A traditional Chinese medicine composition for treating oral diseases and its preparation method

Abstract

This invention relates to a traditional Chinese medicine composition for treating oral diseases and its preparation method, belonging to the field of traditional Chinese medicine technology. The traditional Chinese medicine composition for treating oral diseases is composed of *Clerodendrum trichotomum* and *Radix Araliae*. This invention discovers that the combined use of *Clerodendrum trichotomum* and *Radix Araliae*, with their synergistic effect, significantly improves the therapeutic effect of the resulting composition on oral diseases such as oral ulcers. This not only broadens the application range of *Clerodendrum trichotomum* and *Radix Araliae*, but also provides a new approach to the treatment of oral diseases.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating oral diseases and its preparation method. Background Technology

[0002] Oral health is susceptible to pathological changes caused by external physical and chemical factors, pathogen invasion, dentofacial developmental abnormalities, and systemic diseases. These conditions lead to oral diseases, which are numerous and include conditions such as oral ulcers, bleeding gums, gingivitis, periodontitis, gingival recession, and bone loss. Poor oral health not only causes suffering from these oral diseases but can also trigger other systemic diseases, such as respiratory illnesses. Therefore, the treatment and prevention of oral diseases are of paramount importance to overall health.

[0003] Flavic hyacinth, or wall hyacinth, is the dried thallus of *Theloschestes flavicans* (Sw.) Norm, a plant belonging to the family Chrysanthemataceae. It is obtained by harvesting, removing soil, and sun-drying. This medicine is listed in the *Drug Standards of the Ministry of Health of the People's Republic of China*, specifically in the section on Tibetan medicine (Volume 1). It is cool in nature and bitter in taste. It has the effects of clearing heat and detoxifying, and can be used to treat symptoms such as lung heat, liver heat, pulse heat, and toxic heat.

[0004] *Campylotropis trigonoclada* (Franch.) AKSchindl., a plant belonging to the genus *Campylotropis* in the family Fabaceae, is used medicinally for its roots and whole plant. It has a pungent, slightly sweet, and astringent taste, is non-toxic, and neutral in nature. It enters the liver, large intestine, and heart meridians, and possesses the effects of cooling the blood, clearing heat, and detoxifying. Clinically, it is mainly used to treat colds with fever, rheumatoid arthritis, and other diseases.

[0005] Currently, there are many types of oral disease treatments on the market, but there are no reports of combining wall coverings and large-leaved paper in the preparation of oral disease treatment products in existing technologies. Summary of the Invention

[0006] To address the above problems, this invention provides a traditional Chinese medicine composition for treating oral diseases and its preparation method.

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating oral diseases, the traditional Chinese medicine composition for treating oral diseases being composed of *Clerodendrum trichotomum* and *Artemisia capillaris*.

[0008] Furthermore, the traditional Chinese medicine composition for treating oral diseases, by weight, comprises the following raw materials:

[0009] 15-35 pieces of wall coverings and 4-9 pieces of large foliage.

[0010] Furthermore, the traditional Chinese medicine composition for treating oral diseases, by weight, comprises the following raw materials:

[0011] 31 wall coverings and 6 large prints.

[0012] Furthermore, the oral diseases include oral ulcers.

[0013] In a second aspect, the present invention provides a method for preparing the traditional Chinese medicine composition for treating oral diseases according to any one of the first aspects, the preparation method comprising the following steps:

[0014] The wall covering was pulverized and subjected to a first reflux extraction using petroleum ether as the first extraction solvent. The resulting first extract was then concentrated and dried to obtain the wall covering extract.

[0015] The large-leaved oyster shell was crushed and subjected to a second reflux extraction using 95% ethanol as the second extraction solvent. The resulting second extract was then concentrated to obtain a paste.

[0016] The extract was subjected to gradient elution on a D101 macroporous resin column. First, water was used for elution, followed by 45%–65% ethanol by volume. The ethanol eluents at different volume fractions were collected, concentrated, and dried to obtain the macroporous extract.

[0017] The herbal composition is obtained by mixing the lichen extract and the sesame extract.

[0018] Furthermore, the operating parameters of the first reflux extraction include: an extraction temperature of 95–115°C, an extraction time of 1–2 hours, and a weight ratio of the wall coating to the first extraction solvent of 1:(5–12).

