A traditional Chinese medicine oral cavity bacteriostatic smearing paste as well as a preparation method and application thereof

Abstract

The present application is prepared by the combination of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract and forsythia suspense extract, and is a kind of traditional Chinese medicine oral cavity bacteriostatic paste, which can resist more than 95% of oral bacteria, can also freshen breath for a long time, and can be used by pregnant women and children. It has the effects of preventing and treating oral ulcer, treating gum swelling and pain, repairing teeth, removing dental plaque, dental calculus, protecting gum and oral mucosa, inhibiting and treating tongue cancer cells.

Description

Technical fields:

[0001] This invention belongs to the field of traditional Chinese medicine development technology, specifically relating to a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application. Background Technology

[0002] Oral diseases are pathological phenomena originating in the oral cavity. The main causes include damage from physical and chemical factors, pathogen infection, dentofacial developmental abnormalities, and systemic diseases. According to the book *Oral Diseases*, these diseases encompass dental caries, periodontal disease, oral mucosal lesions, and oral cancer. Periodontal disease has a prevalence rate as high as 62.4% among adults in my country. The Fourth National Oral Health Epidemiological Survey showed that less than 10% of adults in my country have healthy periodontiums. In 2021, the major oral diseases worldwide included untreated dental caries, severe periodontitis, edentulism, oral ulcers caused by pathogens, and other oral diseases, with an age-standardized overall prevalence of 45,900 cases per 100,000 people.

[0003] When people eat, food residue inevitably remains in their mouths. Neglecting oral hygiene for a long time can lead to the growth of bacteria in the mouth, which can seriously cause oral ulcers. Bacteria such as Staphylococcus aureus, Helicobacter pylori, and Streptococcus mutans can not only induce oral diseases such as tooth decay, gingivitis, and periodontitis, but also promote the growth of anaerobic bacteria, which in turn produce sulfides, resulting in bad breath.

[0004] Chinese Patent CN116602900A discloses a "Dang Gui Chinese Medicine Oral Antibacterial Paste and its Preparation Method". The toothpaste, prepared with angelica extract and paeonol as the main raw materials, has the functions of cleaning teeth, protecting gums, removing dental plaque and stains, and freshening breath.

[0005] Chinese patent CN115350116A discloses a "traditional Chinese medicine oral antibacterial ointment and its preparation method and application", which is an ointment with strong bactericidal effect against Enterococcus faecalis prepared from materials such as curcumin and asiaticoside.

[0006] Chinese patent CN105769924A discloses a "propolis-based oral antibacterial ointment and its preparation method," which has the beneficial effects of regulating, caring for, and antibacterial the teeth and gums, thus restoring dental health.

[0007] Chinese patent CN2014100693322.5 discloses an "oral fungal antibacterial agent" that has strong antibacterial activity against fungi such as Candida albicans and has a good therapeutic effect on patients with oral fungal infections.

[0008] The aforementioned Chinese invention patents have drawbacks such as short drug retention time in the oral cavity, low bioavailability, poor antibacterial effect, and long treatment time. Summary of the Invention

[0009] To address the shortcomings of existing technologies, this invention creatively combines extracts of dragon's blood, artemisia annua, honeysuckle, licorice, and forsythia to prepare a "traditional Chinese medicine oral antibacterial ointment." This ointment can combat over 95% of oral bacteria, provide long-lasting fresh breath, and is suitable for pregnant women and children. While inhibiting and killing bacteria, it also repairs teeth, removes plaque and tartar, protects gums and oral mucosa, and prevents and treats oral ulcers, swollen and painful gums, and periodontitis.

[0010] This invention features high bioavailability, rapid onset of action, and fast absorption; it has no first-pass effect and no toxic side effects. Furthermore, Pharmacological studies have shown that this invention can also alleviate and treat tongue cancer. Therefore, it has a more significant meaning.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is: a "traditional Chinese medicine oral antibacterial ointment" and its preparation method and application, which is composed of active pharmaceutical ingredients and excipients.

[0012] The active pharmaceutical ingredient is composed of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract.

[0013] The Dragon's Blood Extract It possesses the effects of promoting blood circulation and removing blood stasis, relieving pain and stopping bleeding, and promoting tissue regeneration. Clinically, it is suitable for treating injuries from falls and blows, pain due to blood stasis, stagnation of qi and blood in women, external bleeding, slow-healing abscesses, and abdominal pain and diarrhea caused by chronic colitis. Existing research data shows that dragon's blood extract can also be used to improve kidney function, treat non-alcoholic fatty liver disease, and improve blood rheology.

