CN118750549A - A Chinese medicine composition for treating chronic sinusitis in children and its compound preparation - Google Patents

Abstract

The present invention belongs to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating chronic sinusitis in children, and its composite preparation and application. The present invention first provides an optimized and adjusted traditional Chinese medicine formula, which uses siler, magnolia flower, and Xanthium sibiricum as the main medicine, and the weight ratio of the main medicine is in the range of 1:6:1 to 1:2:1, which has a significant effect on reducing the expression level of inflammatory factors in mice with chronic sinusitis. Further, a traditional Chinese medicine formula for treating chronic sinusitis in children is provided in combination with a composite preparation of probiotics, and surprisingly found that the therapeutic effect of composite preparation 2 is more efficient and significant than that of other composite preparations and control groups, and the traditional Chinese medicine formula and probiotics have a synergistic effect when used in combination at a weight ratio of 10:2. This study is of great significance in providing a preparation with the characteristics of no drug resistance, side effects, and rapid onset for patients with chronic sinusitis in children.

Description

A Chinese medicine composition for treating chronic sinusitis in children and its compound preparation

Technical Field

The invention belongs to the field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine composition for treating chronic sinusitis in children, and a composite preparation and application thereof.

Background Art

Chronic sinusitis mainly occurs in children. The cause of the disease is that children have congenital immune dysfunction and poor disease resistance, and are susceptible to colds, upper respiratory tract infections and acute infectious diseases that induce sinusitis. In addition, not paying attention to nasal hygiene and being prone to secondary sinusitis infections due to nasal foreign bodies and nasal trauma are also the main causes of the disease in children.

If children suffer from chronic sinusitis, they are prone to symptoms such as listlessness, loss of appetite, headache and dizziness. Because children do not know how to blow their noses, the excrement often accumulates in the nasal cavity and sinuses, and even flows back to the pharynx, which will cause severe nasal congestion and mouth breathing, which will lead to stagnation of maxillofacial development. Long-term mouth breathing can make the lips thicker, the teeth protrude outward, the nose bridge flat, the hard palate high and arched, and the teeth unevenly arranged, forming a "sinusitis face".

At present, single anti-inflammatory drugs or traditional Chinese medicine preparations are mostly used in the clinic to treat chronic sinusitis in children. However, because chronic sinusitis is prone to recurrence, long-term use of anti-inflammatory drugs such as glucocorticoids and macrolide antibiotics is prone to drug resistance and adverse reactions, which have a great impact on children's growth and development. The use of traditional Chinese medicine preparations such as sinusitis oral liquids on the market also takes a long time to take effect, and the treatment cycle is long, resulting in poor treatment effects. Therefore, patients with chronic sinusitis are increasingly eager for preparations that have no drug resistance, side effects, and fast onset.

Probiotics are bacteria that are beneficial to the human body. They play an important role in maintaining the balance of intestinal flora, enhancing the function of the immune system, and inhibiting the growth of harmful microorganisms. Bifidobacterium and lactic acid bacteria are the two most widely used probiotics. With the continuous deepening of modern medical research, more and more emphasis is placed on the role of the gut-lung axis in various diseases. Clinically, it is noted that intestinal flora disorders can also be reflected in the respiratory tract, leading to the onset of respiratory diseases. Therefore, the use of probiotics to regulate the intestinal microenvironment to treat chronic sinusitis in children has potential benefits.

Summary of the invention

The purpose of the present invention is to provide a Chinese medicine composition and a compound preparation thereof for treating chronic sinusitis in children. The present invention first provides an optimized Chinese medicine composition, which has an excellent effect of treating chronic sinusitis in children.

On the other hand, the present invention further provides a composite preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children, and surprisingly found that the Chinese medicine composition and probiotics have a synergistic effect when used in combination within an appropriate dosage range, which is of great significance in providing children with chronic sinusitis patients with a preparation that has the characteristics of no drug resistance, side effects, and rapid onset.

In the Chinese medicine composition of the present invention, siler, magnolia flower and xanthium sibiricum are main drugs, mulberry bark and calamus are assistant drugs, luffa and lycium bark are adjuvant drugs, and rhizoma smilacis asiatica, beehive and liquorice are guiding drugs.

