Composition for treating obstructive sleep apnea-hypopnea syndrome, granule preparation and preparation method thereof

Abstract

The present invention provides a composition for treating obstructive sleep apnea hypopnea syndrome, a granule preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparations. The composition provided by the present invention is prepared from 5-10g of Astragalus, 1-3g of Atractylodes macrocephala, 1-2g of dried orange peel, 3-8g of Cimicifuga heracleifolia, 3-6g of Bupleurum, 3-5g of Scutellaria baicalensis, 2-4g of raw sun-dried ginseng, 2-4g of roasted licorice, 1-4g of Mentha, 2-6g of Burdock fruit, 2-8g of Bombyx batryticatus, 2-4g of Periostracum cicadae, 1-4g of Ligusticum chuanxiong, 4-8g of Curcuma aromatica, 5-10g of Acorus calamus, 2-6g of Salvia miltiorrhiza, 2-5g of Pinellia ternata, 1-4g of Poria cocos and 1-4g of Paeonia lactiflora. The present invention greatly reduces the amount of each raw material used in the composition, and by adjusting the ratio of each raw material and improving the preparation process, the effect of significantly treating obstructive sleep apnea hypopnea syndrome with good efficacy and fast onset is finally achieved on the basis of significantly reducing the cost.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine preparations, and in particular relates to a composition for treating obstructive sleep apnea-hypopnea syndrome, a granule preparation and a preparation method thereof. Background Art

[0002] Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep-related respiratory disorder of unknown etiology, characterized by intermittent apnea and / or reduced ventilation during sleep, with the main manifestations of snoring at night, daytime sleepiness, fatigue, etc. The repetitive intermittent hypoxia caused by the intermittent apnea and / or hypopnea during sleep is similar to the mechanism of ischemia / reperfusion injury, which can cause systemic oxidative stress, inflammatory response and increased sympathetic nerve activity, leading to a variety of complications involving multiple systems such as cardiovascular and cerebrovascular, nervous, endocrine, urogenital, digestive, and blood. Recurrent nocturnal hypoxia and hypercapnia caused by apnea can lead to complications such as hypertension, coronary heart disease, diabetes, and cerebrovascular disease, as well as traffic accidents, and even sudden death at night. Therefore, OSAHS is a potentially fatal sleep-related respiratory disorder.

[0003] Due to the complex etiology and lesion sites of OSAHS, there is no method that can treat all OSAHS patients. At present, there are many Western medicine drugs for the treatment of snoring. Acetazolamide and thyroxine tablets promote metabolism and have certain effects. They can relieve the symptoms during medication, but cannot cure it. Although there are relevant reports on the treatment of OSAHS with traditional Chinese medicine preparations, most of them have problems such as poor efficacy, long time required for onset of effect and high cost. Therefore, there is an urgent need to provide a traditional Chinese medicine preparation with good efficacy, fast onset and low cost in this field. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a Chinese medicine composition with good efficacy, rapid onset of effect and low cost and a preparation method thereof.

[0005] Another object of the present invention is to provide a Chinese medicine granule preparation with good efficacy, rapid onset of effect and low cost and a preparation method thereof.

[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 composition for treating obstructive sleep apnea-hypopnea syndrome. The composition is prepared from the following raw materials: 5-10g of astragalus, 1-3g of atractylodes, 1-2g of dried tangerine peel, 3-8g of cimicifuga, 3-6g of bupleurum, 3-5g of scutellaria, 2-4g of raw sun-dried ginseng, 2-4g of roasted liquorice, 1-4g of mint, 2-6g of burdock fruit, 2-8g of bombyx batryticatus, 2-4g of cicada shell, 1-4g of ligusticum chuanxiong, 4-8g of curcuma, 5-10g of calamus, 2-6g of salvia miltiorrhiza, 2-5g of pinellia tuber, 1-4g of tuckahoe and 1-4g of white peony root.

[0008] The present invention also provides a preparation method of the above-mentioned composition, comprising the following steps: mixing astragalus, atractylodes, dried orange peel and cimicifuga to obtain a mixture 1, mixing the mixture 1 with an ethanol solution with a volume fraction of 40% to 50% and performing reflux extraction to obtain a reflux extract 1; mixing bupleurum, scutellaria, raw sun-dried ginseng, roasted liquorice and mint to obtain a mixture 2, mixing the mixture 2 with water and soaking it, then boiling it, keeping it boiling for 15min to 25min, filtering and taking the filtrate as a decoction liquid; mixing burdock fruit, bombyx batryticatus, cicada shell, ligusticum chuanxiong and curcuma to obtain a mixture 3, mixing the mixture 3 with water and soaking it, then boiling it, keeping it boiling for 30min to 40min, filtering and taking the filtrate as a decoction liquid. liquid, adding anhydrous ethanol until the concentration of the ethanol solution is 50% to 60%, filtering to remove impurities, taking the filtrate to recover ethanol, and obtaining extract 1; mixing extract 1 with anhydrous ethanol until the concentration of the ethanol solution is 80% to 90%, filtering to remove impurities, taking the filtrate to recover ethanol, and obtaining extract 2; mixing Acorus calamus, Salvia miltiorrhiza, Pinellia ternata, Poria cocos and Paeonia lactiflora to obtain mixture 4, mixing mixture 4 with water and a composite enzyme for enzymolysis, and heating the enzymolysis solution for reflux extraction to obtain reflux extract 2; the composite enzyme consists of cellulase and pectinase; mixing the reflux extract 1, the decoction, the extract 2 and the reflux extract 2, concentrating them into an extract, and drying and crushing them to obtain the composition.

[0009] Preferably, the weight-to-volume ratio of the mixture 1 to the ethanol solution with a volume fraction of 40% to 50% is 1 g: 8 to 12 mL.

[0010] Preferably, the soaking time is 20 min to 30 min.

[0011] Preferably, the weight-to-volume ratio of the mixture 2 to water is 1 g: 5-8 mL, and the weight-to-volume ratio of the mixture 3 to water is 1 g: 7-10 mL.

[0012] Preferably, the temperature of the enzymolysis is 35° C. to 45° C., the time of the enzymolysis is 30 min to 50 min, and the pH value of the enzymolysis is 3.5 to 6.5.

[0013] Preferably, the dosage of the complex enzyme is 0.06 g to 0.09 g of the complex enzyme per 1 g of the mixture 4, and the weight ratio of the cellulase to the pectinase is 1:2 to 3.

[0014] The present invention also provides a granule preparation for treating obstructive sleep apnea-hypopnea syndrome, which consists of the above composition and auxiliary materials.

[0015] Preferably, the weight ratio of the composition to the auxiliary materials is 1:1.5-3.

[0016] The present invention also provides a method for preparing the granule preparation, comprising the following steps: mixing the composition with auxiliary materials, and then performing dry granulation to obtain the granule preparation.

