A traditional Chinese medicine composition for treating chronic rhinosinusitis in children and a compound preparation thereof

Abstract

The present application belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chronic rhinosinusitis in children, a compound preparation of the traditional Chinese medicine composition and application. The present application firstly provides an optimized traditional Chinese medicine formula, which takes Radix Saposhnikoviae, Magnolia flower and Xanthium fruit as monarch drugs, and the weight ratio of the monarch drugs is in the range of 1:6:1 to 1:2:1, which has a significant reducing effect on the expression level of inflammatory factors in chronic rhinosinusitis mice in vivo. Further, the present application provides a compound preparation of the traditional Chinese medicine formula for treating chronic rhinosinusitis in children combined with probiotics, and surprisingly finds that the compound preparation 2 has a more efficient and significant treatment effect than other compound preparations and the control group. The traditional Chinese medicine formula and the probiotics have a synergistic effect when combined in a weight ratio of 10:2. The present application has important significance in providing a preparation with the characteristics of no drug resistance, no side effect and fast effect for children with chronic rhinosinusitis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chronic rhinosinusitis in children, a compound preparation thereof and application. BACKGROUND

[0002] The incidence of chronic rhinosinusitis is mainly in children, and the causes of the disease are that children are congenitally immunocompromised, have poor resistance to diseases, are prone to catch cold, upper respiratory tract infection and acute infectious diseases, and are induced to develop rhinosinusitis. In addition, children are prone to develop secondary rhinosinusitis due to nasal foreign bodies and nasal trauma because of neglecting nasal hygiene.

[0003] If children suffer from chronic rhinosinusitis, they are prone to have symptoms such as listlessness, loss of appetite, headache and dizziness. Since children do not know how to blow their noses, the excretions often accumulate in the nasal cavity and sinuses, and even flow back to the pharynx, which causes tense nasal obstruction and open-mouth breathing, and further causes the development of the maxillofacial region to stop, and long-term open-mouth breathing can make the lips thick, the teeth protrude outward, the nasal bridge flat, the hard palate high arch, the teeth misaligned, and form a "rhinosinusitis face".

[0004] At present, single anti-inflammatory drugs or traditional Chinese medicine preparations are mostly used in the clinical treatment of chronic rhinosinusitis in children. However, chronic rhinosinusitis is prone to recurrence, and long-term use of anti-inflammatory drugs such as glucocorticoids and macrolide antibiotics can easily produce drug resistance and adverse reactions, and has a great impact on the growth and development of children. The traditional Chinese medicine preparations such as the rhinosinusitis oral liquid on the market have a slow onset time and a long treatment cycle, resulting in poor treatment effect. Therefore, there is an increasing urgent need for preparations with the characteristics of no drug resistance, no side effects and fast onset for patients with chronic rhinosinusitis.

[0005] Probiotics are bacteria that are beneficial to the human body, have important effects such as maintaining the balance of intestinal flora, enhancing the function of the immune system, and inhibiting the growth of harmful microorganisms, and among them, bifidobacterium and lactic acid bacteria are the two most widely used probiotics. With the continuous deepening of modern medical research, more and more attention is paid to the role of the intestinal-lung axis in various diseases, and it is noticed in the clinic that intestinal flora disorder can also be reflected in the respiratory tract, thereby causing the onset of respiratory diseases. Therefore, there are potential benefits in using probiotics to regulate the intestinal microenvironment to treat chronic rhinosinusitis in children. SUMMARY

[0006] The present application aims to provide a traditional Chinese medicine composition for treating chronic rhinosinusitis in children and a compound preparation thereof. The present application first provides an optimally adjusted traditional Chinese medicine composition, which has excellent effects in treating chronic rhinosinusitis in children.

[0007] In another aspect, the present application further provides a combined preparation of a traditional Chinese medicine composition and probiotics for treating chronic rhinosinusitis in children, and surprisingly finds that the traditional Chinese medicine composition and probiotics have a synergistic effect when used in a proper dosage range, which is of great significance in providing a preparation with no drug resistance, side effects and fast effect for patients with chronic rhinosinusitis in children.

[0008] In the traditional Chinese medicine composition of the present application, the Radix Saposhnikoviae, Magnolia flower and Semen Xanthii are used as monarch drugs, the Cortex Mori and Rhizoma Acori are used as ministerial drugs, the Retinervus Luffae Fructus, Cortex Lycii and Radix Glycyrrhizae are used as auxiliary drugs, and the Herba Rubi Adenicola, Beeswax and Radix Glycyrrhizae are used as ministerial drugs.