Specifically, the present invention first provides a traditional Chinese medicine composition for treating chronic sinusitis in children, which is composed of 5-20 parts of siler, 20-60 parts of magnolia flower, 5-20 parts of xanthium sibiricum, 5-20 parts of mulberry bark, 5-20 parts of calamus, 5-20 parts of luffa, 5-20 parts of lycium bark, 5-20 parts of rhizoma smilacis Glabrae, 2-10 parts of honeycomb, and 2-10 parts of liquorice.

Preferably, the Chinese medicine composition comprises, by weight, 5-15 parts of siler, 30-50 parts of magnolia flower, 5-15 parts of xanthium sibiricum, 5-15 parts of mulberry bark, 5-15 parts of calamus, 5-15 parts of luffa, 5-15 parts of lycium bark, 5-15 parts of liquidambar formosana, 2-10 parts of honeycomb, and 2-10 parts of liquorice.

composition.

More preferably, the Chinese medicine composition is composed, by weight, of 10 parts of Saposhnikovia divaricata, 40 parts of magnolia flower, 10 parts of Xanthium sibiricum, 10 parts of Morus alba bark, 10 parts of Acorus calamus, 10 parts of Luffa fructus, 10 parts of Lycium bark, 10 parts of Smilax glabra, 5 parts of Beehive, and 5 parts of Licorice.

Furthermore, the Chinese medicine composition of the invention can be used together with a pharmaceutical carrier to be prepared into pills, powders, granules, capsules, and clear pastes.

The present invention also provides a method for preparing the above-mentioned Chinese medicine composition for treating chronic sinusitis in children, the steps comprising:

1) Weigh the medicinal materials, wash them, dry them, cut them, grind them and pass them through a fine sieve;

2) Weigh the corresponding powder according to the above weight ratio, soak it in distilled water for 2-3 hours, and then heat it to 90-100° C. with a constant temperature heater. Repeat the decoction of the medicinal materials 2-3 times, adding 5-10 times the total weight of all the original medicinal materials each time, and the decoction time is 3-4 hours. After standing and settling, the filtrate is combined and the supernatant is taken. The supernatant is further concentrated into a paste using a rotary evaporator, and the paste powder is obtained after spray drying, and the corresponding Chinese medicine pills are made according to conventional processes.

On the other hand, the present invention further provides a composite preparation comprising any of the aforementioned Chinese medicine compositions combined with probiotics.

Specifically, the present invention further provides a composite preparation of a Chinese medicine composition for treating chronic sinusitis in children combined with probiotics, which is composed of 100-300 parts by weight of a powder of any Chinese medicine pill prepared by the above method and 10-40 parts by weight of probiotic powder.

Preferably, the composite preparation is composed of 100 parts by weight of any of the powders of the Chinese medicine pills prepared by the above method and 10-20 parts of probiotic powder.

More preferably, the composite preparation is composed, by weight, of 100 parts by weight of any one of the Chinese medicine pills prepared by the above method and 20 parts by weight of probiotic powder.

Preferably, the probiotics are one or more of bifidobacteria and lactic acid bacteria.

Preferably, the probiotic is bifidobacterium.

Preferably, the active content of bifidobacteria in the bacterial powder is 1.0×10 ⁷ -5.0×10 ⁷ CFU.

More preferably, the active content of bifidobacteria in the bacterial powder is 2.0×10 ⁷ CFU.

The present invention also provides a method for preparing the composite preparation of the above-mentioned Chinese medicine composition for treating chronic sinusitis in children combined with probiotics, the steps comprising:

1) Pre-preparation: grind any prepared Chinese medicine pill into powder, pass through a 200-mesh sieve for later use;

2) Mixing: Add the above powder into a batch mixer, add the bacterial powder, and mix in a mixer for 30 minutes;

3) Capsulation: The composite powder mixed in step 2) is filled into capsule shells under nitrogen filling conditions to prepare a capsule composite preparation, and is stored at 2-8°C.

The present invention provides application of the composite preparation of the above-mentioned traditional Chinese medicine composition combined with probiotics in preparing a pharmaceutical preparation for treating chronic sinusitis in children.

Preferably, the pharmaceutical preparation is one or more of capsules, tablets, and ointments.

In the present invention, the pharmacological basis of the Chinese medicine composition is:

Saposhnikovia divaricata: spicy, sweet and slightly warm, it enters the bladder, liver and spleen meridians; "Shennong's Herbal Classic" says that Saposhnikovia divaricata "is used to treat dizziness and headache caused by severe wind, aversion to wind, wind evil, blindness, and pain in the joints throughout the body caused by wind", dispels wind and cold, relieves exterior symptoms and eliminates dampness, and relieves pain and swelling.