[0019] Furthermore, the operating parameters for the second reflux extraction include: an extraction temperature of 85–100°C, an extraction time of 1.5–3 hours, and a weight ratio of the large amount of styrax to the second extraction solvent of 1:(5–12).

[0020] Further, the extract is subjected to gradient elution on a D101 macroporous resin column, first eluted with water, then eluted with 45%–65% ethanol (v / v). The ethanol eluates at different v / v fractions are collected, concentrated, and dried to obtain the large-volume extract. The steps include the following:

[0021] The extract was mixed with D101 macroporous resin at a weight ratio of 1:1 and then loaded onto a column using a dry method. The mixture was first eluted with 3 to 6 column volumes of water, followed by gradient elution with 45% ethanol, 55% ethanol, and 65% ethanol, with each gradient eluent being 5 to 15 column volumes. The eluents of 45% ethanol, 55% ethanol, and 65% ethanol were collected, concentrated, and dried to obtain the macroporous extract.

[0022] The technical solution provided by this invention has at least the following advantages compared with the prior art:

[0023] This invention provides a traditional Chinese medicine composition for treating oral diseases. The invention discovers that the combined use of *Clerodendrum trichotomum* and *Radix Araliae* synergistically enhances the therapeutic effect of the resulting composition on oral diseases such as oral ulcers. This not only broadens the application scope of *Clerodendrum trichotomum* and *Radix Araliae* synergistically, but also provides a new approach to the treatment of oral diseases. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0025] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0026] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating oral diseases, the traditional Chinese medicine composition for treating oral diseases being composed of *Clerodendrum trichotomum* and *Artemisia capillaris*.

[0027] This invention provides a traditional Chinese medicine composition for treating oral diseases. The invention discovers that the combined use of *Clerodendrum trichotomum* and *Radix Araliae* synergistically enhances the therapeutic effect of the resulting composition on oral diseases such as oral ulcers. This not only broadens the application scope of *Clerodendrum trichotomum* and *Radix Araliae* synergistically, but also provides a new approach to the treatment of oral diseases.

[0028] In some specific embodiments, the traditional Chinese medicine composition for treating oral diseases, by weight, comprises the following raw materials:

[0029] 15-35 pieces of wall coverings and 4-9 pieces of large foliage.

[0030] In some specific embodiments, the traditional Chinese medicine composition for treating oral diseases, by weight, comprises the following raw materials:

[0031] 31 wall coverings and 6 large prints.

[0032] In some specific embodiments, the oral disease includes oral ulcers.

[0033] It should be noted that, unless otherwise specified or indicated, the raw materials involved in the traditional Chinese medicine composition for treating oral diseases provided by this invention can be directly derived from commercially available products or prepared in-house using existing processes.

[0034] Secondly, based on a general inventive concept, the present invention provides a method for preparing a traditional Chinese medicine composition for treating oral diseases as described in any of the first aspects, the preparation method comprising the following steps:

[0035] The wall covering was pulverized and subjected to a first reflux extraction using petroleum ether as the first extraction solvent. The resulting first extract was then concentrated and dried to obtain the wall covering extract.

[0036] The large-leaved oyster shell was crushed and subjected to a second reflux extraction using 95% ethanol as the second extraction solvent. The resulting second extract was then concentrated to obtain a paste.

[0037] The extract was subjected to gradient elution on a D101 macroporous resin column. First, water was used for elution, followed by 45%–65% ethanol by volume. The ethanol eluents at different volume fractions were collected, concentrated, and dried to obtain the macroporous extract.

[0038] The herbal composition is obtained by mixing the lichen extract and the sesame extract.

[0039] The method for preparing the traditional Chinese medicine composition for treating oral diseases provided by this invention is simple to operate, requires no additional specific equipment, and is suitable for mass industrial production.

[0040] In some specific embodiments, the operating parameters of the first reflux extraction include: an extraction temperature of 95-115°C, an extraction time of 1-2 hours, and a weight ratio of the wall coating to the first extraction solvent of 1:(5-12).

[0041] In some specific embodiments, the boiling point of the petroleum ether is 90–100°C.

