Use of a traditional Chinese medicine composition in the preparation of a drug for treating sinusitis

Abstract

This invention relates to the application of a traditional Chinese medicine composition in the preparation of a drug for sinusitis. The composition is characterized by being prepared from ephedra (processed with honey), bitter almond, perilla seed, prepared pinellia, licorice, scutellaria, angelica, belamcanda, coltsfoot flower, mulberry bark, cicada slough, silkworm, and earthworm. The composition of this invention improves sinusitis symptoms, reduces inflammation levels, and regulates the pH of nasal secretions in a sinusitis model prepared by Staphylococcus aureus, suggesting that this traditional Chinese medicine composition has a good therapeutic effect on sinusitis.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology and relates to a new use of a traditional Chinese medicine composition, specifically the application of a traditional Chinese medicine composition in the preparation of a drug for sinusitis. Background Technology

[0002] Sinusitis is a nonspecific inflammation of the sinus mucosa and a common otolaryngological disease. Inflammation of one or more sinuses is called sinusitis, and the sinuses involved include the maxillary sinus, ethmoid sinus, frontal sinus, and sphenoid sinus. Sinusitis can be divided into acute and chronic types. Acute purulent sinusitis often follows acute rhinitis; persistent acute purulent sinusitis can develop into chronic purulent sinusitis. Maxillary sinusitis is the most common type of sinusitis, followed by inflammation of the ethmoid, frontal, and sphenoid sinuses. Sinusitis can occur singly or in multiple sinuses. If all sinuses are involved, it is called pansinusitis. Acute sinusitis is often caused by upper respiratory tract infections, and bacterial and viral infections can occur simultaneously. Chronic sinusitis is more common than acute sinusitis and often involves multiple sinuses simultaneously. Sinusitis is one of the common diseases in otolaryngology. Although its disability and mortality rates are extremely low, it has become one of the diseases that most significantly impact the health and quality of life of Chinese citizens. The main treatment recommendations for sinusitis in European and Chinese guidelines remain medical treatment centered on corticosteroids and surgical treatment centered on functional endoscopic sinus surgery to remove lesions. This is of great significance for the search and development of effective drugs for treating sinusitis. Summary of the Invention

[0003] To address the aforementioned technical problems, this invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for sinusitis. This composition is prepared from ephedra (processed with honey), bitter almond, perilla seed, mulberry bark, scutellaria, cicada slough, silkworm, earthworm, angelica root, belamcanda rhizome, coltsfoot flower, prepared pinellia tuber, and licorice. The term "used for" can refer to any method beneficial to improving the corresponding symptoms of the patient, including treatment or prevention.

[0004] Specifically, the use for sinusitis includes symptoms such as nasal obstruction, purulent nasal discharge, localized pain, and / or headache.

[0005] Further, the traditional Chinese medicine composition includes: 150-250 parts of honey-processed ephedra, 200-300 parts of bitter almond, 150-250 parts of perilla seed, 350-450 parts of mulberry bark, 350-450 parts of scutellaria, 200-300 parts of cicada slough, 200-300 parts of silkworm, 350-450 parts of earthworm, 200-300 parts of angelica root, 300-400 parts of belamcanda rhizome, 350-450 parts of coltsfoot flower, 200-300 parts of prepared pinellia tuber, and 150-250 parts of licorice root. The composition of this invention can be directly ground into powder, or it can be an extract obtained through conventional methods in the art. The traditional Chinese medicines used in the composition of this invention can also be used by directly grinding into powder, extracting, or in other processed forms.

[0006] Furthermore, the traditional Chinese medicine composition includes: 170-230 parts of honey-processed ephedra, 240-280 parts of bitter almond, 170-230 parts of perilla seed, 370-430 parts of mulberry bark, 370-430 parts of scutellaria, 240-280 parts of cicada slough, 240-280 parts of silkworm, 370-430 parts of earthworm, 240-280 parts of angelica root, 300-350 parts of belamcanda rhizome, 370-430 parts of coltsfoot flower, 240-280 parts of prepared pinellia tuber, and 170-230 parts of licorice root.