Magnolia flower: spicy in taste, slightly warm in nature, enters the lung and stomach meridians; "Shennong's Herbal Classic" says that magnolia flower "treats fever in the five internal organs and body, headache, wind and brain pain", dispels wind and dampness, detoxifies and reduces swelling, disperses blood stasis and relieves pain.

Xanthium sibiricum: pungent, bitter, warm, enters the lung meridian; "Shennong's Herbal Classic" says it "treats wind-induced cold pain in the head, rheumatism, joint pain in the limbs, and dead muscles"; it can clear the nose and dispel wind, regulate qi and blood, and reduce inflammation and relieve pain.

Mulberry bark: sweet and cold, enters the lung and spleen meridians. "Shennong's Herbal Classic" says that it "treats injuries, emaciation due to fatigue and extreme pain, metrorrhagia, pulse loss, and replenishes deficiency and invigorates Qi". It can purge the lungs and relieve asthma, promote diuresis and reduce swelling, activate blood circulation and remove blood stasis, resolve phlegm and stop cough, and promote body fluid and quench thirst.

Acorus calamus: pungent, slightly warm, enters the mouth, liver and spleen meridians; "Shennong's Herbal Classic" says that it "treats wind-cold-dampness arthralgia, cough and shortness of breath, opens the heart orifices, replenishes the five internal organs, unblocks the nine orifices, brightens the ears and eyes, and produces sounds", dispels wind and dampness, opens the orifices and eliminates phlegm, regulates qi and activates blood circulation.

Luffa: sweet, flat, enters the lung, stomach, and liver meridians. "Shennong's Herbal Classic" says that it "opens the meridians, harmonizes the blood vessels, resolves phlegm and smoothes the qi", and can open the meridians, detoxify and reduce swelling, and cool the blood.

Radix Digupi: sweet, cold, enters the lung, liver, and kidney meridians. "Shennong's Herbal Classic" says that it "controls evil qi in the five internal organs, heat in the middle and thirst, and arthralgia", clears heat and cools blood, clears the lungs and reduces fire.

Rhizoma Lulutong: bitter, neutral, enters the liver and kidney meridians. "Compendium of Materia Medica" says that "it can ward off malaria and plague, improve eyesight, remove dampness, relax tendons and tendons, relieve pain in the whole body, pain in the hands, feet and waist, and all can be cured by burning it and smelling its smoke", dispel wind, activate collaterals, promote diuresis and dredge the meridians.

Beehive: sweet and salty, neutral, enters the liver and stomach meridians. "Shennong's Herbal Classic" says that it "treats epilepsy, cold and heat evil spirits, epilepsy, and intestinal hemorrhoids", attacks toxins and disperses knots, dispels wind and relieves pain, benefits the kidney and warms the yang, kills insects and relieves itching.

Licorice: sweet, neutral, enters the heart, lung, spleen, and stomach meridians. "Shennong's Herbal Classic" says that it "controls the cold and heat evil spirits of the five internal organs, strengthens tendons and bones, grows muscles, doubles strength, treats wounds and swellings, and detoxifies", and it nourishes the spleen and replenishes qi, clears away heat and detoxifies, and removes phlegm and relieves cough.

The embodiments of the present invention have at least the following beneficial effects:

The inventors conducted research and first provided an optimized and adjusted Chinese medicine composition, which has an excellent effect of treating chronic sinusitis in children. In the main medicine compatibility of the composition, Saposhnikovia divaricata, Magnolia officinalis, and Xanthium sibiricum belong to an excellent main medicine compatibility system, the ministerial medicines are Morus alba, Lycium bark, Acorus calamus, and Rhizoma Smilacis Glabrae, and the adjuvant medicines are Loofah and Beehive; this compatibility method can give full play to the maximum efficacy and synergistic effect of each Chinese medicine, and the therapeutic effect of the Chinese medicine composition of the present application is also significantly better than similar prescriptions in the prior art. In the invention, the main medicine is pungent and warm to relieve the exterior symptoms, dredge the meridians and open the mind; the ministerial medicine clears the lungs, clears heat and removes dampness; the adjuvant medicine dispels wind and dredges the meridians; the overall therapeutic effect of dredges the lungs, removes dampness, and opens the mind is achieved.

In the composition, siler, magnolia flower and Xanthium sibiricum are used as the main medicines, and the weight ratio of the main medicines 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 mice with chronic sinusitis. It was found that the therapeutic effect of composition group 3 was the best, and the data showed that it has a significant synergistic protective effect on sinus mucosal damage.