[0017] Beneficial effects of the present invention:

[0018] The present invention significantly reduces the dosage of each raw material in the composition on the basis of ensuring that the obstructive sleep apnea hypopnea syndrome can be treated, and by adjusting the ratio of each raw material and improving the preparation process, the present invention achieves a significant effect of treating obstructive sleep apnea hypopnea syndrome with good efficacy and rapid onset on the basis of significantly reducing the cost. The present invention has the advantages of treating both the symptoms and the root cause, replenishing the lung qi, raising the spleen yang qi, clearing the lung heat, activating blood circulation, cooling blood and dispersing depression to open the throat, thereby benefiting the ancestral qi to circulate qi and blood and regulate breathing.

[0019] The composition and granule preparation of the present invention can achieve the effects of promoting qi, cooling blood and dispersing blood stasis, clearing phlegm and opening the throat, promoting blood circulation, removing dampness, resolving phlegm and dispersing stagnation, and detoxifying and relieving sore throat and opening the orifices. At the same time, the composition and granule preparation of the present invention can achieve the effect of treating OSAHS by reducing the concentration levels of HIF-1α, IFN-γ and IL-4. The composition and granule preparation of the present invention have an anti-inflammatory effect by inhibiting the expression of NF-κB in the nasal mucosa. The cure rate of the composition and granule preparation of the present invention for obstructive sleep apnea hypopnea syndrome can reach more than 90%, and it is safe and has no side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Comparison results of HIF-1α, IFN-γ, and IL-4 levels in the serum of mice in each group;

[0021] Figure 2 The results are as follows: the percentage of NF-κB positive area in each group of mice;

[0022] Figure 3 The results are the expression changes of NF-κB mRNA in mouse nasal mucosa tissue;

[0023] Figure 4 is the change of rat food intake (g / d);

[0024] Figure 5 is the weight change of rats (g). DETAILED DESCRIPTION

[0025] The invention provides a composition for treating obstructive sleep apnea-hypopnea syndrome. The composition is prepared from the following raw materials: 5-10g of astragalus, 1-3g of atractylodes, 1-2g of dried tangerine peel, 3-8g of cimicifuga, 3-6g of bupleurum, 3-5g of scutellaria, 2-4g of raw sun-dried ginseng, 2-4g of roasted liquorice, 1-4g of mint, 2-6g of burdock fruit, 2-8g of bombyx batryticatus, 2-4g of cicada shell, 1-4g of ligusticum chuanxiong, 4-8g of curcuma, 5-10g of calamus, 2-6g of salvia miltiorrhiza, 2-5g of pinellia tuber, 1-4g of tuckahoe and 1-4g of white peony root.

[0026] The present invention proposes a composition for treating obstructive sleep apnea hypopnea syndrome (snoring) under the guidance of the "Zongqi" theory. The theoretical basis for using "Zongqi" to treat snoring is that the composition of Zongqi includes two parts: one is the fresh air inhaled by the lungs, and the other is the water and grain essence absorbed by the spleen and stomach. The function of Zongqi: to control breathing by running through the respiratory tract, and to circulate qi and blood through the heart meridian. "Lingshu Xieke" says: Zongqi accumulates in the chest and comes out of the throat to circulate qi through the heart meridian. If the lung qi is deficient, the function of the lung to inhale fresh air is weakened; if the spleen qi is deficient, the spleen and stomach functions are damaged, and the transportation and transformation are abnormal, it is easy to produce phlegm and dampness, qi deficiency and phlegm obstruction, and blood stasis is formed over time. Phlegm, qi and blood stasis are blocked in the throat. The spleen is also the main muscle. The throat muscles are weak and relaxed, and snoring is progressively aggravated. Therefore, it can replenish lung qi, raise spleen yang qi, activate blood circulation, cool blood and dissipate depression to open throat orifices, thus benefiting zongqi to circulate qi and blood, regulate breathing, and clear phlegm, blood stasis and qi obstruction in the throat of snoring patients from the source, thus improving snoring symptoms. According to this etiology and pathogenesis, syndrome differentiation and disease differentiation are formed, rather than just replenishing the middle and replenishing qi on the surface.

[0027] The syndrome differentiation of the composition of the present invention is: spleen yang deficiency, endogenous dampness and turbidity, and phlegm and blood stasis blocking the collaterals. Etiology and pathogenesis analysis: due to fatigue from eating and drinking, spleen yang deficiency, spleen and stomach weakness, dampness and heat accumulation over time, damp heat retention, obstruction of qi, excess qi is fire, then burning body fluid produces phlegm, phlegm and blood stasis blocking the collaterals cause qi dysfunction, throat orifice is unfavorable, and snoring occurs. Weak spleen and stomach, phlegm and blood stasis blocking the collaterals will show fatigue and love to lie down, chest and diaphragm fullness, limbs are heavy, or dizziness, palpitations, headache, tasteless food, indigestion; long-term accumulation of heat will show throat discomfort or redness and swelling, bitter mouth and dry tongue; phlegm and heat accumulation in the lungs will show coughing and expectoration; damp heat will show irregular bowel movements and frequent urination; white and slippery or greasy tongue coating, slippery and astringent or deep and fine pulse, all of which are signs of spleen yang deficiency and phlegm and blood stasis blocking the collaterals.

[0028] The prescription of the composition of the present invention is explained as follows: Astragalus, invigorates the spleen and replenishes the middle, raises yang and lifts the sunken, removes toxins and promotes muscle growth, replenishes qi and nourishes blood, and is mainly used to treat lung and spleen qi deficiency. Raw sun-dried ginseng nourishes the five internal organs and calms the spirit. Atractylodes macrocephala, invigorates the spleen and replenishes qi, treats wind-cold dampness arthralgia, removes dead muscles, eliminates phlegm and water, and benefits body fluids. Astragalus, raw sun-dried ginseng (ginseng), and Atractylodes macrocephala are all monarch drugs, which invigorate the spleen qi and benefit the lung qi, so as to facilitate the generation and operation of zongqi. Cimicifuga, Bupleurum, Tangerine peel, Pinellia, and Poria raise yang, invigorate the spleen, regulate qi and eliminate dampness, while Scutellaria and White Peony Root clear and purge lung heat, and astringe yin and harmonize the camp, and are all minister drugs to benefit zongqi. Curcuma, Chuanxiong, and Salvia miltiorrhiza are used to promote qi, cool blood and disperse blood stasis, Acorus gramineus can clear phlegm and open the throat, promote blood circulation and eliminate dampness, Bombyx batryticatus, cicada shell, burdock fruit, and mint can resolve phlegm and disperse knots, detoxify and relieve throat and open the orifices; Licorice harmonizes the various drugs. In summary, the method can treat both the symptoms and the root causes, replenish the lung qi, raise the spleen yang qi, and at the same time clear the lung heat, activate blood circulation, cool the blood and relieve depression to open the throat, thereby benefiting the ancestral qi to circulate qi and blood, regulate breathing, and clear the phlegm, blood stasis and qi obstruction in the throat of snoring patients from the source, improve the symptoms of snoring, and achieve an effective treatment effect. At the same time, the medicinal materials selected for the prescription of the present invention are all non-toxic Chinese medicinal materials, and the prepared composition does not produce acute toxicity.