[0009] Specifically, the present application first provides a traditional Chinese medicine composition for treating chronic rhinosinusitis in children, which is composed of the Radix Saposhnikoviae 5-20, Magnolia flower 20-60, Semen Xanthii 5-20, Cortex Mori 5-20, Rhizoma Acori 5-20, Retinervus Luffae Fructus 5-20, Cortex Lycii 5-20, Herba Rubi Adenicola 5-20, Beeswax 2-10 and Radix Glycyrrhizae 2-10 in terms of weight.

[0010] Preferably, the traditional Chinese medicine composition is composed of the Radix Saposhnikoviae 5-15, Magnolia flower 30-50, Semen Xanthii 5-15, Cortex Mori 5-15, Rhizoma Acori 5-15, Retinervus Luffae Fructus 5-15, Cortex Lycii 5-15, Herba Rubi Adenicola 5-15, Beeswax 2-10 and Radix Glycyrrhizae 2-10 in terms of weight.

[0011]

[0012] More preferably, the traditional Chinese medicine composition is composed of the Radix Saposhnikoviae 10, Magnolia flower 40, Semen Xanthii 10, Cortex Mori 10, Rhizoma Acori 10, Retinervus Luffae Fructus 10, Cortex Lycii 10, Herba Rubi Adenicola 10, Beeswax 5 and Radix Glycyrrhizae 5 in terms of weight.

[0013] Further, the traditional Chinese medicine composition in the present application can be used together with a pharmaceutical carrier to prepare pills, powders, granules, capsules and clear paste.

[0014] The present application also provides a preparation method of the traditional Chinese medicine composition for treating chronic rhinosinusitis in children, and the steps include:

[0015] 1) The medicinal materials are weighed, washed, dried, cut, processed, pulverized and passed through a fine sieve;

[0016] 2) The corresponding powders are weighed according to the above weight ratio, soaked in distilled water for 2-3 h, and then heated to 90-100℃ by using a constant temperature heating instrument, and the medicinal materials are decocted for 2-3 times, 5-10 times of the total weight of all original medicinal materials are added each time, the decocting time is 3-4 h, the supernatant is taken after the filtrate is combined and precipitated, and the supernatant is further concentrated into a paste by using a rotary evaporator, and the paste powder is obtained after spray drying, and the corresponding traditional Chinese medicine pills are prepared according to the conventional process.

[0017] ​In another aspect, the present application further provides a compound preparation comprising the traditional Chinese medicine composition of any of the preceding aspects in combination with probiotics.

[0018] In particular, the present application further provides a compound preparation for treating chronic rhinosinusitis in children, comprising 100-300 parts by weight of the powder obtained by grinding any of the traditional Chinese medicine pills prepared by the above method, and 10-40 parts by weight of probiotic powder.

[0019] Preferably, the compound preparation comprises 100 parts by weight of the powder obtained by grinding any of the traditional Chinese medicine pills prepared by the above method, and 10-20 parts by weight of probiotic powder.

[0020] More preferably, the compound preparation comprises 100 parts by weight of the powder obtained by grinding any of the traditional Chinese medicine pills prepared by the above method, and 20 parts by weight of probiotic powder.

[0021] Preferably, the probiotics are one or more of Bifidobacterium and Lactobacillus.

[0022] Preferably, the probiotics are Bifidobacterium.

[0023] Preferably, the active content of Bifidobacterium in the probiotic powder is 1.0 x 10 7 -5.0 x 10 7 CFU.

[0024] More preferably, the active content of Bifidobacterium in the probiotic powder is 2.0 x 10 7 CFU.

[0025] The present application also provides a preparation method for the compound preparation of the traditional Chinese medicine composition in combination with probiotics for treating chronic rhinosinusitis in children, comprising the following steps:

[0026] 1) Preparing: grinding any of the prepared traditional Chinese medicine pills into powder, and passing through a 200-mesh sieve for use;

[0027] 2) Mixing: adding the above powder into a batch mixer, and adding probiotic powder, and mixing in a mixing machine for 30 minutes;

[0028] 3) Filling capsules: filling the compound powder after step 2) into a capsule shell under nitrogen filling conditions to obtain a capsule compound preparation, and storing at 2-8°C.

[0029] The present application provides the use of the compound preparation of the traditional Chinese medicine composition in combination with probiotics as described above in the preparation of a pharmaceutical preparation for treating chronic rhinosinusitis in children.

[0030] Preferably, the pharmaceutical preparation is one or more of capsules, tablets, and pastes.

[0031] In the present application, the pharmacological basis of the traditional Chinese medicine composition is that:

[0032] Wind-preventing: pungent, sweet, slightly warm, enters bladder, liver and spleen channels; Shennong's Classic of Materia Meda states that wind-preventing "mainly treats dizziness and headache, aversion to wind, wind evil, blindness, and pain in bones and joints", and it can dispel wind and cold, relieve exterior syndrome, stop pain and reduce swelling.