Furthermore, a compound preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children is provided, and surprisingly, it is found that the treatment effect of compound preparation 2 is more effective than other compound preparations and the control group, with a cure rate of 80% and an effective rate of up to 100%. The Chinese medicine composition and probiotics have a synergistic effect when used in combination at a weight ratio of 10:2, and the Q value is 1.25, and the Q>1.15. This study is of great significance in providing a preparation with no drug resistance, side effects, and rapid onset for patients with chronic sinusitis in children.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1: HE staining of each group of Chinese medicine compositions for treating chronic sinusitis in children

Figure 2: Q values of the composite preparations of Chinese medicine composition combined with probiotics at different weight ratios

DETAILED DESCRIPTION

The present invention aims to provide a Chinese medicine composition and a composite preparation for treating chronic sinusitis in children, as well as a preparation method and application thereof. The following will be described in detail in conjunction with the contents of the experimental examples, but the scope of the present invention is not limited thereto.

The medicinal materials, auxiliary materials, reagents or instruments used in the embodiments of the present invention without indicating the manufacturer are all conventional products that can be obtained through commercial purchase, and the medicinal materials used all comply with the provisions of the inspection items of various medicinal materials in the first volume of the Chinese Pharmacopoeia, and the auxiliary materials used comply with the usage standards of the fourth volume of the Chinese Pharmacopoeia.

1. Screening test for suitable compatibility range of main drug weight

Example 1.1 A Chinese medicine composition for treating chronic sinusitis in children

A Chinese medicine composition for treating chronic sinusitis in children, wherein 10 parts of siler, 60 parts of magnolia flower, 10 parts of xanthium sibiricum, 10 parts of mulberry bark, 10 parts of calamus, 10 parts of luffa, 10 parts of lycopodii bark, 10 parts of fennel, 10 parts of honeycomb, and 5 parts of liquorice are used as main drugs. The preparation steps include:

1) Weigh the medicinal materials, wash them, dry them, cut them, grind them and pass them through a fine sieve;

2) Weigh the corresponding powder according to the above weight ratio, soak it in distilled water for 2-3 hours, and then heat it to 90-100°C with a constant temperature heater. Repeat the decoction of the medicinal materials for 2-3 times, adding 5-10 times the total weight of all the original medicinal materials each time, and the decoction time is 3-4 hours. After standing and settling, the filtrate is combined and the supernatant is taken. The supernatant is further concentrated into a paste using a rotary evaporator, and the paste powder is obtained after spray drying, and the corresponding Chinese medicine pills 1 are prepared according to conventional processes.

Example 1.2 A Chinese medicine composition for treating chronic sinusitis in children

A Chinese medicine composition for treating chronic sinusitis in children, wherein 10 parts of siler, 40 parts of magnolia flower, 10 parts of xanthium sibiricum, 10 parts of mulberry bark, 10 parts of calamus, 10 parts of luffa, 10 parts of lycopodii root, 10 parts of fennel, 5 parts of honeycomb, and 5 parts of liquorice are used as main drugs (weight ratio: 1:4:1). A Chinese medicine pill 2 is prepared according to the above preparation method.

Example 1.3 A Chinese medicine composition for treating chronic sinusitis in children

A Chinese medicine composition for treating chronic sinusitis in children, wherein 10 parts of siler, 20 parts of magnolia flower, 10 parts of xanthium sibiricum, 10 parts of mulberry bark, 10 parts of calamus, 10 parts of luffa, 10 parts of lycopodii root, 10 parts of fennel, 10 parts of honeycomb, and 5 parts of liquorice are used as main drugs (weight ratio: 1:2:1). A Chinese medicine pill 3 is prepared according to the above preparation method.

Example 1.4 A Chinese medicine composition for treating chronic sinusitis in children

A Chinese medicine composition for treating chronic sinusitis in children, wherein 10 parts of siler, 10 parts of magnolia flower, and 10 parts of xanthium sibiricum are the main drugs (weight ratio: 1:1:1), and the composition comprises 10 parts of siler, 10 parts of magnolia flower, 10 parts of xanthium sibiricum, 10 parts of mulberry bark, 10 parts of calamus, 10 parts of luffa, 10 parts of lycium bark, 10 parts of fennel, 10 parts of honeycomb, and 5 parts of liquorice. A Chinese medicine pill 4 is prepared according to the above preparation method.