[0029] In the present invention, the composition is preferably made of the following raw materials: 6-8g of Astragalus, 2g of Atractylodes, 2g of Tangerine Peel, 4-6g of Cimicifuga, 4-5g of Bupleurum, 4g of Scutellaria, 3g of Raw Sun-dried Ginseng, 3g of Roasted Licorice, 3g of Mentha, 3g of Burdock Fruit, 3-6g of Bombyx Batryticatus, 3g of Cicada Periostracum, 2-3g of Chuanxiong, 5-6g of Curcuma, 6-8g of Acorus Calamus, 3-5g of Salvia Miltiorrhiza, 3-4g of Pinellia Ternate g, Poria 2-3g and White Peony 2-3g; more preferably, it is made from the following raw materials: Astragalus 7g, Atractylodes 2g, Tangerine Peel 2g, Cimicifuga 5g, Bupleurum 4g, Scutellaria 4g, Raw Sun-dried Ginseng 3g, Roasted Licorice 3g, Mentha 3g, Burdock Fructus 4g, Bombyx Batryticatus 4-5g, Periostracum Cicadae 3g, Chuanxiong 2g, Curcuma 5g, Acorus Gramineus 7g, Salvia 4g, Pinellia 3g, Poria 2g and White Peony 2g. The present invention has no special restrictions on the specific sources of the above raw materials, and conventional commercial products in the field can be used.

[0030] The present invention also provides a preparation method of the above-mentioned composition, comprising the following steps: mixing astragalus, atractylodes, dried orange peel and cimicifuga to obtain a mixture 1, mixing the mixture 1 with an ethanol solution with a volume fraction of 40% to 50% and performing reflux extraction to obtain a reflux extract 1; mixing bupleurum, scutellaria, raw sun-dried ginseng, roasted liquorice and mint to obtain a mixture 2, mixing the mixture 2 with water and soaking it, then boiling it, keeping it boiling for 15min to 25min, filtering and taking the filtrate as a decoction liquid; mixing burdock fruit, bombyx batryticatus, cicada shell, ligusticum chuanxiong and curcuma to obtain a mixture 3, mixing the mixture 3 with water and soaking it, then boiling it, keeping it boiling for 30min to 40min, filtering and taking the filtrate as a decoction liquid. liquid, adding anhydrous ethanol until the concentration of the ethanol solution is 50% to 60%, filtering to remove impurities, taking the filtrate to recover ethanol, and obtaining extract 1; mixing extract 1 with anhydrous ethanol until the concentration of the ethanol solution is 80% to 90%, filtering to remove impurities, taking the filtrate to recover ethanol, and obtaining extract 2; mixing Acorus calamus, Salvia miltiorrhiza, Pinellia ternata, Poria cocos and Paeonia lactiflora to obtain mixture 4, mixing mixture 4 with water and a composite enzyme for enzymolysis, and heating the enzymolysis solution for reflux extraction to obtain reflux extract 2; the composite enzyme consists of cellulase and pectinase; mixing the reflux extract 1, the decoction, the extract 2 and the reflux extract 2, concentrating them into an extract, and drying and crushing them to obtain the composition.

[0031] In the preparation method of the present invention, it is preferred that all the medicinal flavors in the composition are crushed before the effective ingredients are extracted. The present invention does not specifically limit the method of crushing, but preferably grinding and crushing, and then passing through a 50-100 mesh sieve. In the preparation method of the present invention, the weight-to-volume ratio of the mixture 1 to the ethanol solution with a volume fraction of 40% to 50% is preferably 1g:8 to 12mL, more preferably 1g:9 to 11mL, and most preferably 1g:10mL. In the present invention, the concentration (volume fraction) of the ethanol solution of the reflux extract 1 is preferably 45%, the number of reflux extractions is preferably 2 to 3 times, and the time for each reflux extraction is preferably 0.5h to 1h. When performing the second or third reflux extraction, the amount of ethanol solution added is half of the amount of ethanol solution added in the previous reflux extraction.

[0032] In the present invention, the weight volume ratio of mixture 2 to water is preferably 1g:5-8mL, more preferably 1g:6-7mL. After mixing mixture 2 with water, it needs to be soaked, and the soaking time is preferably 20min-30min, more preferably 25min-28min. After the soaking is completed, it is boiled, and the decoction needs to be kept in a boiling state after boiling, and the boiling time is preferably 18min-22min, more preferably 19min-20min.

[0033] In the present invention, the weight volume ratio of mixture 3 to water is preferably 1g:7-10mL, more preferably 1g:8-9mL. After mixing mixture 3 with water, it is necessary to soak, and the soaking time is preferably 20min-30min, more preferably 25min-28min. After the soaking is completed, it is decocted, and the decoction is boiled and needs to be kept in a boiling state, and the boiling time is preferably 33min-37min, more preferably 35min-36min. Take the filtrate obtained after decoction, and carry out the alcohol precipitation step, preferably add anhydrous ethanol to the concentration of the ethanol solution is 55%, remove the alcohol precipitation part, take the filtrate to recover ethanol, the present invention does not specifically limit the specific method of recovering ethanol, and the conventional method of recovering ethanol after water extraction and alcohol precipitation in the field can be used. After obtaining extract 1, extract 1 is mixed with anhydrous ethanol to a concentration of ethanol solution preferably 85%, and after removing the alcohol precipitation part, the method of recovering ethanol is the same as above, which will not be repeated here.

[0034] In the present invention, the weight ratio of cellulase and pectinase in the complex enzyme is preferably 1:2-3, the dosage of the complex enzyme is preferably 0.07g-0.08g per 1g of mixture 4, the weight volume ratio of the mixture 4 to water is preferably 1g:8ml-10ml, the temperature of the enzymatic hydrolysis is preferably 35°C-45°C, more preferably 38°C-40°C, the time of the enzymatic hydrolysis is preferably 30min-50min, more preferably 35min-45min, the pH value of the enzymatic hydrolysis is preferably 3.5-6.5, more preferably 4.5-5.5. In the present invention, when the enzymatic hydrolyzate is subjected to reflux extraction, the number of reflux extractions is preferably 2 times, and the time of each reflux extraction is preferably 20min-30min.

[0035] In the preparation method of the present invention, the methods of obtaining the above-mentioned reflux extract 1, decoction, extract 2 and reflux extract 2 respectively are not in any particular order. After obtaining the above-mentioned four substances, they are mixed and concentrated. The present invention has no special limitation on the specific method of concentration. The conventional method of concentrating to extract in the art can be used. The drying temperature is preferably 40°C to 50°C, and the composition is obtained by drying until the water content is less than 10%.

[0036] The preparation method of the invention specifically obtains 40% to 50% alcohol-soluble components of astragalus, atractylodes, dried orange peel and cimicifuga, water-soluble and non-volatile components of bupleurum, scutellaria, raw sun-dried ginseng, roasted liquorice and mint, water-soluble but 50% to 60% and 80% to 90% alcohol-soluble components of burdock fruit, bombyx batryticatus, cicada shell, ligusticum chuanxiong and curcuma, and enzymatically hydrolyzed water-soluble and non-volatile components of calamus, salvia miltiorrhiza, pinellia tuber, poria and white peony root, so that components that are not conducive to the final medicinal effect can be removed, and the dissolution rate of beneficial components is greatly improved. In the process of mixing and extracting the components, the active components of the medicinal flavors interact with each other, so that a significant therapeutic effect can be achieved on the basis of greatly reducing the amount of raw materials.