[0033] Magnolia flower: pungent, slightly warm, enters lung and stomach channels; Shennong's Classic of Materia Meda states that magnolia flower "mainly treats fever of five zang organs, headache and brain pain", and it can dispel wind and dampness, resolve toxin and reduce swelling, remove blood stasis and relieve pain.

[0034] Xanthium fruit: pungent, bitter, warm, returns to lung channel; Shennong's Classic of Materia Meda states that it "mainly treats headache and cold, arthralgia, pain in limbs, and aversion to meat", and it can unblock nose, dispel wind, regulate qi and blood, and relieve pain.

[0035] White mulberry bark: sweet and cold, returns to lung and spleen channels; Shennong's Classic of Materia Meda states that it "mainly treats injury, five kinds of exhaustion, collapse, pulse collapse, and deficiency of qi", and it can clear lung and relieve asthma, remove water and reduce swelling, activate blood and remove blood stasis, resolve phlegm and relieve cough, and produce saliva and relieve thirst.

[0036] Acorus: pungent, slightly warm, enters lung, liver and spleen channels; Shennong's Classic of Materia Meda states that it "mainly treats wind, cold and dampness, cough and upward flow of qi, and it can open heart orifice, supplement five zang organs, open nine orifices, brighten eyes and ears, and restore voice", and it can dispel wind and dampness, open orifices and resolve phlegm, regulate qi and activate blood.

[0037] Luffa: sweet, flat, returns to lung, stomach and liver channels; Shennong's Classic of Materia Meda states that it "unblocks meridians, harmonizes blood and vessels, and resolves phlegm and regulates qi", and it can unblock meridians, remove toxin and reduce swelling, cool blood and remove blood.

[0038] Radix Lycii: sweet, cold, returns to lung, liver and kidney channels; Shennong's Classic of Materia Meda states that it "mainly treats five kinds of evil qi, heat in the center, and thirst", and it can clear heat and cool blood, clear lung and reduce fire.

[0039] Orpiment: bitter, flat, returns to liver and kidney channels; Shangmu Shiyi states that it "dispels miasma, treats measles, brightens eyes, removes dampness, relaxes and unblocks meridians and joints, and treats pain in limbs, hands and feet, and waist", and it can dispel wind and unblock meridians, benefit water and unblock channels.

[0040] Beehive: sweet and salty, flat, returns to liver and stomach channels; Shennong's Classic of Materia Meda states that it "mainly treats convulsions, epilepsy, ulcer, cold and heat evil, and intestinal hemorrhoids", and it can remove toxin and resolve nodes, dispel wind and relieve pain, benefit kidney and warm yang, and kill insects and relieve itching.

[0041] Gancao: sweet, flat, returns to heart, lung, spleen and stomach channels; Shennong's Classic of Materia Meda states that it "mainly treats cold and heat evil of five zang organs and six fu organs, strengthens bones and muscles, increases muscle, and relieves pain of gold and ulcer", and it can supplement spleen and qi, clear heat and resolve toxin, remove phlegm and relieve cough.

[0042] The embodiments of the present application have at least the following beneficial effects:

[0043] The present inventors have conducted research and first provided an optimally adjusted traditional Chinese medicine composition which has excellent effects of treating chronic rhinosinusitis in children. In the compatibility of the monarch drug in the composition, the radix saposhnikoviae, magnolia flower and xanthium fruit belong to an excellent monarch drug compatibility system, the ministerial drugs are mulberry bark, kudzu vine bark, rhizoma alocasia, and liriodendron; the auxiliary drugs are lagenaria and honeycomb. This compatibility can exert the maximum efficacy and synergistic effect of each traditional Chinese medicine, and the therapeutic effect of the traditional Chinese medicine composition of the present application is also significantly better than that of the similar formula in the prior art. In the present application, the monarch drug is pungent and warm, and can relieve the exterior, dredge the collaterals and open the orifices; the ministerial drug can drain the lung, clear heat and eliminate dampness; the auxiliary drug can dispel wind and dredge the collaterals; and the overall treatment effect is to promote the lung, eliminate dampness and open the orifices.

[0044] In the composition, the radix saposhnikoviae, magnolia flower and xanthium fruit are used as the monarch drug, and the weight ratio of the monarch drug compatibility is in the range of 1:6:1 to 1:2:1, which can significantly reduce the expression level of inflammatory factors in the body of chronic rhinosinusitis mice, and it is found that the treatment effect of the composition 3 group is the best, and the data show that it has a significant synergistic protective effect on the damage of the nasal mucosa.