Comparative Example 1.5: Prior art (Cai Xiling. Clever use of ephedra to treat chronic diseases [J]. Chinese Community Physician (Medical Specialty), 2012, 14 (17): 229.) discloses a Chinese medicine composition for treating chronic rhinitis or allergic rhinitis, wherein the Chinese medicine components for treating chronic rhinitis or allergic rhinitis are 10g of magnolia, 10g of Xanthium sibiricum, 10-15g of Saposhnikovia divaricata, and 10-30g of Rhizoma Smilacis Glabrae; based on the composition disclosed in this document, 10 parts of magnolia, 10 parts of Xanthium sibiricum, 10 parts of Saposhnikovia divaricata, and 10 parts of Rhizoma Smilacis Glabrae were taken by weight, and a Chinese medicine comparison pill 1 was prepared according to the above preparation method.

Comparative Example 1.6: In order to explore the effect of the combination of Saposhnikovia divaricata, Magnolia officinalis, and Xanthium sibiricum as the main medicine, further, on the basis of Example 1, this study removed Saposhnikovia divaricata and only used Magnolia officinalis and Xanthium sibiricum as the main medicine to obtain a Chinese medicine composition for treating chronic sinusitis in children, specifically: by weight, Magnolia officinalis and Xanthium sibiricum are the main medicines (weight ratio: 6:1), consisting of Magnolia officinalis 60, Xanthium sibiricum 10, Morus alba 10, Acorus tatarinowii 10, Luffa 10, Lycium bark 10, Fructus Lycii 10, Fructus Smilacis Glabrae 10, Beehive 5, and Licorice 5. The Chinese medicine comparative pill 2 was prepared according to the above preparation method.

Example 1.7 Experimental study on the efficacy of Chinese medicine composition 1-4 and control group 1-2 in treating chronic sinusitis in children

28 C57BL/6J mice (purchased from the Experimental Animal Center of Sun Yat-sen University, randomly divided into 7 groups according to body weight, 4 mice in each group), with an average body weight of 20±2g, were placed in a closed box at a temperature of 25-26°C and a humidity of 70% for adaptive feeding, and the experiment was conducted 10 days later. The 28 mice were randomly divided into a model group, a composition group 1, a composition group 2, a composition group 3, a composition group 4, a control group 1, and a control group 2. After the mice were anesthetized, a scalpel was used to make a transverse incision of about 2 mm in the middle of the nasal dorsum of the mice, and the subcutaneous fat and other tissues were separated to expose the sinus cavity to the outside. A small hole with a diameter of about 0.5 mm was immediately picked out at the openings on both sides of the maxillary sinus with the tip of the knife, and the cotton containing 10 μl of type 3 capsule pneumococcal strain (ATCC49619 pneumococcal strain: purchased from Shanghai Shenggong) bacterial liquid was transplanted into the sinus cavity. Finally, the skin was sutured with needle and thread, and the overflowed tissue fluid was wiped with alcohol to establish a chronic sinusitis mouse model. In the second week after the successful modeling, mice in group 1, group 2, group 3, group 4, control group 1, and control group 2 were all gavaged at a dose of 5 g/kg, and the model group was gavaged with an equal amount of normal saline. The frequency of administration was 3 times/day, and the administration was continued for 3 weeks, and the symptoms of mice in each group were observed.

Peripheral blood inflammatory factor levels: 12 hours after the last administration, 1 ml of aortic blood was collected from each group of mice. The blood was allowed to stand for 0.5 hours and then centrifuged at 4000 r/min for 15 minutes. The upper serum was collected using a sterile pipette, and then the expression levels of TNF-α and IL-6 inflammatory factors in the peripheral blood of mice were determined by ELISA. The results are shown in Table 1.

Pathological changes of sinus mucosal tissue: 3 weeks after administration, the mice were killed, and the corresponding sinus mucosal tissues were taken out on a clean bench, fixed with 4% paraformaldehyde solution, and sliced using HE staining. The pathological changes of sinus mucosal tissues were observed under a light microscope. The HE staining slides are shown in Figure 1.