[0037] The present invention also provides a granule preparation for treating obstructive sleep apnea-hypopnea syndrome, which is composed of the above composition and auxiliary materials. In the granule preparation of the present invention, the above composition is used in a dosage of one dose, and one dose of the dosage is sufficient per day.

[0038] In the present invention, the weight ratio of the composition to the auxiliary material is preferably 1:1.5-3, more preferably 1:2.5. In the present invention, the auxiliary material preferably includes at least one of sucralose and dextrin.

[0039] The present invention also provides a method for preparing the above granular preparation, comprising the following steps: mixing the composition with auxiliary materials, and then performing dry granulation to obtain the granular preparation. The present invention has no particular limitation on the specific method of dry granulation, and any conventional dry granulation method in the art can be used.

[0040] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0041] In the following embodiments, unless otherwise specified, all of them are conventional methods.

[0042] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0043] Example 1

[0044] A composition for treating obstructive sleep apnea-hypopnea syndrome is prepared from the following raw materials: 7g of Astragalus, 2g of Atractylodes macrocephala, 2g of dried tangerine peel, 5g of Cimicifuga heracleifolia, 5g of Bupleurum chinense, 4g of Scutellaria baicalensis, 3g of raw sun-dried ginseng, 3g of roasted liquorice, 3g of peppermint, 4g of Arctium lappa, 5g of Bombyx batryticatus, 3g of Periostracum cicadae, 2g of Ligusticum chuanxiong, 5g of Curcuma aromatica, 7g of Acorus calamus, 4g of Salvia miltiorrhiza, 3g of Pinellia ternata, 2g of Poria and 2g of White Peony Root.

[0045] Example 2

[0046] A composition for treating obstructive sleep apnea-hypopnea syndrome is prepared from the following raw materials: 5g of astragalus, 1g of atractylodes, 1g of dried tangerine peel, 3g of cimicifuga, 3g of bupleurum, 3g of scutellaria, 2g of raw sun-dried ginseng, 2g of roasted liquorice, 1g of mint, 2g of burdock fruit, 2g of bombyx batryticatus, 2g of cicada shell, 1g of ligusticum chuanxiong, 4g of curcuma, 5g of calamus, 2g of salvia miltiorrhiza, 2g of pinellia tuber, 1g of tuckahoe and 1g of white peony root.

[0047] Example 3

[0048] A composition for treating obstructive sleep apnea-hypopnea syndrome is prepared from the following raw materials: 10g of astragalus, 3g of atractylodes, 2g of dried tangerine peel, 8g of cimicifuga, 6g of bupleurum, 5g of scutellaria, 4g of raw sun-dried ginseng, 4g of roasted liquorice, 4g of peppermint, 6g of burdock fruit, 8g of bombyx batryticatus, 4g of cicada shell, 4g of ligusticum chuanxiong, 8g of curcuma, 10g of calamus, 6g of salvia miltiorrhiza, 5g of pinellia tuber, 4g of tuckahoe and 4g of white peony root.

[0049] Example 4

[0050] The composition for treating obstructive sleep apnea-hypopnea syndrome described in Example 1 is prepared by the following steps: the raw materials described in Example 1 are crushed by a grinder, and then passed through a 50-mesh sieve to obtain raw material powders. The raw material powders are accurately weighed according to the amount of the raw material powders described in Example 1, and the following process is performed:

[0051] Mixing Astragalus, Atractylodes macrocephala, Tangerine peel and Cimicifuga to obtain a mixture 1, mixing the mixture 1 with an ethanol solution having a volume fraction of 45% at a weight volume ratio of 1 g: 9 mL, performing a first reflux extraction for 0.6 h, taking the reflux extract and adding an ethanol solution having a volume fraction of 45% (adding the mixture 1 to the ethanol solution having a volume fraction of 45% at a weight volume ratio of 1 g: 4.5 mL) to perform a second reflux extraction for 0.5 h to obtain a reflux extract 1;

[0052] Bupleurum, Scutellaria, raw sun-dried ginseng, roasted liquorice and mint were mixed to obtain mixture 2, and mixture 2 was mixed with water at a weight volume ratio of 1 g: 6 mL, soaked for 25 minutes, and then decocted, kept boiling for 19 minutes after boiling, and the filtrate was filtered and recorded as decoction liquid;

[0053] The mixture 3 is mixed with burdock seeds, silkworm pupa, cicada shell, chuanxiong and curcuma, and the mixture 3 is mixed with water in a weight volume ratio of 1 g: 9 mL, and then soaked for 25 minutes, and then decocted, boiled and kept boiling for 35 minutes, filtered, and the filtrate is taken, and anhydrous ethanol is added to the ethanol solution to have a concentration of 55%, filtered to remove impurities, and the filtrate is taken to recover ethanol to obtain extract 1, and the extract 1 is mixed with anhydrous ethanol to have a concentration of 85% of the ethanol solution, filtered to remove impurities, and the filtrate is taken to recover ethanol to obtain extract 2;

[0054] Acorus calamus, salvia miltiorrhiza, pinellia tuber, poria and white peony root are mixed to obtain mixture 4, and mixture 4 is mixed with water and composite enzyme for enzymolysis (mixture 4: water: composite enzyme = 1g: 9ml: 0.07g, the weight ratio of cellulase and pectinase in the composite enzyme is 1:3), the enzymolysis temperature is 38°C, the enzymolysis time is 35min, the enzymolysis pH value is 4.5, after the enzymolysis is completed, the enzymolysis solution is heated and refluxed for extraction once, the reflux extraction time is 25min, and the reflux extract is taken to obtain reflux extract 2;

[0055] The reflux extract 1, decoction, extract 2 and reflux extract 2 obtained above are mixed, concentrated into an extract, dried at 40° C. until the water content is less than 10%, and pulverized to obtain the composition.

[0056] Example 5

[0057] The composition for treating obstructive sleep apnea-hypopnea syndrome described in Example 1 is prepared by the following steps: the raw medicinal ingredients described in Example 1 are respectively crushed by a grinder, and then passed through a 100-mesh sieve to obtain raw material powders.