[0045] Further, a compound preparation of the traditional Chinese medicine composition for treating chronic rhinosinusitis in children combined with probiotics is further provided, and it is surprisingly found that the compound preparation 2 has a more efficient and significant treatment effect than other compound preparations and the control group, the cure rate is 80%, and the effective rate is as high as 100%. The traditional Chinese medicine composition and the probiotics have a synergistic effect when they are combined in a weight ratio of 10:2, and the Q value is 1.25, and Q>1.15. The present research has important significance for providing a preparation with the characteristics of no drug resistance, no side effect and fast effect for children with chronic rhinosinusitis. BRIEF DESCRIPTION OF DRAWINGS

[0046] Figure 1 : HE staining diagram of the traditional Chinese medicine composition for treating chronic rhinosinusitis in children in each group

[0047] Figure 2 : Q value of the compound preparation of the traditional Chinese medicine composition combined with probiotics in different weight ratios DETAILED DESCRIPTION

[0048] The present application aims to provide a traditional Chinese medicine composition for treating chronic rhinosinusitis in children, a compound preparation thereof, a preparation method thereof and an application thereof. The following will be specifically described in combination with the content of the experimental examples, but the scope of the present application is not limited.

[0049] The medicinal materials, excipients, reagents or instruments used in the embodiments of the present application are not marked with the manufacturer, and are all conventional products that can be obtained from the market. The medicinal materials used meet the provisions of the inspection items of each medicinal material in the first part of Chinese Pharmacopoeia, and the excipients meet the use standards in the fourth part of Chinese Pharmacopoeia.

[0050] 1. Screening test of suitable weight ratio of monarch drug

[0051] Example 1.1 A traditional Chinese medicine composition for treating chronic rhinosinusitis in children

[0052] A traditional Chinese medicine composition for treating chronic rhinosinusitis in children, wherein the weight parts of Qianfeng, Xinyihua and Cang'ersi are 1:6:1, and the composition is composed of Qianfeng 10, Xinyihua 60, Cang'ersi 10, Sangbaipi 10, Shichangpu 10, Ciqueluo 10, Digupi 10, Lulutong 10, Fengfang 5, and Gancao 5. The preparation steps include:

[0053] 1) Weigh the medicinal materials, wash, dry, cut, process, crush, and pass through a fine sieve;

[0054] 2) Weigh the corresponding powder according to the above weight ratio, soak in distilled water for 2-3 h, then heat to 90-100°C using a constant temperature heating instrument, repeat the decoction of the medicinal materials 2-3 times, each time adding 5-10 times the total weight of the original medicinal materials, decoct for 3-4 h, take the supernatant after standing and combining the filtrate, and further concentrate the supernatant into a paste using a rotary evaporator, spray dry to obtain a paste powder, and prepare a corresponding traditional Chinese medicine pill 1 according to the conventional process.

[0055] Example 1.2 A traditional Chinese medicine composition for treating chronic rhinosinusitis in children

[0056] A traditional Chinese medicine composition for treating chronic rhinosinusitis in children, wherein the weight parts of Qianfeng, Xinyihua and Cang'ersi are 1:4:1, and the composition is composed of Qianfeng 10, Xinyihua 40, Cang'ersi 10, Sangbaipi 10, Shichangpu 10, Ciqueluo 10, Digupi 10, Lulutong 10, Fengfang 5, and Gancao 5. Prepare a traditional Chinese medicine pill 2 according to the aforementioned preparation method.

[0057] Example 1.3 A traditional Chinese medicine composition for treating chronic rhinosinusitis in children

[0058] A traditional Chinese medicine composition for treating chronic rhinosinusitis in children, wherein the weight parts of Qianfeng, Xinyihua and Cang'ersi are 1:2:1, and the composition is composed of Qianfeng 10, Xinyihua 20, Cang'ersi 10, Sangbaipi 10, Shichangpu 10, Ciqueluo 10, Digupi 10, Lulutong 10, Fengfang 5, and Gancao 5. Prepare a traditional Chinese medicine pill 3 according to the aforementioned preparation method.

[0059] Example 1.4 A traditional Chinese medicine composition for treating chronic rhinosinusitis in children

[0060] A traditional Chinese medicine composition for treating chronic rhinosinusitis in children, wherein the main drugs are Qianhu, Xinyihua and Cang'erzi (weight ratio: 1:1:1), and the composition is composed of Qianhu 10, Xinyihua 10, Cang'erzi 10, Sangbaipi 10, Shichangpu 10, Ciqueluo 10, Digupi 10, Lulutong 10, Fengfang 5, and Gancao 5. The traditional Chinese medicine pills 4 are prepared according to the preparation method described above.