Table 1: Expression levels of TNF-α and IL-6 inflammatory factors in mouse peripheral blood

Results: In terms of the general state of mice, before modeling, the 7 groups of mice all had normal diets, good mental states, normal activities, shiny fur, and no chronic sinusitis symptoms such as nasal congestion, runny nose, and sneezing. Two days after modeling, the mice all had severe runny nose, scratching nose, and sneezing. After administration, the mice in the model group still had severe runny nose, scratching nose, and sneezing, which were alleviated to varying degrees by administration of composition 1-4 and control group 1-2. The phenomenon of mice in composition 1 and 3 groups was milder than that in composition 2 and 4 groups, and the degree of improvement of the symptoms of mice in composition 1-4 was superior to that of control group 1-2.

As shown in Table 1, the levels of TNF-α and IL-6 in the peripheral blood of the model group mice were high, but the levels of inflammatory factors in the administration composition 1-4 groups were lower than those in the model group, among which the difference in the administration composition 1-3 groups was statistically significant (P<0.05), and the effect of reducing inflammatory factors in the administration composition 1-4 groups relative to the comparison group 1-2 was also statistically significant (P<0.05). As can be seen from the results, in the monarch drug compatibility, Saposhnikovia divaricata, Magnolia officinalis, and Xanthium sibiricum belong to an excellent monarch drug compatibility system, and its organic compatibility method can exert the maximum efficacy and synergistic effect of each Chinese medicine, and the therapeutic effect of the Chinese medicine composition of the present application is also significantly better than the related prescriptions in the prior art.

The applicant also found that in the Chinese medicine composition for treating chronic sinusitis in children, when Saposhnikovia divaricata, Magnolia officinalis, and Xanthium sibiricum are used as the main medicine, the weight ratio of the main medicine is different, and the effect on the expression level of inflammatory factors is also different. Among them, the weight ratio of the main medicine in the range of 1:6:1 to 1:2:1 has a significant effect on the expression level of inflammatory factors in mice with chronic sinusitis, and it is also found that with the increase of the weight of Magnolia officinalis in the main medicine, its effect does not show a simple dose dependence. Composition group 3 (weight ratio: 1:2:1) has a significant reduction in regulating the expression level of inflammatory factors compared with composition group 4 (weight ratio: 1:1:1), but the increase of the weight of Magnolia officinalis in the main medicine, the effect of composition 1-2 does not show dose dependence, and the therapeutic effect of composition group 3 is relatively poor. It can be seen that in this Chinese medicine composition, the weight ratio range of the main medicine has a significant impact on its overall therapeutic effect.

And from the HE staining results of Figure 1, it can be seen that the nasal mucosa of the model group showed more serious chronic inflammation, and its mucosal epithelial cells were unevenly distributed, with a large number of epithelial cell necrosis, shedding, fibrosis and other symptoms, and obvious inflammatory cell infiltration. The administration compositions 1-4 and the comparison group all had different degrees of improvement or relief, especially the composition 3 group, and its degree of improvement was significantly better than other administration compositions and the comparison group. After the drug administration treatment, the epithelial cells were clearly and neatly distributed, and there was no obvious infiltration of inflammatory cells in the submucosal layer, and there was no glandular hyperplasia. The results showed that it had a significant synergistic protective effect on sinus mucosal damage.

Based on the above results and taking into account the cost of medication, subsequent experiments used composition 3 in combination with probiotics to explore the preparation of a more efficient compound preparation.

2. Exploration test of high-efficiency compound preparation of composition 3 combined with probiotics

Example 2.1 A compound preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children 1

A composite preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children, which is composed of a Chinese medicine composition part and a probiotic part, wherein the Chinese medicine composition part: by weight, 100 parts of powder ground from a Chinese medicine pill composition 3; the probiotic part: by weight, 10 parts of bifidobacterium powder with an active content of 2.0×10 ⁷ CFU, and the preparation steps thereof include: 1) pre-preparation: grinding the prepared Chinese medicine pill composition 3 into powder, and passing it through a 200-mesh sieve for standby use;

2) Mixing: Add the above powder into a batch mixer, add Bifidobacterium powder, and mix in a mixer for 30 minutes;

3) Capsulation: The composite powder mixed in step 2) is filled into a capsule shell under nitrogen filling conditions to obtain a capsule composite preparation 1, and is stored at 2-8°C.

Example 2.2 A compound preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children 2

A composite preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children, which is composed of a Chinese medicine composition part and a probiotic part, wherein the Chinese medicine composition part: counted by weight, a powder 100 of a Chinese medicine pill composition 3 ground into powder; the probiotic part: counted by weight, a bifidobacterium powder 20 with an active content of 2.0×10 ⁷ CFU, is prepared according to the above-mentioned preparation method to obtain a composite preparation 2.