[0042] In some specific embodiments, the operating parameters of the second reflux extraction include: an extraction temperature of 85–100°C, an extraction time of 1.5–3 hours, and a weight ratio of the large amount of styrax to the second extraction solvent of 1:(5–12).

[0043] In some specific embodiments, the extract is subjected to gradient elution on a D101 macroporous resin column, first eluted with water, then eluted with 45%–65% ethanol (v / v), and the ethanol eluates at different v / v fractions are collected, concentrated, and dried to obtain the large-leaf extract. The steps include the following:

[0044] The extract was mixed with D101 macroporous resin at a weight ratio of 1:1 and then loaded onto a column using a dry method. The mixture was first eluted with 3 to 6 column volumes of water, followed by gradient elution with 45% ethanol, 55% ethanol, and 65% ethanol, with each gradient eluent being 5 to 15 column volumes. The eluents of 45% ethanol, 55% ethanol, and 65% ethanol were collected, concentrated, and dried to obtain the macroporous extract.

[0045] In some specific embodiments, the relative density of the extract may be 1.1 to 1.3.

[0046] It should be noted that, unless otherwise specified or described, the operational steps involved in the traditional Chinese medicine composition for treating oral diseases provided by this invention can be carried out in accordance with existing traditional Chinese medicine extract preparation processes or using existing equipment, and will not be described in detail here.

[0047] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed according to national standards. If no corresponding national standard exists, then generally accepted international standards, conventional conditions, or conditions recommended by the manufacturer are followed.

[0048] Example 1

[0049] This example provides a traditional Chinese medicine composition for treating oral diseases, which, by weight, consists of the following raw materials: 31 parts of wall covering and 6 parts of large-leaved oyster shell.

[0050] The preparation method of the above-mentioned traditional Chinese medicine composition for treating oral diseases includes the following steps:

[0051] Step (1): The wall covering is crushed and refluxed with petroleum ether as the first extraction solvent. The extraction temperature is 105℃ and the extraction time is 1.5 hours. The weight ratio of the wall covering to the first extraction solvent is 1:8. The extraction is performed twice. The first extract is then concentrated and dried to obtain the wall covering extract.

[0052] Step (2): The large-sized oyster shell is crushed and subjected to a second reflux extraction using 95% ethanol as the second extraction solvent. The extraction temperature is 95℃ and the extraction time is 2 hours. The weight ratio of the large-sized oyster shell to the second extraction solvent is 1:10. The extraction is performed twice. The resulting second extract is then concentrated to obtain an extract.

[0053] Step (3): Mix the extract obtained in step (2) with D101 macroporous resin at a weight ratio of 1:1, dry load the mixture onto a column, first elute with 5 column volumes of water, then elute sequentially with 45% ethanol, 55% ethanol and 65% ethanol, with each eluent being 12 column volumes. Collect the eluents of 45% ethanol, 55% ethanol and 65% ethanol and concentrate and dry them to obtain the macroporous extract.

[0054] Step (4): Mix the crease extract obtained in step (1) and the oyster extract obtained in step (3) to obtain the traditional Chinese medicine composition for treating oral diseases.

[0055] Example 2

[0056] This example provides a traditional Chinese medicine composition for treating oral diseases and its preparation method. The only difference from Example 1 is that, by weight, the traditional Chinese medicine composition for treating oral diseases consists of the following raw materials: 15 parts of wall covering and 4 parts of large-leaved scallion; the remaining steps and parameters are the same.

[0057] Example 3

[0058] This example provides a traditional Chinese medicine composition for treating oral diseases and its preparation method. The only difference from Example 1 is that, by weight, the traditional Chinese medicine composition for treating oral diseases consists of the following raw materials: 35 parts of wall covering and 9 parts of large-leaved scallion; the remaining steps and parameters are the same.

[0059] Comparative Example 1

[0060] This example provides a traditional Chinese medicine composition for treating oral diseases, which differs from Example 1 only in that the first extraction solvent in step (1) is changed to water; the remaining steps and parameters are the same.