[0007] Further, the traditional Chinese medicine composition includes: 180-200 parts of honey-processed ephedra, 250-270 parts of bitter almond, 180-200 parts of perilla seed, 380-400 parts of mulberry bark, 380-400 parts of scutellaria, 250-270 parts of cicada slough, 250-270 parts of silkworm, 380-400 parts of earthworm, 250-270 parts of angelica root, 330-350 parts of belamcanda rhizome, 380-400 parts of coltsfoot flower, 250-270 parts of prepared pinellia tuber, and 180-200 parts of licorice root.

[0008] Preferably, the traditional Chinese medicine composition includes: 200 parts of honey-processed ephedra, 266.7 parts of bitter almond, 200 parts of perilla seed, 400 parts of mulberry bark, 400 parts of scutellaria, 266.7 parts of cicada slough, 266.7 parts of silkworm, 400 parts of earthworm, 266.7 parts of angelica root, 333.3 parts of belamcanda rhizome, 400 parts of coltsfoot flower, 266.7 parts of prepared pinellia tuber, and 200 parts of licorice.

[0009] This invention also proposes the use of the traditional Chinese medicine composition as described in any of the preceding claims in the preparation of anti-inflammatory drugs. The inflammation, or the aforementioned sinusitis, may optionally be caused by Staphylococcus aureus.

[0010] Specifically, the aforementioned drugs are selected from decoctions, granules, capsules, tablets, oral liquids, pills, soft capsules, drop pills, tinctures, syrups, suppositories, gels, sprays, and injections.

[0011] This invention also proposes a method for preparing the traditional Chinese medicine composition as described above, comprising:

[0012] a. Take five medicinal materials: honey-processed ephedra, bitter almond, perilla seed, prepared pinellia, and licorice. Add 10 times the amount of water and decoct three times, each time for 1.5 hours. Filter the decoction, concentrate the filtrate under reduced pressure, cool to room temperature, and precipitate with alcohol. Gradually increase the ethanol concentration of the extract concentrate to 75% in a gradient manner, and let it stand for 24 hours. Take the supernatant of the alcohol precipitation and concentrate it under reduced pressure.

[0013] b. Take five medicinal materials: Scutellaria baicalensis, Peucedanum praeruptorum, Belamcanda chinensis, Tussilago farfara, and Morus alba root bark. Add 8 times the amount of 70% ethanol and reflux extract twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure.

[0014] c. Take cicada molting, silkworm pupa, and earthworm, add 8 times the amount of water and decoct twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure. Combine the above concentrates, concentrate under reduced pressure, and dry.

[0015] This invention also provides a method for preparing a medicament for treating or preventing sinusitis as described above, wherein the medicament is selected from granules, and the preparation method is as follows:

[0016] a. Take five medicinal materials: honey-processed ephedra, bitter almond, perilla seed, prepared pinellia, and licorice. Add 10 times the amount of water and decoct three times, 1.5 hours each time. Filter the decoction and concentrate the filtrate under reduced pressure to a relative density of 1.08-1.10 (70℃). Cool to room temperature and precipitate with alcohol. Gradually increase the ethanol concentration of the extract concentrate to 75% (measured with a 25℃ alcohol meter) in a gradient manner. Let it stand for 24 hours. Take the supernatant of the alcohol precipitation and concentrate it under reduced pressure to a relative density of 1.10-1.12 (70℃).

[0017] b. Take five medicinal materials: Scutellaria baicalensis, Peucedanum praeruptorum, Belamcanda chinensis, Tussilago farfara, and Morus alba root bark. Add 8 times the amount of 70% ethanol and reflux extract twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure until there is no alcohol taste (relative density 1.10-1.12, 70℃).

[0018] c. Take cicada molting, silkworm pupa, and earthworm, add 8 times the amount of water and decoct twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure to a relative density of 1.10-1.12 (70℃). Combine the above concentrates and concentrate under reduced pressure to an extract with a relative density of 1.25-1.27 (70℃). Dry and pulverize to obtain an intermediate of the traditional Chinese medicine composition. Add dextrin and aspartame, mix evenly, wet granulate, boil dry to make granules, and obtain the final product.

[0019] The composition of this invention can significantly improve symptoms such as nasal mucosal epithelial congestion, nasal rhinorrhea, or nasal congestion in rats with sinusitis; it can significantly reduce serum TNF-α, IL-6, and IFN-γ inflammatory factors induced by Staphylococcus aureus in rats, and regulate the pH value of nasal secretions, suggesting that the traditional Chinese medicine composition can significantly inhibit the development of inflammation and improve the symptoms of sinusitis in rats, thus having a good therapeutic effect on sinusitis. Detailed Implementation

[0020] As mentioned above, the present invention aims to provide an application of a traditional Chinese medicine composition in the preparation of a drug for sinusitis. The following will describe this in detail with reference to specific experiments.