[0014] The Artemisia annua extract It is an active ingredient extracted from the plant Artemisia annua, and its main effects include antimalarial, anti-inflammatory, immunomodulatory, antioxidant, antiviral, tumor growth inhibition, and other antioxidant properties.

[0015] The Honeysuckle extract This is a natural product extracted from the dried buds or newly opened flowers of *Lonicera japonica*, a plant in the Caprifoliaceae family. It possesses antibacterial, anti-inflammatory, and antioxidant properties. Modern research has confirmed its significant antibacterial activity against Streptococcus, Staphylococcus, and Escherichia coli. The honeysuckle extract prepared in this invention utilizes supercritical fluid extraction technology combined with ultra-low temperature freeze-drying, which effectively preserves active ingredients such as chlorogenic acid.

[0016] The Licorice extract, It is a medicinal component extracted from licorice, which has the effects of tonifying the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, relieving spasms and pain, and harmonizing various medicines.

[0017] The Forsythia extract, It is an active ingredient extracted from the dried fruit of Forsythia suspensa, a plant in the Oleaceae family. It has antibacterial, anti-inflammatory, and antioxidant effects and is used for wind-heat colds, sore throats, and respiratory infections.

[0018] The "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared by this invention comprises, by weight percentage, the following active pharmaceutical ingredients: Dragon's Blood Extract: Artemisia annua Extract: Honeysuckle Extract: Licorice Extract: Forsythia Extract, each comprising 1-2%, 1.5-2%, 1-3%, 0.5-1.5%, and 0.5-1.5%, respectively.

[0019] The active pharmaceutical ingredient, calculated by weight percentage, may also be: Dragon's Blood Extract: Artemisia annua Extract: Honeysuckle Extract: Licorice Extract: Forsythia Extract, respectively, in the following proportions: 1.0%: 1.5%: 1.0%: 0.5%: 0.5%.

[0020] The active pharmaceutical ingredient, calculated by weight percentage, may also be 2.0% for Dragon's Blood Extract, 2.0% for Artemisia annua Extract, 3.0% for Lonicera japonica Extract, 1.5% for Glycyrrhiza uralensis Extract, and 1.5% for Forsythia suspensa Extract, respectively.

[0021] The active pharmaceutical ingredient, calculated by weight percentage, may also be 1.5% for Dragon's Blood Extract, 1.7% for Artemisia annua Extract, 1.7% for Honeysuckle Extract, 1.0% for Licorice Extract, and 0.8% for Forsythia Extract.

[0022] The active pharmaceutical ingredient, calculated by weight percentage, may also be 1.8% for Dragon's Blood Extract, 1.5% for Artemisia annua Extract, 1.0% for Honeysuckle Extract, 1.5% for Licorice Extract, and 1.3% for Forsythia Extract.

[0023] The active pharmaceutical ingredient, calculated by weight percentage, may also be 1.6% for Dragon's Blood Extract, 2.0% for Artemisia annua Extract, 1.5% for Honeysuckle Extract, 1.2% for Licorice Extract, and 1.3% for Forsythia Extract.

[0024] The active pharmaceutical ingredient, calculated by weight percentage, may also be 1.5% for Dragon's Blood Extract, 1.8% for Artemisia annua Extract, 1.3% for Honeysuckle Extract, 1.4% for Licorice Extract, and 1.4% for Forsythia Extract.

[0025] Preferably, the active pharmaceutical ingredients, calculated by weight percentage, are: Dragon's Blood Extract: Artemisia annua Extract: Honeysuckle Extract: Licorice Extract: Forsythia Extract, which are 2.0%, 1.8%, 2.0%, 1.0%, and 1.0% respectively.

[0026] The excipients include thickeners, anionic surfactants, softeners, sweeteners, preservatives, and water. The thickeners include, but are not limited to, sodium carboxymethyl cellulose (CMC), hydroxyethyl cellulose, carbomer resin, xanthan gum, polyethylene glycol 400, polyethylene glycol 150, polyethylene glycol 2000, modified guar gum, and carrageenan, with xanthan gum and polyethylene glycol 400 being preferred.

[0027] The anionic surfactant (which is also a transdermal absorption enhancer) includes, but is not limited to, one or more of sulfosuccinate, sodium lauryl sulfate, and sodium lauroyl sarcosinate, preferably sodium lauryl sulfate and sodium lauroyl sarcosinate.

[0028] The softener includes, but is not limited to, glycerin, diethylaminoethanol, triethanolamine, and oleyl alcohol polyoxyethylene ether, with glycerin being preferred.

[0029] The sweeteners include, but are not limited to, sucrose, steviol, glycerin, sorbitol, and mannitol, with sorbitol being preferred.