Example 2.3 A compound preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children 3

A composite preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children, which is composed of a Chinese medicine composition part and a probiotic part, wherein the Chinese medicine composition part: counted by weight, 100 parts of powder ground from a Chinese medicine pill composition 3; the probiotic part: counted by weight, 30 parts of bifidobacterium powder with an active content of 2.0×10 ⁷ CFU, the composite preparation 3 is prepared according to the above preparation method.

Example 2.4 A compound preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children

A composite preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis in children, which is composed of a Chinese medicine composition part and a probiotic part, wherein the Chinese medicine composition part: counted by weight, a powder 100 of a Chinese medicine pill composition 3 ground into powder; the probiotic part: counted by weight, a bifidobacterium powder 40 with an active content of 2.0×10 ⁷ CFU, prepared according to the above-mentioned preparation method to obtain a composite preparation 4.

Example 2.5 Control group 1: Chinese medicine composition for treating chronic sinusitis in children:

A Chinese medicine composition for treating chronic sinusitis in children, which is composed only of Chinese medicines. 100 parts by weight of the powder ground from the Chinese medicine composition 3 are filled into capsule shells according to the preparation method to prepare a control group 1.

Example 2.6 Control group 2: Bifidobacterium powder:

A bifidobacterium powder, counted by weight, is prepared by filling bifidobacterium powder 20 with an active content of 2.0×10 ⁷ CFU into a capsule shell according to the above preparation method to prepare a control group 2.

Example 2.7 Experimental study on the efficacy of compound preparations 1-4 in treating chronic sinusitis in children

Case source: Patients with chronic sinusitis admitted to the outpatient and inpatient departments of the Affiliated Hospital of Traditional Chinese Medicine of Guangzhou Medical University from January 2023 to June 2023 were selected as the research subjects.

Inclusion criteria:

1) Patients diagnosed with chronic sinusitis and meeting the diagnostic criteria for chronic sinusitis in the Guidelines for the Diagnosis and Treatment of Chronic Rhinosinusitis.

2) Aged no more than 14 years old, with no heart, liver, kidney, brain or other diseases

3) Obtain consent from the patient’s parents and have them sign an informed consent form

4) No relevant medication or other treatment has been received in the past week.

Exclusion criteria:

1) Those who do not meet the inclusion and diagnostic criteria;

2) Aged over 14 years;

3) Patients with severe systemic diseases of the liver, kidney, heart, blood system, etc., and mental illnesses;

4) Those with allergic constitution or allergic to the ingredients of the prescriptions and medicines in this trial, or those who are unable to cooperate with the treatment.

Experimental method: 60 children with chronic sinusitis were selected as the research subjects and randomly divided into 6 groups. Ten cases were enrolled in the combined preparation treatment groups 1-4 and the control groups 1-2, 5 males and 5 females, aged no more than 14 years old. All patients received a 4-week treatment after enrollment.

Efficacy evaluation: After treatment, the clinical symptoms and signs of patients with chronic sinusitis disappeared, the CT examination results of the sinus cavity showed recovery, and the symptom score decreased by ≥95%, which was recorded as cured; after treatment, the clinical symptoms and signs of patients with chronic sinusitis were effectively improved, the CT examination results of the sinus cavity showed basic recovery, and the symptom score decreased by 70% to 95%, which was recorded as markedly effective; after treatment, the clinical symptoms and signs of patients with chronic sinusitis were improved, the CT examination results of the sinus cavity showed improvement, and the symptom score decreased by 30% to 70%, which was recorded as effective; if the above standards were not met, it was recorded as ineffective. The results are shown in Table 2.

Peripheral blood inflammatory factor levels of patients: After the last administration, the patient fasted for 12 hours, and 5 ml of blood was drawn from the arm vein the next morning. Serum was separated after centrifugation, and the inflammatory factors were detected by an automatic biochemical analyzer to determine the expression levels of TNF-α and IL-6 inflammatory factors in peripheral blood. The results are shown in Table 3.