[0021] Unless otherwise specified, all experiments in the following experiments were conducted under standard conditions or conditions recommended by the manufacturer. Active pharmaceutical ingredients (APIs) or excipients, as well as reagents or instruments whose manufacturers are not specified, are all commercially available products. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention.

[0023] Example 1: Preparation of the Traditional Chinese Medicine Composition

[0024] Ingredients: 200g honey-processed ephedra, 266.7g bitter almond, 200g perilla seed, 400g mulberry bark, 400g scutellaria, 266.7g cicada slough, 266.7g silkworm, 400g earthworm, 266.7g angelica root, 333.3g belamcanda rhizome, 400g coltsfoot flower, 266.7g prepared pinellia tuber, 200g licorice root.

[0025] The preparation method of this traditional Chinese medicine composition granules is as follows:

[0026] a. Take five medicinal materials: honey-processed ephedra, bitter almond, perilla seed, prepared pinellia, and licorice. Add 10 times the amount of water and decoct three times, 1.5 hours each time. Filter the decoction and concentrate the filtrate under reduced pressure to a relative density of 1.08-1.10 (70℃). Cool to room temperature and precipitate with alcohol. Gradually increase the ethanol concentration of the extract concentrate to 75% (measured with a 25℃ alcohol meter) in a gradient manner. Let it stand for 24 hours. Take the supernatant of the alcohol precipitation and concentrate it under reduced pressure to a relative density of 1.10-1.12 (70℃).

[0027] b. Take five medicinal materials: Scutellaria baicalensis, Peucedanum praeruptorum, Belamcanda chinensis, Tussilago farfara, and Morus alba root bark. Add 8 times the amount of 70% ethanol and reflux extract twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure until there is no alcohol taste (relative density 1.10-1.12, 70℃).

[0028] c. Take cicada molting, silkworm pupa, and earthworm, add 8 times the amount of water and decoct twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure to a relative density of 1.10-1.12 (70℃). Combine the above concentrates and concentrate under reduced pressure to an extract with a relative density of 1.25-1.27 (70℃). Dry and pulverize to obtain an intermediate of the traditional Chinese medicine composition. Add dextrin and aspartame, mix evenly, wet granulate, boil dry to make granules, and obtain the final product.

[0029] Experimental Example 2: Effects of Traditional Chinese Medicine Composition on Sinusitis

[0030] 1. Experimental Materials

[0031] 1.1 Animals

[0032] SD rats, male, clean grade, 42 rats, weighing 200-220 grams.

[0033] 1.2 Drugs

[0034] The intermediates of the traditional Chinese medicine composition prepared in Example 1 were from Jiangsu Kangyuan Pharmaceutical Co., Ltd.; isoflurane (Shandong Ante Animal Husbandry Technology Co., Ltd., batch number: Veterinary Drug No. 151987015); sodium pentobarbital (Beijing Chemical Reagent Co., Ltd., batch number: 211122); IL-10 (Wuhan Boster Biological Technology Imaging Co., Ltd., batch number: 138191031117), TNF-α (Wuhan Boster Biological Technology Imaging Co., Ltd., batch number: 240191051109), and IL-6 (Wuhan Boster Biological Technology Imaging Co., Ltd., batch number: 13319811108).

[0035] 1.3 Instruments

[0036] Refrigerator (Haier, model: BCD-216SZ); Electronic balance (Sartorius Scientific Instruments, model: BSA224S-CW); Purified water instrument (Milli-Q Plus, Germany).

[0037] 2. Dosage design

[0038] The daily dosage of the traditional Chinese medicine composition is 117g of raw herbs / day. Based on the body surface area calculation method, the equivalent dose for rats is 117g / 60kg*6.2=12.09g / kg. This dose is taken as the medium dose. According to the 0.5:1:2 dosing method, the low dose is 4.03g / kg and the high dose is 36.27g / kg.