[0061] Comparative Example 2

[0062] This example provides a traditional Chinese medicine composition for treating oral diseases. The only difference from Example 1 is that the solvent for gradient elution in step (3) is adjusted to have a volume fraction of 75% ethanol, 85% ethanol, and 95% ethanol. The eluent of 75% ethanol, 85% ethanol, and 95% ethanol is then collected, concentrated, and dried to obtain the large-scale extract. The remaining steps and parameters are the same.

[0063] The preparation method of the above-mentioned traditional Chinese medicine composition for treating oral diseases includes the following steps:

[0064] Step (1): The wall covering is crushed and refluxed with petroleum ether as the first extraction solvent. The extraction temperature is 105℃ and the extraction time is 1.5 hours. The weight ratio of the wall covering to the first extraction solvent is 1:8. The extraction is performed twice. The first extract is then concentrated and dried to obtain the wall covering extract.

[0065] Step (2): The large-sized oyster shell is crushed and subjected to a second reflux extraction using 95% ethanol as the second extraction solvent. The extraction temperature is 95℃ and the extraction time is 2 hours. The weight ratio of the large-sized oyster shell to the second extraction solvent is 1:10. The extraction is performed twice. The resulting second extract is then concentrated to obtain an extract.

[0066] Step (3): Mix the extract obtained in step (2) with D101 macroporous resin at a weight ratio of 1:1, dry load the mixture onto a column, elute with 5 column volumes of water, and then elute sequentially with 75% ethanol, 85% ethanol and 95% ethanol, with each eluent being 12 column volumes. Collect the eluents of 75% ethanol, 85% ethanol and 95% ethanol and concentrate and dry them to obtain the macroporous extract.

[0067] Step (4): Mix the crease extract obtained in step (1) and the oyster extract obtained in step (3) to obtain the traditional Chinese medicine composition for treating oral diseases.

[0068] Comparative Example 3

[0069] This example provides a traditional Chinese medicine composition for treating oral diseases, which differs from Example 1 only in that the dosage of Da Fa is adjusted to 25 parts; all other steps and parameters are the same.

[0070] Test case

[0071] This example tests the efficacy of the traditional Chinese medicine composition for treating oral diseases provided in the examples and comparative examples, the lichen extract obtained in step (1) of Example 1, and the daisy extract obtained in step (3).

[0072] Test method: Kunming mice, half male and half female, weighing 18-22 grams, were randomly divided into 9 groups: 1 model control group and 8 treatment groups, with 10 mice in each group. An animal model of oral ulcers was established using the chemical cauterization method reported in existing technology. Mice were anesthetized with 1% sodium pentobarbital (0.025 g / kg), and NaOH solid was used to cauterize the mucosa near the corner of the mouth on the lower lip for 5 seconds. The ulcers were rinsed with physiological saline, and ulcers formed one day later. The size of the ulcers in each animal was recorded. The model was established in the same location as possible for each animal, with consistent size and depth. All mice in each group had free access to water and chow pellets. The 8 treatment groups were given the traditional Chinese medicine composition for treating oral diseases provided in Examples 1-3 and Comparative Examples 1-3, the lichen extract obtained in step (1) of Example 1, and the oyster extract obtained in step (3), respectively, at a dosage of 0.02 g / g (dose / body weight), administered by gavage twice daily (morning and evening). The model control group was given the same volume of physiological saline daily. The drug was administered continuously for one week, and the changes in ulcers were recorded daily. The test data results were statistically analyzed.

[0073] Test results showed that the ulcer area was basically the same in all groups of mice at the time of modeling. After treatment, the ulcers in the first-instance groups were almost completely healed, while those in the other test groups were not completely healed. The ulcer area (mm²) on day 0 of treatment (i.e., before treatment began after modeling) and day 3 of treatment were also measured. 2 The test data results (expressed as mean ± standard deviation) are shown in Table 1.