[0058] According to the amount of each raw material medicinal flavor recorded in Example 1, each raw material powder is accurately weighed and the following process is carried out:

[0059] Mixing Astragalus, Atractylodes macrocephala, Tangerine peel and Cimicifuga to obtain a mixture 1, mixing the mixture 1 with a 40% ethanol solution at a weight-to-volume ratio of 1 g:8 mL, performing a first reflux extraction for 0.5 h, taking the reflux extract and adding a 40% ethanol solution (adding the mixture 1 to the 40% ethanol solution at a weight-to-volume ratio of 1 g:4 mL) to perform a second reflux extraction for 0.5 h to obtain a reflux extract 1;

[0060] Bupleurum, Scutellaria, raw sun-dried ginseng, roasted liquorice and mint were mixed to obtain mixture 2, and mixture 2 was mixed with water at a weight volume ratio of 1 g: 5 mL, soaked for 20 minutes, and then decocted, kept boiling for 18 minutes after boiling, and the filtrate was filtered and recorded as decoction liquid;

[0061] The mixture 3 is mixed with burdock seeds, silkworm pupa, cicada shell, chuanxiong and curcuma, and the mixture 3 is mixed with water in a weight volume ratio of 1 g: 7 mL, and the mixture is soaked for 20 minutes, then decocted, boiled and kept boiling for 25 minutes, filtered, the filtrate is taken, anhydrous ethanol is added to the ethanol solution to a concentration of 50%, filtered to remove impurities, the filtrate is taken to recover ethanol, and extract 1 is obtained, the extract 1 is mixed with anhydrous ethanol to a concentration of 80% of the ethanol solution, filtered to remove impurities, and the filtrate is taken to recover ethanol, and extract 2 is obtained;

[0062] Acorus calamus, salvia miltiorrhiza, pinellia tuber, poria and white peony root are mixed to obtain mixture 4, and mixture 4 is mixed with water and composite enzyme for enzymolysis (mixture 4: water: composite enzyme = 1g: 8ml: 0.08g, the weight ratio of cellulase and pectinase in the composite enzyme is 1:2), the enzymolysis temperature is 35°C, the enzymolysis time is 30min, the enzymolysis pH value is 3.5, after the enzymolysis is completed, the enzymolysis solution is heated and refluxed for extraction once, the reflux extraction time is 20min, and the reflux extract is taken to obtain reflux extract 2;

[0063] The reflux extract 1, decoction, extract 2 and reflux extract 2 obtained above are mixed, concentrated into an extract, dried at 45° C. until the water content is less than 10%, and pulverized to obtain the composition.

[0064] Example 6

[0065] The composition for treating obstructive sleep apnea-hypopnea syndrome described in Example 1 is prepared by the following steps: the raw materials described in Example 1 are crushed by a grinder, and then passed through a 50-mesh sieve to obtain raw material powders. The raw material powders are accurately weighed according to the amount of the raw material powders described in Example 1, and the following process is performed:

[0066] Mixing Astragalus, Atractylodes macrocephala, Tangerine peel and Cimicifuga to obtain a mixture 1, mixing the mixture 1 with a 50% ethanol solution at a weight volume ratio of 1 g: 12 mL, performing a first reflux extraction for 1 h, taking the reflux extract and adding a 50% ethanol solution (adding the mixture 1 to the 50% ethanol solution at a weight volume ratio of 1 g: 6 mL) to perform a second reflux extraction, the extraction time is 1 h, and obtaining a reflux extract 1;

[0067] Bupleurum, Scutellaria, raw sun-dried ginseng, roasted liquorice and mint were mixed to obtain mixture 2, and mixture 2 was mixed with water at a weight volume ratio of 1 g: 8 mL, soaked for 30 minutes, and then decocted, kept boiling for 22 minutes after boiling, and the filtrate was filtered and recorded as decoction liquid;

[0068] The mixture 3 is mixed with burdock seeds, silkworm pupa, cicada shell, chuanxiong and curcuma, and the mixture 3 is mixed with water in a weight volume ratio of 1 g: 10 mL, and then soaked for 30 minutes, and then decocted, boiled and kept boiling for 40 minutes, filtered, and the filtrate is taken, anhydrous ethanol is added to the ethanol solution to a concentration of 60%, filtered to remove impurities, and the filtrate is taken to recover ethanol to obtain extract 1, and the extract 1 is mixed with anhydrous ethanol to a concentration of 90% of the ethanol solution, filtered to remove impurities, and the filtrate is taken to recover ethanol to obtain extract 2;

[0069] Acorus calamus, salvia miltiorrhiza, pinellia tuber, poria and white peony root are mixed to obtain mixture 4, and mixture 4 is mixed with water and composite enzyme for enzymolysis (mixture 4: water: composite enzyme = 1g: 10ml: 0.08g, the weight ratio of cellulase and pectinase in the composite enzyme is 1:2), the enzymolysis temperature is 45°C, the enzymolysis time is 50min, the enzymolysis pH value is 6.5, after the enzymolysis is completed, the enzymolysis solution is heated and refluxed for extraction once, the reflux extraction time is 30min, and the reflux extract is taken to obtain reflux extract 2;

[0070] The reflux extract 1, decoction, extract 2 and reflux extract 2 obtained above are mixed, concentrated into an extract, dried at 50° C. until the water content is less than 10%, and pulverized to obtain the composition.

[0071] Example 7

[0072] The composition for treating obstructive sleep apnea-hypopnea syndrome described in Example 2 is prepared by the preparation method described in Example 4.

[0073] Example 8

[0074] The composition for treating obstructive sleep apnea-hypopnea syndrome described in Example 3 is prepared by the preparation method described in Example 4.

[0075] Example 9

[0076] The composition prepared in Example 4 was mixed with an auxiliary material (dextrin) at a weight ratio of 1:1.5, and a granular preparation for treating obstructive sleep apnea hypopnea syndrome was obtained by dry granulation, which was packaged into bags (the composition in Example 4 was used for 1 bag).

[0077] Example 10

[0078] The composition prepared in Example 4 was mixed with an auxiliary material (dextrin) at a weight ratio of 1:3, and a granular preparation for treating obstructive sleep apnea hypopnea syndrome was obtained by dry granulation, which was packaged into bags (the composition in Example 4 was used for 1 bag).

[0079] Embodiment 11

[0080] The composition prepared in Example 4 was mixed with an auxiliary material (dextrin) at a weight ratio of 1:2.5, and a granular preparation for treating obstructive sleep apnea hypopnea syndrome was obtained by dry granulation, which was packaged into bags (the composition in Example 4 was used for 1 bag).

[0081] Example 12

[0082] The composition prepared in Example 5 was mixed with an auxiliary material (dextrin) at a weight ratio of 1:1.5, and then a granular preparation for treating obstructive sleep apnea-hypopnea syndrome was obtained by dry granulation.

[0083] Embodiment 13

[0084] The composition prepared in Example 6 was mixed with an auxiliary material (dextrin) at a weight ratio of 1:1.5, and then a granular preparation for treating obstructive sleep apnea-hypopnea syndrome was obtained by dry granulation.

[0085] Comparative Example 1

[0086] The difference from Example 1 is that the amount of each raw material in the composition is different, specifically: 18g Astragalus, 10g Atractylodes, 15g Tangerine Peel, 10g Cimicifuga, 9g Bupleurum, 6g Scutellaria, 6g Raw Sun-dried Ginseng, 10g Roasted Licorice, 3g Menthol, 10g Burdock Fruit, 9g Bombyx Batryticatus, 6g Cicada Periostracum, 10g Chuanxiong, 20g Curcuma, 15g Acorus Gramineus, 9g Salvia Miltiorrhiza, 9g Pinellia, 10g Poria and 9g White Peony.