[0039] 3. Experimental Methods

[0040] SD rats were acclimatized for one week before the experiment, with free access to food and water. Rats were randomly divided into three groups (n=8 per group): a sham-operated group, a model control group, and groups receiving low, medium, and high doses (4.03 g / kg, 12.09 g / kg, and 36.27 g / kg) of the traditional Chinese medicine composition. After general anesthesia, 2.0 ml (20 mg / ml) lidocaine combined with 0.0125 mg epinephrine was administered via infiltration anesthesia under the nose. Simultaneously, a 45° incision was made at the junction of the middle third of the rat's face, and 0.1 ml (1×10⁻⁶) of the traditional Chinese medicine composition was inserted. 9 A gelatin sponge containing Staphylococcus aureus (U / L) (ATCC 27217) was inserted into the incision, which was then sutured and disinfected. The sham surgery group underwent the same procedure, but without the implantation of the gelatin sponge containing Staphylococcus aureus.

[0041] Detection indicators: Successful model establishment was defined as follows: three days post-surgery, rats showed decreased activity and food intake; four days post-surgery, rats exhibited nasal scratching and sneezing; five days post-surgery, rats showed significantly reduced activity compared to normal rats; nasal discharge was either thick or clear; and symptoms such as nasal scratching, sneezing, and nasal vestibule redness were observed. Symptoms of the rat acute sinusitis model were scored according to Table 1. The experimental groups were administered a traditional Chinese medicine composition, while the normal and model groups were administered an equal dose of physiological saline by gavage once daily for 7 consecutive days.

[0042] Peripheral blood inflammatory factor levels were detected by ELISA: 24 hours after the last administration, sterile blood was collected from the abdominal aorta of rats, allowed to stand for 2 hours, centrifuged at 3000 r / min for 15 min at room temperature, and the supernatant serum was collected and stored at -80℃ for later use. The expression levels of IL-10, IL-6, and TNF-α in rat peripheral blood were determined by ELISA according to the manufacturer's instructions.

[0043] Nasal pH Measurement: The acidity or alkalinity of nasal mucus or secretions can affect the activity of nasal mucosal cilia and the activity of nasal lysozyme, and can be used to assess the nasal environment and the pathological state of the nasal mucosa. Normal mucosal pH ranges from 5.3 to 7.0, while the pH of sinusitis mucosal pH ranges from 6.8 to 7.6. Seven days after drug administration, the nasal pH of rats in each group was measured. Precision test strips were cut to approximately 2mm × 20mm. The rat's head was fixed, and after disinfection of the nasal vestibule, the pH test strip was inserted into the nasal cavity using ophthalmic forceps, adhering tightly to the mucosa. After 30 seconds, the strip was removed and compared with a standard colorimetric card to read the pH value of the nasal secretions on that side. The average pH value of both nasal cavities was taken.

[0044] Table 1 Symptom scores of rat acute sinusitis model

[0045]

[0046]

[0047] 4. Experimental Results

[0048] The results showed that compared with the normal group, the rats in the model group gradually reduced their food intake and activity levels, exhibited nasal vestibule redness, and frequently experienced nasal irritation and sneezing. The symptom scores of the model group rats were recorded, with a total score ≥5, indicating the successful establishment of a Staphylococcus aureus-induced rat sinusitis model. Compared with the model group, the medium and high doses of the traditional Chinese medicine composition significantly improved the sinusitis symptoms in rats (Table 2) and reduced the serum levels of IL-10, IL-6, and TNF-α cytokines (Table 3), suggesting that the traditional Chinese medicine composition has a good therapeutic effect on sinusitis and inflammation. Compared with the blank group, the pH value of nasal secretions in the model group rats was significantly increased, and the pH decreased to varying degrees after seven days of administration (Table 4), indicating that the nasal inflammation in rats was improved.

[0049] Table 2. Effects of traditional Chinese medicine composition on sinusitis scores in rats ( n=8)

[0050] Group Before administration After administration Sham surgery group 0.25±0.43 0.125±0.33 Model group <![CDATA[9.88±1.36 #### ]]> <![CDATA[8.13±1.90 #### ]]> Low-dose group of traditional Chinese medicine composition 9.75±0.97 <![CDATA[3.63±1.73 *** ]]> Medium Dosage Group of Traditional Chinese Medicine Composition 9.63±0.86 <![CDATA[3.5±2.24 *** ]]> High-dose group of traditional Chinese medicine composition 9.88±1.17 <![CDATA[3.38±2.18 *** ]]>

[0051] Note: Compared with the normal group #### P<0.0001; compared with the model group, ***P<0.001.