[0061] Comparative Example 1.5: A traditional Chinese medicine composition for treating chronic rhinitis or allergic rhinitis is disclosed in the prior art (Cai Xiling. Cleverly use Ephedra to treat chronic diseases [J]. Chinese community doctors (medical professionals), 2012, 14 (17): 229.), wherein the traditional Chinese medicine components for treating chronic rhinitis or allergic rhinitis are Xinyihua 10g, Cang'erzi 10g, Qianhu 10-15g, and Lulutong 10-30g. Based on the composition disclosed in the literature, Xinyihua 10, Cang'erzi 10, Qianhu 10, and Lulutong 10 are taken by weight, and the traditional Chinese medicine comparative pill 1 is prepared according to the preparation method described above.

[0062] Comparative Example 1.6: In order to explore the effect of Qianhu, Xinyihua and Cang'erzi as the main drugs, further, the Qianhu is removed in Example 1, and only Xinyihua and Cang'erzi are used as the main drugs to obtain a traditional Chinese medicine composition for treating chronic rhinosinusitis in children, which is as follows: Xinyihua and Cang'erzi are the main drugs (weight ratio: 6:1), and the composition is composed of Xinyihua 60, Cang'erzi 10, Sangbaipi 10, Shichangpu 10, Ciqueluo 10, Digupi 10, Lulutong 10, Fengfang 5, and Gancao 5. The traditional Chinese medicine comparative pill 2 is prepared according to the preparation method described above.

[0063] Example 1.7: Effect test of traditional Chinese medicine compositions 1-4 and comparative groups 1-2 in treating chronic rhinosinusitis in children

[0064] 28 C57BL / 6J mice (purchased from the Experimental Animal Center of Sun Yat-sen University, randomly divided into 7 groups according to weight, 4 mice in each group), the average weight of which is 20±2g, are placed in a closed box with a temperature of 25-26℃ and a humidity of 70% for adaptive feeding, and the experiment is carried out after 10 days. Randomly divide the 28 mice into a model group, a composition 1 group, a composition 2 group, a composition 3 group, a composition 4 group, a comparison group 1, and a comparison group 2. After the mice are anesthetized, a surgical knife is used to cut a cut of about 2mm horizontally in the middle of the back of the mouse nose, the subcutaneous fat and other tissues are separated to expose the sinus cavity to the outside, and immediately a small hole with a diameter of about 0.5mm is picked out at the opening of the two sides of the maxillary sinus with a knife tip, and a prepared 10μl 3 type of capsular pneumococcus (ATCC49619 pneumococcus strain: purchased from Shanghai Sangon) bacterial solution is transplanted into the sinus cavity, and finally the skin is sutured with a needle and thread, and the tissue fluid is wiped with alcohol, that is, a chronic rhinosinusitis mouse model is made. Two weeks after the modeling is successful, the composition 1 group, the composition 2 group, the composition 3 group, the composition 4 group, the comparison group 1, and the comparison group 2 are all treated by gavage with a dosage of 5g / kg, and the model group is gavaged with an equal amount of normal saline. The administration frequency is 3 times / day, and the administration is continuously given for 3 weeks, and the performance symptoms of the mice in each group are observed.

[0065] Peripheral blood inflammatory factor level: 12h after the last administration, 1ml of aortic blood of the mice in each group is collected. After the blood is left to stand for 0.5h, it is centrifuged in a centrifuge at 4000r / min for 15min, the upper serum is collected with a sterile pipette, and then the expression levels of TNF-α and IL-6 inflammatory factors in the peripheral blood of the mice are determined by ELISA, and the results are shown in Table 1.

[0066] Sinus mucosa histopathology: after 3 weeks of administration, the mice are sacrificed, the corresponding sinus mucosa tissues are taken out on the clean bench, fixed with 4% paraformaldehyde solution, and the sinus mucosa is made into a section by HE staining, and the histopathological changes of the sinus mucosa are observed under a light microscope, and the HE staining section is shown in Figure 1 .

[0067] Table 1: Expression levels of TNF-α and IL-6 inflammatory factors in the peripheral blood of mice

[0068]

[0069] Results: In terms of general mouse state, before modeling, the 7 groups of mice were normal diet, good mental state, normal activity, and lustrous fur, without symptoms of chronic rhinosinusitis such as nasal congestion, rhinorrhea, and sneezing. After 2 days of modeling, the mice all had severe symptoms of rhinorrhea, scratching nose, and sneezing. After administration, the model group mice still had severe symptoms of rhinorrhea, scratching nose, and sneezing, and the administration groups 1-4 and the comparative groups 1-2 all had different degrees of alleviation, among which the mice in the administration groups 1 and 3 had milder symptoms than those in the administration groups 2 and 4, and the administration groups 1-4 had superior improvement of symptoms to the comparative groups 1-2.

