal administration, nasal spray, once a day, 10 L per nostril each time (20 L in total), starting from the 28th day, for 14 consecutive days.

[0135] Comparative Example 2 group: The granules prepared in Comparative Example 2 were administered orally once a day at a dose of 0.2 g / kg, starting from the 28th day and for 14 consecutive days.

[0136] Comparative Example 3 group: The granules prepared in Comparative Example 3 were administered orally once a day at a dose of 0.2 g / kg, starting from the 28th day and for 14 consecutive days.

[0137] During the treatment period, the other groups continued to be challenged with 5% ovalbumin solution by weight volume every day, and the blank group was challenged with the same volume of normal saline by weight volume. Nasal administration was performed 1 hour before the challenge.

[0138] 2. Within 10 minutes after the last challenge, the number of sneezing and nose scratching of mice in each group was observed and recorded. The specific results are shown in Table 1.

[0139] Table 1 The number of sneezing and nose scratching in mice in each group

[0140] Group Number of sneezes Number of nose scratching 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 the data of Table 1, relative to the blank group, the sneezing and scratching nose frequency of the model group mice significantly increased, indicating that the modeling was successful. The medication group can significantly reduce the sneezing and scratching nose frequency of mice relative to the model group. The embodiment 1+ embodiment 4 group can significantly reduce the sneezing and scratching nose frequency of mice, and has the best effect in treating allergic rhinitis. As shown in the data comparison of embodiment 1 and comparative example 1, the ethanol solution extraction can more alleviate the allergic rhinitis of mice relative to the purified water extraction. As shown in the data comparison of embodiment 2 and comparative example 2-3, different enzymes are coordinated and different microorganisms are combined to process Chinese medicine, and the drug effect of granules is had to varying degrees.

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

[0143] Table 2 The levels of IgE and OVA-sIgE in the serum of mice in each group

[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, the content of IgE and OVA-sIgE in the serum of the model group increased significantly relative to the blank group. The content of IgE and OVA-sIgE in the medication group decreased to varying degrees relative to the content of IgE and OVA-sIgE in the serum of the model group. The degree of decrease in the content of IgE and OVA-sIgE in the serum of Example 1+Example 4 groups was the most obvious. As shown in the data comparison of Example 1 and Comparative Example 1, the effective ingredient obtained by ethanol solution extraction relative to purified water extraction is more effective in treating allergic rhinitis. As shown in the data comparison of Example 2 and Comparative Examples 2-3, different enzymes and different microorganisms are combined to treat Chinese medicine, which has different degrees of influence on the efficacy of the granules, indicating that there is a synergistic effect between various enzymes in the preparation process of the granules of the present invention, and there is a synergistic effect between the composite microorganism Bifidobacterium animalis subspecies lactis and the digestive associated lactobacillus, which can improve the effect of treating allergic rhinitis.

[0146] From the data in Tables 1 and 2, it can be seen that the spray and granules acted together to achieve the best therapeutic effect on model mice. Therefore, the spray and granules were used to treat allergic rhinitis in clinical trials.

[0147] Test Example 2

[0148] clinical

[0149] 1. Case

[0150] Inclusion criteria: patients who had not received other medications in the past two weeks; had nasal itching, nasal congestion, paroxysmal sneezing, and watery runny nose, with symptoms occurring four or more times per week, or four or more weeks per year; had a positive allergen skin test or a positive allergen-specific IgE antibody test; had pale and edematous nasal mucosa and watery secretions in the nasal passages on nasal examination; were aged 20-60 years; and provided informed consent.

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

[0152] According to the inclusion and exclusion criteria, 150 patients with allergic rhinitis were selected and divided into three groups on average. There was no significant difference in age, gender, and condition among the three groups (P>0.05), indicating that the three groups were comparable.

[0153] 2. Treatment methods

[0154] Example group: spray Example 1 into each nostril once, 3 times a day, and take the granules of Example 4, 5 g each time, 3 times a day, with warm water.

[0155] Comparative Example Group: spray the spray of Comparative Example 1 into each nostril once, 3 times a day, and take the granules of Comparative Example 2, 5 g each time, 3 times a day, with warm water.

[0156] Positive group: 1 spray of Ditong Biyan Water (National Medicine Standard No. Z33020423, 15 ml, Zhejiang Kangenbei Pharmaceutical Co., Ltd.) in each nostril, 3 times a day, and take Biyuan Tongqiao Granules (National Medicine Standard No. Z20030071, 15 g × 10 bags, Shandong Xinshidai Pharmaceutical Co., Ltd.) 1 bag at a time, 3 times a day, with boiled water.

[0157] Each group received 2 courses of treatment, each course lasting 7 days.

[0158] 3. Efficacy standards

[0159] Cured: No more nasal itching, nasal congestion, paroxysmal sneezing and watery runny nose;

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

[0161] Ineffective: The frequency of nasal itching, nasal congestion, paroxysmal sneezing and watery runny nose has not improved or has decreased by less than 50% compared with before treatment.