[0052] Table 3 Comparison of peripheral blood inflammatory factors in rats from different groups (pg / ml)

[0053]

[0054]

[0055] Note: Compared with the normal group #### P<0.0001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.001.

[0056] Table 4. Nasal secretion values ​​of rats in each group

[0057]

[0058] Note: Compared with the normal group ## P<0.01; compared with the model group, **P<0.01.

[0059] The above embodiments of the present invention are merely examples to clearly illustrate the present invention and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. The application of a traditional Chinese medicine composition in the preparation of a drug for sinusitis, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following components: 170-230 parts of honey-processed ephedra, 240-280 parts of bitter almond, 170-230 parts of perilla seed, 370-430 parts of mulberry bark, 370-430 parts of scutellaria, 240-280 parts of cicada slough, 240-280 parts of silkworm pupa, 370-430 parts of earthworm, 240-280 parts of angelica dahurica, 300-350 parts of belamcanda chinensis, 370-430 parts of coltsfoot flower, 240-280 parts of prepared pinellia, and 170-230 parts of licorice.

2. The application according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following components: 200 parts of honey-processed ephedra, 266.7 parts of bitter almond, 200 parts of perilla seed, 400 parts of mulberry bark, 400 parts of scutellaria, 266.7 parts of cicada slough, 266.7 parts of silkworm, 400 parts of earthworm, 266.7 parts of angelica root, 333.3 parts of belamcanda rhizome, 400 parts of coltsfoot flower, 266.7 parts of prepared pinellia tuber, and 200 parts of licorice root.

3. The application according to any one of claims 1-2, characterized in that, The drug also includes pharmaceutically acceptable excipients.

4. The application according to claim 3, characterized in that, The drugs are selected from decoctions, granules, capsules, tablets, pills, oral liquids, tinctures, syrups, suppositories, gels, sprays, and injections.

5. The application according to any one of claims 1-2, characterized in that, The preparation of the traditional Chinese medicine composition includes: a. Take five medicinal materials: honey-processed ephedra, bitter almond, perilla seed, prepared pinellia, and licorice. Add 10 times the amount of water and decoct three times, 1.5 hours each time. Filter the decoction, concentrate the filtrate under reduced pressure, cool to room temperature, and precipitate with alcohol. Gradually increase the ethanol concentration of the extract concentrate to 75% in a gradient manner, and let it stand for 24 hours. Take the supernatant of the alcohol precipitation and concentrate it under reduced pressure. b. Take five medicinal materials: Scutellaria baicalensis, Peucedanum praeruptorum, Belamcanda chinensis, Tussilago farfara, and Morus alba root bark. Add 8 times the amount of 70% ethanol and reflux extract twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure. c. Take cicada molting, silkworm pupa, and earthworm, add 8 times the amount of water and decoct twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure. Combine the above concentrates, concentrate under reduced pressure, and dry.

6. The application according to any one of claims 1-2, characterized in that, The drug is selected from granules, and the preparation of the granules includes the following steps: a. Take five medicinal materials: honey-processed ephedra, bitter almond, perilla seed, prepared pinellia, and licorice. Add 10 times the amount of water and decoct three times, 1.5 hours each time. Filter the decoction and concentrate the filtrate under reduced pressure to a relative density of 1.08-1.

10. Cool to room temperature and precipitate with alcohol. Gradually increase the ethanol concentration of the extract concentrate to 75% in a gradient manner. Let it stand for 24 hours. Take the supernatant of the alcohol precipitation and concentrate it under reduced pressure to a relative density of 1.10-1.

12. b. Take five medicinal materials: Scutellaria baicalensis, Peucedanum praeruptorum, Belamcanda chinensis, Tussilago farfara, and Morus alba root bark. Add 8 times the amount of 70% ethanol and reflux extract twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure until there is no alcohol taste. c. Take cicada molting, silkworm pupa, and earthworm, add 8 times the amount of water and decoct twice, 1.5 hours each time. Filter and concentrate the filtrate under reduced pressure to a relative density of 1.10-1.

12. Combine the above concentrates and concentrate under reduced pressure to an extract with a relative density of 1.25-1.

27. Dry and pulverize to obtain the intermediate of the traditional Chinese medicine composition. Add dextrin and aspartame, mix evenly, wet granulate, boil dry, and make into granules.

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