[0070] As shown in Table 1, the levels of TNF-α and IL-6 in the peripheral blood of the model group mice were high, while the levels of inflammatory factors in the administration groups 1-4 were lower than those in the model group, among which the differences in the administration groups 1-3 had significant statistical significance (P<0.05), and the administration groups 1-4 also had significant statistical significance in the reduction of inflammatory factors compared with the comparative groups 1-2 (P<0.05). As shown in the results, among the monarch drug combinations, Fangfeng, Xinyihua, and Cang'erzi belong to an excellent monarch drug combination system, and the organic combination mode can exert the maximum efficacy and synergistic effect of each traditional Chinese medicine, and the therapeutic effect of the traditional Chinese medicine composition of the application is also significantly superior to that of the related compositions in the prior art.

[0071] In addition, the applicant also found that, in the traditional Chinese medicine composition for treating chronic rhinosinusitis in children, when Fangfeng, Xinyihua, and Cang'erzi are used as the monarch drug, the weight ratio of the monarch drug combination has different effects on the expression level of inflammatory factors. Among them, the weight ratio of the monarch drug combination in the range of 1:6:1-1:2:1 has a significant reducing effect on the expression level of inflammatory factors in the mice with chronic rhinosinusitis, and it is also found that, with the increase of the weight ratio of Xinyihua in the monarch drug, the effect does not present a simple dose-dependent manner. The composition 3 group (weight ratio: 1:2:1) has a significant reducing effect on the expression level of inflammatory factors than the composition 4 group (weight ratio: 1:1:1), but the increase of the weight ratio of Xinyihua in the monarch drug does not present a dose-dependent effect of the compositions 1-2, and the therapeutic effect of the composition 1-2 is relatively poor compared with that of the composition 3 group. It can be seen that, in the traditional Chinese medicine composition, the weight ratio range of the monarch drug combination has a significant effect on the overall therapeutic effect.

[0072] In addition, from Table 1, Figure 1The HE staining results can know that the nasal mucosa of the model group showed more serious chronic inflammation, the distribution of the mucosal epithelial cells was uneven, there were a large number of epithelial cell necrosis, exfoliation, fibrous tissue hyperplasia and other symptoms, and there was obvious inflammatory cell infiltration. The compositions 1-4, the comparative group all have different degrees of improvement or alleviation, especially the composition 3 group, the improvement degree is obviously better than other compositions and the comparative group. After the administration treatment, the epithelial cells are clear and neat, and there is no obvious submucosal inflammatory cell infiltration and no gland hyperplasia phenomenon, the results show that it has a significant synergistic protective effect on the nasal sinus mucosa damage.

[0073] According to the above results and considering the cost of medication, the subsequent test uses composition 3 combined with probiotics to explore the preparation of more efficient composite preparations.

[0074] 2. High-efficiency composite preparation exploration test of composition 3 combined with probiotics

[0075] Example 2.1. Composite preparation 1 of traditional Chinese medicine composition combined with probiotics for treating children's chronic sinusitis

[0076] A composite preparation for treating children's chronic sinusitis, which is composed of a traditional Chinese medicine composition part and a probiotic part, wherein the traditional Chinese medicine composition part: 100 of the powder of traditional Chinese medicine pill composition 3 by weight; the probiotic part: 10 of the bifidobacterium powder with an active content of 2.0 x 10 7 CFU by weight, the preparation steps comprising: 1) pre-preparation: grinding the prepared traditional Chinese medicine pill composition 3 into powder, and passing through a 200-mesh sieve for use;

[0077] 2) mixing: adding the above powder into a batch mixer, and adding bifidobacterium powder, and mixing in the mixing machine for 30 minutes;

[0078] 3) capsule filling: filling the mixed composite powder of step 2) into a capsule shell under nitrogen filling conditions to obtain capsule composite preparation 1, and storing it at 2-8℃.

[0079] Example 2.2. Composite preparation 2 of traditional Chinese medicine composition combined with probiotics for treating children's chronic sinusitis

[0080] A composite preparation for treating children's chronic sinusitis, which is composed of a traditional Chinese medicine composition part and a probiotic part, wherein the traditional Chinese medicine composition part: 100 of the powder of traditional Chinese medicine pill composition 3 by weight; the probiotic part: 20 of the bifidobacterium powder with an active content of 2.0 x 10 7 CFU by weight, the composite preparation 2 is prepared according to the above preparation method.