[0087] The preparation method adopts water decoction extraction method:

[0088] According to the weight of each medicinal ingredient in this comparative ratio, 19 medicinal materials are accurately weighed, water is added to soak the medicinal surfaces, and then 8 times the amount of water is added, and the extraction is performed by heating and reflux twice. The two reflux extracts are filtered, and the filtrates are combined and concentrated into an extract. The wet granulation method is used to add auxiliary materials at a material-auxiliary ratio of 1:1, and the granules are dried at a drying temperature of 60°C to obtain preparation granules, which are packaged into bags. The above amount is the amount for one bag.

[0089] Comparative Example 2

[0090] The difference from Comparative Example 1 is that the preparation method described in Example 4 is adopted for preparation, and the granule preparation is prepared according to the method of Example 9 and packaged into bags, and the above amount is the amount of one bag.

[0091] Comparative Example 3

[0092] The difference from Example 1 is that the amount of Astragalus is 15g, the amount of raw sun-dried ginseng is 5g, and the rest is the same as Example 1. The granular preparation is prepared by the method of Example 4 and Example 9, and packaged into bags. The above amount is the amount of one bag.

[0093] Comparative Example 4

[0094] The composition is the same as that in Example 1, and the preparation method is different from that in Example 4 in that the volume fraction of the ethanol solution used for reflux extraction of the mixture 1 is 60%, and the rest is the same as that in Example 4. After obtaining the composition, the granular preparation is prepared by the method of Example 9 and packaged into bags, and the above amount is the amount of one bag.

[0095] Comparative Example 5

[0096] The composition is the same as that of Example 1, and the difference between the preparation method and that of Example 4 is that when the mixture 2 is mixed with water for soaking and boiling, the boiling time is changed to 40 minutes, and the rest is the same as that of Example 4. After obtaining the composition, the granule preparation is prepared by the method of Example 9 and packaged into bags, and the above amount is the amount of one bag.

[0097] Comparative Example 6

[0098] The composition is the same as in Example 1, and the preparation method is different from that in Example 4 in that the two alcohol precipitation steps are not performed in the process of obtaining Extract 2, and the rest is the same as in Example 4. After obtaining the composition, the granule preparation is prepared by the method of Example 9 and packaged into bags, and the above amount is the amount of one bag.

[0099] Comparative Example 7

[0100] The composition is the same as in Example 1, and the difference between the preparation method and Example 4 is that no complex enzyme is added in the process of obtaining the reflux extract 2, and the rest is the same as in Example 4. After obtaining the composition, the granule preparation is prepared by the method of Example 9 and packaged into bags, and the above amount is the amount of one bag.

[0101] Comparative Example 8

[0102] The composition is the same as that in Example 1, and the difference between the preparation method and that in Example 4 is that in the process of obtaining the reflux extract 2, the weight ratio of cellulase to pectinase in the added complex enzyme is 2:1, and the rest is the same as that in Example 4. After obtaining the composition, the granular preparation is prepared by the method of Example 9 and packaged into bags, and the above amount is the amount of one bag.

[0103] Embodiment 14

[0104] A total of 180 patients with OSAHS who were treated in the Affiliated Hospital of Changchun University of Chinese Medicine from January 2022 to October 2023 were included. The inclusion criteria were as follows: they met the diagnostic criteria of the disease in the "Guidelines for the Diagnosis and Treatment of Obstructive Sleep Apnea-Hypopnea Syndrome (2011 Revised Edition)", and the severity of OS-AHS was divided into mild, moderate, and severe according to the guidelines. Mild: apnea-hypopnea index (AHI) 5-15 times / hour, oxygen saturation (SpO2) 85-90%; moderate: AHI 16-30 times / hour, SpO2 80-84%; severe: AHI>30 times / hour, SpO2<80%. According to the random number table method, the patients were divided into 9 groups, 20 cases in each group, and the number of mild, moderate and severe cases in each group was the same, respectively recorded as Example 9 group and Comparative Examples 1-8 group. The patients in Example 9 group took the granule preparation of Example 9 once a day, one bag at a time, and the patients in Comparative Examples 1-8 groups took the granule preparation of Comparative Examples 1-8, twice a day, one bag at a time. There was no statistically significant difference in gender, age, BMI, and disease severity among the 9 groups (P>0.05), and they were comparable. This study was approved by the Ethics Committee of the Affiliated Hospital of Changchun University of Chinese Medicine, and all subjects signed the "Informed Consent" before the experiment. The Epworth sleepiness score (ESS) was used to evaluate the daytime sleepiness of patients: 0-9 points = normal, 10-13 points = mild, 14-19 points = moderate, and 20-23 points = severe. The treatment lasted for 15 consecutive days. The daytime sleepiness of different groups before and after treatment was statistically analyzed using SPSS 26.0 software. Paired t-test was used for intra-group comparison and independent sample t-test was used for inter-group comparison. The results are shown in Table 1.

[0105] Table 1 Comparison of ESS scores in patients with obstructive sleep apnea-hypopnea syndrome in different groups

[0106] Group Before treatment (minutes) After treatment (minutes) Example 9 Group 16.52±3.21 9.42±2.11 Comparative Example 1 14.28±4.32 13.11±3.21 Comparative Example 2 15.31±2.42 12.12±2.02 Comparative Example 3 14.98±3.11 11.82±1.23 Comparative Example 4 15.61±2.78 11.68±1.42 Comparative Example 5 14.66±3.14 10.89±2.43 Comparative Example 6 15.01±2.02 12.02±1.13 Comparative Example 7 14.78±3.68 12.04±1.51 Comparative Example 8 15.58±2.57 11.65±2.32

[0107] It can be seen from Table 1 that the ESS scores of the nine groups before treatment were comparable and had little difference. After treatment, the treatment effect of the Example 9 group was the best, and the effects of the other groups were average.

[0108] Embodiment 15

[0109] Compare the effects of the granule preparation of Example 9 and the Shengyang Yiwei Decoction formula in the treatment of OSAHS (obstructive sleep apnea-hypopnea syndrome), wherein the Shengyang Yiwei Decoction formula consists of 30g of Astragalus, 15g of Pinellia, 15g of Ginseng, 15g of Radix Glycyrrhizae, 9g of Angelica dahurica, 9g of Saposhnikovia divaricata, 9g of White Peony Root, 9g of Notopterygium incisum, 6g of Tangerine Peel, 5g of Poria, 5g of Bupleurum, 5g of Alisma, 5g of Atractylodes, and 1.5g of Coptis chinensis.

[0110] (1) Effects on serum HIF-1α, IFN-γ and IL-4 levels in mice with intermittent hypoxia

[0111] Forty-eight 4-week-old male C57BL / 6J healthy mice (weighing 20-22 g) were adaptively fed under specific pathogen-free conditions for 3 days, and then randomly divided into four groups according to the research purpose, namely Group A (blank control group: normoxia), Group B (model group), Group C (model + Shengyang Yiwei Decoction control group), and Group D (model + Example 9 granule treatment group), with 12 mice in each group.