Table 2 Comparison of clinical efficacy between the combined preparation treatment group and the control group

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

Results: From the clinical efficacy comparison data of the compound preparation treatment group and the control group in Table 2, it can be seen that the cure rate and effective rate of the compound preparations 1-4 (the weight ratio of the powder of the compound 3 to the bifidobacterium powder ranges from 10:1 to 10:4) of the Chinese medicine composition combined with probiotics are significantly improved compared with the control group 1 (composition 3 powder) and the control group (bifidobacterium powder), which has significant statistical significance (*P<0.05). It can be seen that the Chinese medicine composition combined with probiotics has a significant therapeutic effect on chronic sinusitis in children. Furthermore, among the compound preparations 1-4, the compound preparation 2 with a weight ratio of 10:2 is more effective than the other compound preparations, with a cure rate of 80% and an effective rate of up to 100%. Similarly, the data on the expression levels of inflammatory factors TNF-α and IL-6 in peripheral blood in Table 3 further verified that the Chinese medicine composition combined with probiotics has a synergistic effect in the treatment of chronic sinusitis in children. Composite preparation 2 can reduce the level of TNF-α to about 10.63±1.98ng/L, and the level of IL-6 to about 14.16±1.78, which is extremely statistically significant (**P<0.01).

Furthermore, we used King's formula to evaluate the therapeutic effect of the weight ratio of the above-mentioned composition 3 powder to the bifidobacterium powder in the range of 10:1 to 10:4. The conventional King's formula stipulates 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 shown in Figure 2.

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

The protection scope of the present invention is not limited to the above-mentioned embodiments. Any equivalent substitution or change made by a person skilled in the art based on the present invention is within the protection scope of the present invention. The protection scope of the present invention is subject to the claims.

Claims (9)

1. A Chinese medicine composition for treating chronic sinusitis, characterized in that, by weight, it consists of 5-20 parts of Saposhnikovia divaricata, 20-60 parts of Magnolia officinalis flower, 5-20 parts of Xanthium sibiricum fruit, 5-20 parts of Morus alba bark, 5-20 parts of Acorus calamus, 5-20 parts of Luffa fructus, 5-20 parts of Lycium bark, 5-20 parts of Fructus liquidambar formosana, 2-10 parts of Beehive, and 2-10 parts of Licorice. 2. The Chinese medicine composition as claimed in claim 1, characterized in that it is composed of 10 parts of Saposhnikovia divaricata, 40 parts of Magnolia officinalis flowers, 10 parts of Xanthium sibiricum, 10 parts of Morus alba bark, 10 parts of Acorus calamus, 10 parts of Luffa gourd, 10 parts of Lycium bark, 10 parts of Fructus Liquidambar formosana, 5 parts of Beehive, and 5 parts of Licorice. 3. A preparation prepared from the Chinese medicine composition according to any one of claims 1 to 2, characterized in that the preparation also includes a pharmaceutical carrier. 4. The preparation prepared from the Chinese medicine composition according to any one of claims 1 to 3, characterized in that the preparation is a pill, a capsule, a clear paste or a granule. 5. A method for preparing the Chinese medicine composition according to any one of claims 1 to 4, comprising the steps of: 1) Weigh the medicinal materials, wash them, dry them, cut them, grind them and pass them through a fine sieve; 2) Weigh the corresponding powder according to the above weight ratio, soak it in distilled water for 2-3 hours, and then heat it to 90-100° C. with a constant temperature heater. Repeat the decoction of the medicinal materials 2-3 times, adding 5-10 times the total weight of all the original medicinal materials each time, and the decoction time is 3-4 hours. After standing and settling, the filtrate is combined and the supernatant is taken. The supernatant is further concentrated into a paste using a rotary evaporator, and the paste powder is obtained after spray drying, and the corresponding Chinese medicine preparation is prepared according to conventional processes. 6. A composite preparation of a Chinese medicine composition combined with probiotics for treating chronic sinusitis, characterized in that, by weight, it consists of 100-300 parts by weight of the powder of the Chinese medicine prepared by the method of claim 5 and 10-40 parts by weight of probiotic powder. 7. The use according to claim 6, characterized in that it is composed of the powder 100 and the probiotic powder 20 in parts by weight. 8. The use according to claim 7, characterized in that the bacterial powder is bifidobacterium powder with an active content of 2.0× ¹⁰⁷ CFU. 9. A method for preparing the composite formulation according to any one of claims 6 to 8, comprising the steps of: 1) Pre-preparation: grind any prepared Chinese medicine preparation into powder, pass through a 200-mesh sieve for later use; 2) Mixing: Add the above powder into a mixer, add the bacterial powder, and mix in the mixer for 30 minutes; 3) Capsulation: The composite powder mixed in step 2) is filled into capsule shells under nitrogen filling conditions to prepare a capsule composite preparation, and is stored at 2-8°C.