[0081] Example 2.3 Compound preparation 3 of traditional Chinese medicine composition combined with probiotics for treating chronic rhinosinusitis in children

[0082] A compound preparation of traditional Chinese medicine composition combined with probiotics for treating chronic rhinosinusitis in children, which is composed of a traditional Chinese medicine composition part and a probiotic part, wherein the traditional Chinese medicine composition part: 100 of the powder of traditional Chinese medicine pill composition 3 counted by weight parts; the probiotic part: 30 of the Bifidobacterium powder with an active content of 2.0 x 10 7 CFU, prepared according to the preparation method described above to obtain compound preparation 3.

[0083] Example 2.4 Compound preparation 4 of traditional Chinese medicine composition combined with probiotics for treating chronic rhinosinusitis in children

[0084] A compound preparation of traditional Chinese medicine composition combined with probiotics for treating chronic rhinosinusitis in children, which is composed of a traditional Chinese medicine composition part and a probiotic part, wherein the traditional Chinese medicine composition part: 100 of the powder of traditional Chinese medicine pill composition 3 counted by weight parts; the probiotic part: 40 of the Bifidobacterium powder with an active content of 2.0 x 10 7 CFU, prepared according to the preparation method described above to obtain compound preparation 4.

[0085] Example 2.5 Control group 1: Traditional Chinese medicine composition for treating chronic rhinosinusitis in children:

[0086] A traditional Chinese medicine composition for treating chronic rhinosinusitis in children, which is only composed of traditional Chinese medicine, 100 of the powder of the traditional Chinese medicine composition 3 counted by weight parts, which is prepared by loading into a capsule shell according to the preparation method described above to obtain control group 1.

[0087] Example 2.6 Control group 2: Bifidobacterium powder:

[0088] A Bifidobacterium powder, which is composed of 20 of the Bifidobacterium powder with an active content of 2.0 x 10 7 CFU counted by weight parts, which is prepared by loading into a capsule shell according to the preparation method described above to obtain control group 2.

[0089] Example 2.7 Effect test of compound preparations 1-4 for treating chronic rhinosinusitis in children

[0090] Case source: Patients with chronic rhinosinusitis treated in the outpatient and inpatient departments of the Affiliated Hospital of Guangzhou Medical University from January 2023 to June 2023 were selected as research objects.

[0091] Inclusion criteria:

[0092] 1) Diagnosed as chronic rhinosinusitis, in line with the diagnostic criteria for chronic rhinosinusitis in the "Guidelines for the Diagnosis and Treatment of Chronic Rhinosinusitis".

[0093] 2) Age not more than 14 years, no heart, liver, kidney, brain and other diseases

[0094] 3) With the consent of the patient's parents and signed informed consent

[0095] 4) No related drug treatment in the past week.

[0096] Exclusion criteria:

[0097] 1) Do not meet the inclusion criteria and diagnostic criteria;

[0098] 2) Age greater than 14 years;

[0099] 3) Patients with liver, kidney, heart, blood system and other serious systemic diseases, mental illness;

[0100] 4) Allergic constitution or allergic to the components of the drugs in this trial, or unable to cooperate with treatment.

[0101] Experimental method: 60 cases of chronic pediatric sinusitis patients as the research object, randomly divided into 6 groups. Compound preparation treatment group 1-4, control group 1-2 are 10 cases, male and female 5 cases, age not more than 14 years old. All patients after entering the group are treated for 4 weeks.

[0102] Efficacy: Chronic sinusitis patients after treatment, clinical symptoms and signs disappeared, CT examination of the sinus cavity showed normal, symptom score decreased ≥95%, was cured; Chronic sinusitis patients after treatment, clinical symptoms and signs were improved, CT examination of the sinus cavity showed basically normal, symptom score decreased 70%-95%, was markedly effective; Chronic sinusitis patients after treatment, clinical symptoms and signs were improved, CT examination of the sinus cavity showed some improvement, symptom score decreased 30%-70%, was effective; Not up to the above standard, was invalid. Results are shown in Table 2.

[0103] Patient peripheral blood inflammatory factor level: After the last administration, the patient fasted for 12 hours, and the next morning, 5ml of venous blood was drawn from the arm. After centrifugation, the serum was separated, and the expression levels of TNF-α and IL-6 inflammatory factors in peripheral blood were detected by automatic biochemical analyzer. The results are shown in Table 3.