[0112] The mice in group A were placed in a normoxic environment (oxygen content concentration was 21%), and the mice in groups B, C, and D were placed in a closed oxygen chamber. The oxygen chamber switch was turned on, and the ratio of oxygen and nitrogen was adjusted to make the oxygen concentration in the chamber 10% for 8 hours. After that, the normoxic environment in the oxygen chamber was restored for 16 hours, and the model was continued for 4 weeks. Modeling success criteria: After 2 weeks, the hemoglobin content of each group was tested by ELISA. If there was a significant difference between group A and group B, C, and D, the model was considered to be successful. After 2 weeks of modeling, 0.2 mL of blood was collected from the orbital vein of the mice for testing the modeling results. The results are shown in Table 2.

[0113] Table 2 Changes in hemoglobin content in whole blood of mice in each group after 2 weeks of modeling (x±SD)

[0114]

[0115] Note: Compared with group A, *P<0.05, **P<0.01

[0116] Group A received no intervention. Group B was gavaged with 0.5 mL of distilled water once a day 2 weeks after modeling. Groups C and D were calculated based on the dosage conversion of experimental animals, and the daily dosage for mice in groups C and D was 2.73 g kg -1 According to this ratio, the formula of group C and group D was dissolved in distilled water for gavage once a day. Therapeutic gavage treatment was carried out simultaneously with modeling and lasted for 2 weeks.

[0117] Four weeks after modeling, no food was given after 8:00 p.m., and the animals in the four groups were weighed and recorded according to their serial numbers at 8:00 a.m. the next day. Sodium pentobarbital (50 mg kg -1 ) Intraperitoneal injection anesthesia, after successful anesthesia, blood was collected from the abdominal aorta, about 0.8 mL of blood was collected in a 1.5 mL centrifuge tube, and after being placed at room temperature for 3 h, the blood was centrifuged at 8000 r / min -1 Centrifuge for 10 min (centrifugal radius 6 cm), collect the upper serum, divide into 1.5 mL centrifuge tubes and store in -80℃ refrigerator for testing. ELISA kits were used to detect the levels of HIF-1α, IFN-γ and IL-4 in serum.

[0118] The levels of HIF-1α, IFN-γ, and IL-4 in the serum of mice in each group were as follows: Figure 1 As shown. Compared with group A, the HIF-1α concentration in the serum of mice in groups B, C, and D was significantly increased, further verifying the success of the model. Compared with group B, the HIF-1α, IFN-γ, and IL-4 concentrations in the serum of mice in groups C and D were significantly reduced, indicating that both have clinical significance in treating OSAHS by reducing the concentration levels of HIF-1α, IFN-γ, and IL-4. At the same time, the degree of reduction in the concentrations of HIF-1α, IFN-γ, and IL-4 in the serum of mice in group D was significantly higher than that in group C, indicating that the granule formula of the present invention has a better therapeutic effect than the traditional decoction formula.

[0119] (2) Effects on NF-κB expression in nasal mucosal tissue of mice with intermittent hypoxia

[0120] The modeling process and animal grouping were the same as described above (1).

[0121] After 4 weeks of modeling, no food was given after 8:00 p.m., and the four groups of animals were weighed and recorded at 8:00 a.m. the next day. They were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg / kg) and bled to death. Six mice were randomly selected from each of the A, B, C, and D groups. The line between the two ears of the mice was used as an incision, and the connective tissues such as fur and muscle on the head of the mice were peeled off with ophthalmic scissors until the nose was exposed. The mandible and teeth were removed with mouse bone scissors, and the entire nose was cut off together with the nasal septum, and placed in 4% paraformaldehyde at 4°C overnight. The remaining 6 mice in the A, B, C, and D groups were cut with the line between the two ears of the mice, and the connective tissues such as fur and muscle on the head of the mice were peeled off with ophthalmic scissors until the nasal septum was exposed. The nasal septum was cut off with ophthalmic scissors, and then the nasal septum mucosa was peeled off with tweezers and put into liquid nitrogen for quick freezing, and then transferred to a -80°C refrigerator for storage. The entire peeling process must be done carefully and slowly, and the nasal septum mucosa should not be scratched.

[0122] The mouse nasal mucosal tissue was taken, decalcified, dehydrated, trimmed, embedded, and sliced. It was dewaxed to water using xylene and gradient ethanol, and then antigen repair was performed. The slices were placed in 3% hydrogen peroxide at room temperature for 10 minutes; washed with PBS 3 times, 5 minutes each time, to block endogenous peroxidase, and the primary antibody was added after serum blocking, overnight at 4°C, and then washed with PBS 3 times, 5 minutes each time, and then the secondary antibody was added. After repeating the PBS wash 3 times, fresh DAB color development solution was prepared and added to the tissue. Color development was performed at room temperature. The color development time was controlled under a microscope. The positive color was brown-yellow. The slices were washed with distilled water to stop color development, and hematoxylin was used for counterstaining for 3 minutes. The slices were washed with tap water, and the blue was returned to clear water and then rinsed with running water. Finally, the slices were dehydrated with gradient ethanol, transparentized with xylene, and sealed with neutral gum. The microscopic camera system was used to collect images of the slices, and the Halo data analysis system was used to calculate the positive area ratio of each image (%DAB PositiveTissue). The results are shown in Figure 2 .

[0123] Take 10-20 mg of mouse nasal mucosal tissue and put it in a mortar to extract total RNA. Then prepare a reverse transcription reaction system for reverse transcription, add each reagent in turn, and place it on a PCR instrument for reaction. －△△CT The relative mRNA expression level of NF-κB in mouse nasal mucosa was calculated and purified by ULTRAPAGE. Figure 3 .

[0124] NF-κB exists in the cytoplasm. Generally, NF-κB is inactive and can be activated by upstream molecules. It plays a key regulatory role in multiple pathological and physiological processes such as immune response, inflammatory response, cell differentiation, proliferation, and apoptosis. Figure 2 , Figure 3 It can be seen that the protein content and relative expression of NF-κB in the model group were higher than those in the blank group, while the protein content and relative expression of NF-κB in the drug-treated group were lower than those in the model group, indicating that the drug-treated group was effective in regulating the expression of NF-κB. At the same time, the protein content and relative expression of NF-κB in group D were lower than those in group C, indicating that the granules of the present invention have a stronger inhibitory effect on NF-κB in the nasal mucosa than traditional decoctions, suggesting that the granules of the present invention have a better anti-inflammatory effect by inhibiting the expression of NF-κB in the nasal mucosa.

[0125] Example 16

[0126] Acute toxicity test of the particles described in Example 9

[0127] 40 SD rats were numbered and entered into an Excel table. The rats were randomly divided into groups using computer-generated random numbers, with 10 rats in each group, including a blank control group (distilled water), a low-dose group (1 g / kg), a medium-dose group (2.3 g / kg), and a high-dose group (4.6 g / kg) of the granules of Example 9. After fasting for 12 hours but not water, the rats were given a single oral administration of 0.2 ml / 10 g each time. The rats' general conditions (body weight, diet, fur, behavior, secretions, excretions, etc.) and poisoning and death were observed for 14 consecutive days. The rats' food intake and body weight changes were recorded before administration (day 0), on the 7th day, and on the 14th day after administration. For specific results, see Figure 4 , 5 .