[0074] Table 1

[0075] Group Day 0 of treatment 3 days after treatment Model control group 5.37±1.35 5.34±1.29 Wall lily extract group 5.48±1.43 4.56±1.30 Large-scale extract group 5.32±1.41 4.84±1.46 Example 1 Group 5.59±1.38 2.68±1.07 Example 2 group 5.45±1.47 3.51±1.24 Example 3 Group 5.50±1.40 3.46±1.18 Comparative Example 1 5.35±1.32 4.33±1.25 Comparative Example 2 5.30±1.45 4.14±1.26 Comparative Example 3 Groups 5.28±1.39 4.07±1.22

[0076] As shown in Table 1:

[0077] 1) Compared to the lichen extract group and the oyster extract group, the ulcer area in mice treated for 3 days in Example 1 of this invention was significantly reduced. This indicates that by using lichen and oyster extract in combination, the two work synergistically to significantly improve the therapeutic effect of the resulting composition on oral ulcers.

[0078] 2) Compared to Comparative Example 3, the compositions provided in Examples 1-3 of this invention showed a more significant effect in reducing the ulcer area in mice. This indicates that the dosage of Dafabet in the compositions provided by this invention should not be excessive, otherwise the two drugs will exhibit a certain degree of antagonism.

[0079] 3) Compared with the test results of Comparative Example 1, Comparative Example 2 and Example 1, it shows that the composition obtained by preferentially using the petroleum ether extract of the wall covering and eluting with 45% to 65% ethanol under a specific gradient has a better therapeutic effect on oral ulcers.

[0080] In addition, this example refers to the YY / T0127.13-2009 pharmaceutical industry standard to conduct an oral mucosal irritation test on the composition provided in the embodiment of the present invention. The test results show that the composition provided in the embodiment of the present invention has a reaction grade of 0 on oral mucosal tissue, that is, no tissue irritation reaction, and can be further applied to the preparation of oral care products.

[0081] In summary, this invention provides a traditional Chinese medicine composition for treating oral diseases. This invention discovers that the combined use of *Clerodendrum trichotomum* and *Radix Araliae* synergistically enhances the therapeutic effect of the resulting composition on oral diseases such as oral ulcers. This not only broadens the application scope of *Clerodendrum trichotomum* and *Radix Araliae* synergistically, but also provides a new approach to the treatment of oral diseases.

[0082] The above description is merely a specific embodiment of the present invention, enabling those skilled in the art to understand or implement the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A traditional Chinese medicine composition for treating oral diseases, characterized in that, The traditional Chinese medicine composition for treating oral diseases is made of the following raw materials in parts by weight: The traditional Chinese medicine composition for treating oral diseases is made of the following raw materials in parts by weight: The traditional Chinese medicine composition for treating oral diseases is made of the following raw materials in parts by weight: The preparation method of the traditional Chinese medicine composition for treating oral diseases comprises the following steps: The wall clothes is crushed and first reflux extraction is carried out with petroleum ether as the first extraction solvent, and then the obtained first extraction liquid is concentrated and dried to obtain wall clothes extract; The Dahuabai is crushed and second reflux extraction is carried out with 95% ethanol by volume fraction as the second extraction solvent, and then the obtained second extraction liquid is concentrated to obtain extract; The extract and D101 macroporous resin are mixed uniformly according to a weight ratio of 1:1, dry column is used, 3-6 times the column volume of water is used for elution, and then 45% ethanol, 55% ethanol and 65% ethanol by volume fraction are used for gradient elution in sequence, the use amount of each gradient eluent is 5-15 times the column volume, and the eluents of 45% ethanol, 55% ethanol and 65% ethanol are collected and concentrated and dried to obtain Dahuabai extract; 2. The traditional Chinese medicine composition for treating oral diseases according to claim 1, characterized in that, The wall clothes extract and the Dahuabai extract are mixed to obtain the traditional Chinese medicine composition. The traditional Chinese medicine composition for treating oral diseases is made of the following raw materials in parts by weight:

3. The traditional Chinese medicine composition for treating oral diseases according to claim 1, characterized in that, Wall clothes 31 parts and Dahuabai 6 parts.

4. The traditional Chinese medicine composition for treating oral diseases according to claim 1, characterized in that, The working parameters of the first reflux extraction include that the extraction temperature is 95-115°C, the extraction time is 1-2 hours, and the weight ratio of the wall clothes to the first extraction solvent is 1:(5-12). The working parameters of the second reflux extraction include that the extraction temperature is 85-100°C, the extraction time is 1.5-3 hours, and the weight ratio of the Dahuabai to the second extraction solvent is 1:(5-12).