[0104] Table 2 Comparison of clinical efficacy of compound preparation treatment group and control group

[0105]

[0106]

[0107] Table 3: Expression levels of TNF-α and IL-6 inflammatory factors in peripheral blood of patients

[0108]

[0109] Results: From the comparison data of clinical curative effects of the treatment group and the control group in Table 2, the recovery rate and the effective rate of the compound preparation 1-4 (the weight ratio of the composition 3 powder to the Bifidobacterium powder is 10:1-10:4) combined with probiotics and the control group 1 (the composition 3 powder) and the control group (the Bifidobacterium powder) are significantly improved, which has significant statistical significance (*P<0.05), and it can be seen that the Chinese medicine composition combined with probiotics has a significant treatment effect on children with chronic sinusitis. Further, in the compound preparation 1-4, the treatment effect of the compound preparation 2 with a weight ratio of 10:2 is more efficient than that of other compound preparations, the recovery rate is 80%, and the effective rate is as high as 100%. And also, the expression level data of the peripheral blood TNF-α and IL-6 inflammatory factors in Table 3 further verify that the Chinese medicine composition combined with probiotics has a synergistic effect on the treatment of children with chronic sinusitis, and the compound preparation 2 can reduce the TNF-α level to about 10.63±1.98 ng / L and the IL-6 level to about 14.16±1.78, which has extremely significant statistical significance (**P<0.01).

[0110] And further, we use the King's formula to evaluate the treatment effect of the weight ratio of the composition 3 powder to the Bifidobacterium powder in the range of 10:1-10:4, and the conventional King's formula provides that Q<0.85 has an antagonistic effect, 0.85≤Q≤1.15 has an additive effect, and Q>1.15 has a synergistic effect. The calculation results are as follows Figure 2 .

[0111] Figure 2 The results show that when the weight ratio of the composition 3 powder to the Bifidobacterium powder is 10:1, the Q value is 0.92, indicating that it has a certain additive effect, when the weight ratio of the composition 3 powder to the Bifidobacterium powder is 10:2, the Q value is 1.25, and Q>1.15, indicating that it has a synergistic effect, and when the weight ratio of the composition 3 powder to the Bifidobacterium powder is 10:3-4, the Q values are 1.1 and 0.96 respectively. It can be seen that the compound preparation 2 is the optimal weight ratio, which can maximize the efficacy of the drug under the condition of cost saving.

[0112] The protection scope of the present application is not limited to the above-mentioned embodiments. The equivalent substitutions or transformations made by the skilled in the art on the basis of the present application are within the protection scope of the present application. The protection scope of the present application is subject to the claims.

Claims

1. A traditional Chinese medicine composition for treating chronic rhinosinusitis, characterized in that, By weight count, by Fang Feng 10, 20-60 Magnolia flowers, 10, 10, 10, 10, 10, 10, 10, 10, 5, 5 weight parts of Radix et Rhizoma Ginseng.

2. The traditional Chinese medicine composition of claim 1, wherein, By weight count, by Fang Feng 10, 40 Magnolia flowers, 10, 10, 10, 10, 10, 10, 10, 10, 5, 5 weight parts of Radix et Rhizoma Ginseng.

3. The preparation prepared from the traditional Chinese medicine composition according to any one of claims 1-2, characterized in that, The preparation consists of the traditional Chinese medicine composition according to any one of claims 1-2 and a pharmaceutically acceptable carrier thereof.

4. The preparation prepared from the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The preparation is a pill, a capsule, a clear paste, a granule.

5. The preparation method of the traditional Chinese medicine composition according to any one of claims 1-4, comprising the steps of: 1) weighing the medicinal materials, washing, drying, cutting, grinding, and passing through a fine sieve; 2) weighing the corresponding powder according to the above weight ratio, soaking in distilled water for 2-3 h, then heating to 90-100℃ with a constant temperature heating instrument, repeating the decoction of medicinal materials 2-3 times, adding 5-10 times the total weight of all original medicinal materials each time, decocting for 3-4 h, taking the supernatant after standing and combining the filtrate, further concentrating the supernatant into a paste using a rotary evaporator, spray drying to obtain a paste powder, and preparing the corresponding traditional Chinese medicine preparation according to the conventional process.

6. A compound preparation of a traditional Chinese medicine composition combined with probiotics for treating chronic rhinosinusitis, characterized in that, By weight, the powder 100 of traditional Chinese medicine prepared by the method of claim 5, 20 parts by weight of probiotic powder; the probiotic powder is a powder of bifidobacterium with an active content of 2.0 x 10 7 CFU. CFU of bifidobacterium.

7. The preparation method of the composite preparation according to claim 6, comprising the steps of: 1) pre-preparation: grinding any prepared traditional Chinese medicine preparation into powder, passing through a 200 mesh sieve for use; 2) mixing: adding the powder into a mixing machine and adding bacteria powder, mixing in the mixing machine for 30 minutes; 3) capsule filling: filling the mixed powder of step 2) into a capsule shell under nitrogen filling conditions to obtain a capsule composite preparation, and storing at 2-8℃.

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