[0128] Depend on Figure 4 , 5 It can be seen that compared with the blank group, the rats still reacted to external stimuli after administration, and no death occurred 14 days after administration, and the body weight gradually increased. There was no significant difference in food intake compared with the blank group. In addition, after observation, the rats in the granule group of the present invention had a normal appearance, no reduced activity, drowsiness, curling, loose hair, etc., and no abnormal secretions were found in the eyes, ears, mouth, and nose, indicating that the granules of the present invention had no obvious acute toxic reaction to rats.

[0129] Embodiment 17

[0130] Clinical study of the particles described in Example 9

[0131] Treatment plan

[0132] (1) Disease classification of the disease to be treated: Spleen Yang deficiency, phlegm and blood stasis blocking the collaterals

[0133] (2) TCM diagnosis: refer to the “Expert Consensus on TCM Diagnosis and Treatment of Snoring” (China Traditional Chinese Medicine Information Journal, 2019).

[0134] (3) Western medicine diagnosis: refer to the "Guidelines for the Diagnosis and Treatment of Obstructive Sleep Apnea-Hypopnea Syndrome (Primary Edition)" (2015).

[0135] (4) Reference standards for clinical cure or marked efficacy

[0136] Efficacy observation indicators:

[0137] Related symptoms: snoring during sleep, fatigue, spontaneous sweating, throat discomfort, heaviness of limbs, memory loss, stomach discomfort, frequent urination, unformed or sticky stools, pale tongue with slippery or greasy coating, tortuous veins at the bottom of the tongue, weak or slippery pulse. The main and secondary symptoms were assigned 0, 2, 4, 6 points and 0, 1, 2, 3 points respectively according to the symptoms of no, mild, moderate, and severe.

[0138] The efficacy standards refer to the "Guidelines for the Diagnosis and Treatment of Obstructive Sleep Apnea-Hypopnea Syndrome (Primary Edition)" (2015).

[0139] Symptom score reduction index = (pre-treatment score - post-treatment score) / pre-treatment score × 100%

[0140] Ineffective: no significant improvement in symptoms or signs, or even aggravation, and the syndrome score decreases by ≤30%;

[0141] Effective: symptoms and signs are significantly effective, and the syndrome score is reduced by >30% but ≤70%;

[0142] Markedly effective: symptoms and signs were significantly improved, with syndrome scores reduced by >70% but ≤95%;

[0143] Clinical cure: symptoms and signs disappear or almost disappear; symptom score decreases by >95%.

[0144] (5) Statistical analysis of clinical cases

[0145] Patients who visited the hospital from 2018 to 2022 were collected, and the patient information summary table is shown in Table 3. The patient information summary table mainly provides basic patient information, prescription changes, combined medication and concomitant medication, adverse reactions, follow-up visits (1 represents 1 follow-up visit, 2 represents 2 follow-up visits) or follow-up visits, etc. Each patient took the granules described in Example 9 once a day, one bag at a time, with a course of treatment of 7 days. The results show (Table 3) that the number of observed cases: 100 cases; 20 cured cases; 50 markedly effective cases; 22 effective cases; 8 ineffective cases, and the total effective rate was 92%. No adverse reactions were observed.

[0146] Table 3 Patient information table

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153] 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 principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A composition for treating obstructive sleep apnea-hypopnea syndrome, characterized in that: The composition is prepared from the following raw materials: 5-10g of Astragalus, 1-3g of Atractylodes macrocephala, 1-2g of dried orange peel, 3-8g of Cimicifuga heracleifolia, 3-6g of Bupleurum, 3-5g of Scutellaria baicalensis, 2-4g of raw sun-dried ginseng, 2-4g of roasted Licorice root, 1-4g of Mentha, 2-6g of Burdock fruit, 2-8g of Bombyx batryticatus, 2-4g of Periostracum cicadae, 1-4g of Ligusticum chuanxiong, 4-8g of Curcuma aromatica, 5-10g of Acorus calamus, 2-6g of Salvia miltiorrhiza, 2-5g of Pinellia ternata, 1-4g of Poria and 1-4g of White Peony Root; The preparation method of the composition comprises the following steps: mixing astragalus, atractylodes, dried orange peel and cimicifuga to obtain a mixture 1, mixing the mixture 1 with an ethanol solution with a volume fraction of 40% to 50% and performing reflux extraction to obtain a reflux extract 1; Mix bupleurum root, scutellaria root, sun-dried ginseng, roasted liquorice root and mint to obtain mixture 2, mix mixture 2 with water, soak, and then boil, keep boiling for 15min to 25min, filter and collect the filtrate as decoction liquid; Mix burdock seeds, silkworm, cicada shell, chuanxiong and turmeric to obtain mixture 3, mix mixture 3 with water, soak, then decoct, keep boiling for 30-40 minutes, filter, take the filtrate, add anhydrous ethanol to the concentration of ethanol solution is 50%-60%, filter to remove impurities, take the filtrate to recover ethanol, obtain extract 1, mix extract 1 with anhydrous ethanol to the concentration of ethanol solution is 80%-90%, filter to remove impurities, take the filtrate to recover ethanol, and obtain extract 2; A mixture 4 is obtained by mixing Acorus calamus, Salvia miltiorrhiza, Pinellia tuber, Poria cocos and Paeonia lactiflora, and the mixture 4 is mixed with water and a composite enzyme for enzymolysis, and the enzymolysis solution is heated and refluxed to obtain a reflux extract 2; the composite enzyme is composed of cellulase and pectinase; The reflux extract 1, the decoction, the extract 2 and the reflux extract 2 are mixed, concentrated into an extract, and dried and crushed to obtain the composition; The dosage of the complex enzyme is 0.06 g to 0.09 g of the complex enzyme per 1 g of the mixture 4, and the weight ratio of the cellulase to the pectinase is 1:2 to 3; The weight volume ratio of the mixture 1 to the ethanol solution with a volume fraction of 40% to 50% is 1 g: 8 to 12 mL; The soaking time is 20 to 30 minutes; The weight-to-volume ratio of the mixture 2 to water is 1 g: 5-8 mL, and the weight-to-volume ratio of the mixture 3 to water is 1 g: 7-10 mL; The temperature of the enzymolysis is 35° C. to 45° C., the time of the enzymolysis is 30 min to 50 min, and the pH value of the enzymolysis is 3.5 to 6.

5.

2. A granular preparation for treating obstructive sleep apnea-hypopnea syndrome, characterized in that: The granule preparation consists of the composition according to claim 1 and auxiliary materials.

3. The granular preparation according to claim 2, characterized in that The weight ratio of the composition according to claim 1 to the auxiliary materials is 1:1.5-3.

4. The method for preparing the granule preparation according to claim 2 or 3, characterized in that: The method comprises the following steps: mixing the composition according to claim 1 with auxiliary materials, and then performing dry granulation to obtain the granule preparation.

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