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

[0163] Table 3 The therapeutic effects of the embodiment group, comparative example group and positive group

[0164] Group Cured cases Effective Examples Invalid example Total effective rate (%) Example Group 33 14 3 94 Comparative group 24 20 6 88 Positive group 18 27 5 90

[0165] As can be seen from the data in Table 3, the Example 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 comparative example group and the positive group.

[0166] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A compound Chinese medicine composition for treating allergic rhinitis, characterized in that: The invention comprises the following raw materials in parts by weight: 20-30 parts of Antrodia cinnamomea, 10-20 parts of Cortex Moutan, 5-10 parts of Cynanchum chinense, 5-10 parts of Periostracum cicadae, 1-3 parts of Bezoar, 0.5-1 part of Borneolum Syntheticum and 5-10 parts of Menthol.

2. Use of the compound Chinese medicine composition according to claim 1 in preparing a medicine for treating allergic rhinitis.

3. The use according to claim 2, characterized in that The dosage form of the medicine is decoction, pill, powder, granule, capsule, tablet, oral liquid, ointment, syrup, spray, and gel.

4. The use according to claim 3, characterized in that The preparation method of the spray comprises the following steps: drying and crushing Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and mint, adding an ethanol solution, ultrasonically immersing the mixture, performing reflux extraction, filtering, concentrating under reduced pressure and drying the mixture to obtain a Chinese medicine powder; encapsulating borneol with β-cyclodextrin, drying the mixture and crushing the mixture to obtain a borneol-β-CD inclusion complex; crushing bezoar, mixing the mixture with the Chinese medicine powder, the borneol-β-CD inclusion complex, a solvent, an isotonicity regulator, a thickener, a preservative, an antioxidant and water, and filtering the mixture to obtain the spray.

5. The use according to claim 4, characterized in that The volume percentage of the ethanol solution is 60%-70%, the power of ultrasonic immersion is 200-300W, the frequency is 20-30kHz, and the time is 25-35min.

6. The use according to claim 4 or 5, characterized in that The material-liquid ratio of the reflux extraction is 1:8-10 g / mL, the temperature is 70-80° C., and the number of extractions is 1-3 times, each time for 40-60 minutes.

7. The use according to claim 3, characterized in that The preparation method of the granules comprises the following steps: drying and crushing Antrodia cinnamomea, Cortex Moutan, Cynanchum chinense, Periostracum cicadae and Menthol, mixing the mixture with water, sequentially adding xylanase, β-glucosidase and ficin for ultrasonic enzymolysis, filtering to obtain an enzymatic hydrolyzate, adding glucose, inoculating composite microorganisms for anaerobic fermentation, filtering to obtain a fermentation liquid, concentrating under reduced pressure, spray drying to obtain a fermentation dry extract powder; encapsulating borneol with β-cyclodextrin, drying and crushing to obtain a borneol-β-CD inclusion complex; and crushing bezoar, mixing the crushed bezoar with the fermentation dry extract powder, the borneol-β-CD inclusion complex, a filler, a disintegrant, a lubricant and a flavoring agent, and granulating to obtain the granules.

8. The use according to claim 7, characterized in that The amount of xylanase added is 0.3%-0.8% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, the enzymolysis temperature is 40-50°C, 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 the Antrodia cinnamomea, Moutan bark, Cynanchum indica, cicada slough and mint, and the enzymolysis temperature is 40-50°C. , pH value is 5-6, ultrasonic power is 200-300W, frequency is 20-30kHz, and time is 40-60min; the addition amount of the ficin is 0.2%-0.5% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum chinense, cicada shell and mint, the enzymolysis temperature is 37-40℃, pH value is 7-8, ultrasonic power is 200-300W, frequency is 20-30kHz, and time is 30-40min.

9. The use according to claim 7, characterized in that The inclusion process comprises: dissolving β-cyclodextrin in water to obtain a β-cyclodextrin aqueous solution, dissolving borneol in anhydrous ethanol to obtain a borneol ethanol solution, slowly adding the borneol ethanol solution dropwise into the β-cyclodextrin aqueous solution, stirring in a water bath at 35-45° C. for 1-2 hours, standing to precipitate, filtering, and drying the precipitate to obtain a borneol-β-CD inclusion complex.

10. The use according to claim 7, characterized in that The fermented composite microorganisms are composed of animal Bifidobacterium lactis subspecies and digestive-associated Lactobacillus in a weight ratio of 1-3:2-5. The added amount of the composite microorganisms is 0.8%-1.2% of the total mass of the Antrodia cinnamomea, Moutan bark, Cynanchum chinense, cicada slough and mint. The fermentation temperature is 35-40°C, the pH value is 6-7, and the fermentation time is 24-72h.