[0030] The invention of "a traditional Chinese medicine oral antibacterial ointment" was chosen because, during the formulation research, the inventors, considering the drug's release mechanism and pharmacological effects, prioritized the preparation of a traditional Chinese medicine oral antibacterial ointment. This is mainly because the drug of this invention uses surfactants (which are also transdermal absorption enhancers) and other excipients as carriers in the oral cavity. When applied to the affected area, the drug has a long retention time in the oral cavity. Utilizing the strong permeability of the oral mucosa, the drug is absorbed quickly and has high bioavailability. It avoids the first-pass effect of the liver and the enzymatic and acidic hydrolysis in the gastrointestinal tract, resulting in no first-pass effect and no toxic side effects. Therefore, choosing the traditional Chinese medicine oral antibacterial ointment as the formulation is of significant importance.

[0031] Furthermore, during the research process of this invention, the inventors used it on two patients with tongue cancer, and the cancer of the tongue cancer patients... The inventors then conducted pharmacodynamic experiments to study the lack of cell proliferation and growth, which resulted in tumor shrinkage, proving the effectiveness of their invention. The invention demonstrates an inhibitory effect on tongue cancer cells (see Experimental Example 5). The "Traditional Chinese Medicine Oral Antibacterial Ointment" of this invention is now being used in clinical trials for tongue cancer. In the experiment.

[0032] This invention, "A Traditional Chinese Medicine Oral Antibacterial Ointment, Its Preparation Method and Application," is characterized by:

[0033] (1) Dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract and forsythia extract were pulverized by ultra-high-powered pulverizer and passed through a 350-mesh sieve, which increased the surface area of ​​the drugs and improved their bioavailability.

[0034] (2) Pharmacological experiments show that each 100g of antibacterial ointment contains 1-2% dragon's blood extract, 1.5-2% artemisia annua extract, 1-3% honeysuckle extract, 0.5-1.5% licorice extract, and 0.5-1.5% forsythia extract. Preferably, each 100g of antibacterial ointment contains 2.0% dragon's blood extract, 1.8% artemisia annua extract, 2.0% honeysuckle extract, 1.0% licorice extract, and 1.0% forsythia extract.

[0035] (3) The “Chinese medicine oral antibacterial ointment” prepared by the present invention is used in doses of 0.5 to 2.0g each time, preferably 1.0g.

[0036] (4) The method of using the "Chinese medicine oral antibacterial ointment" prepared in this invention is to apply the "Chinese medicine oral antibacterial ointment" of this invention to the affected area for 5-10 minutes, and then drink water or eat food.

[0037] (5) The present invention provides a traditional Chinese medicine oral antibacterial ointment, which has the functions of preventing and treating oral ulcers, treating gingival swelling and pain, repairing teeth, removing dental plaque and tartar, and protecting the gums and oral mucosa. Relief and treatment of tongue cancer and It has effects such as relieving bad breath.

[0038] (6) The "Chinese medicine oral antibacterial ointment" prepared by the present invention has no toxic side effects. Dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract can also be added to common excipients such as diluents and excipients to prepare other oral preparations, such as pills, mixtures, tablets, capsules, granules, oral lozenges, and can also be prepared into aerosols, sprays, and medicated toothpastes.

[0039] Beneficial effects

[0040] This invention creatively combines extracts of dragon's blood, artemisia annua, honeysuckle, licorice, and forsythia to prepare a "traditional Chinese medicine oral antibacterial ointment." This is because the drugs are pulverized using ultra-high-performance pulverizers to achieve small particle sizes. Utilizing surfactants (which are also transdermal absorption enhancers) as carriers, and after emulsification and homogenization, the drug has a large dispersion area in the oral cavity. This results in greater and faster absorption of the drug through the oral and sublingual mucosa within a certain timeframe. Furthermore, the drug can be absorbed directly into the systemic circulation via the oral mucosa and sublingual veins, bypassing the liver, without first-pass effect or toxic side effects. pharmacological experiments Studies have shown that it may also alleviate and treat tongue cancer. Therefore, it has a more significant meaning. Detailed Implementation

[0041] The present invention will be further illustrated by some specific embodiments below, but the embodiments do not limit the present invention in any way unless otherwise stated.

[0042] Example 1

[0043] The preparation steps for "A Traditional Chinese Medicine Oral Antibacterial Ointment, Its Preparation Method and Application" are as follows:

[0044] 1. Prescription:

[0045] Prepare 1000g

[0046] Phase A: Dragon's Blood Extract 2.0%, Artemisia annua Extract 1.8%, Honeysuckle Extract 2.0%, Licorice Extract 1.0%, Forsythia Extract 1.0%, Sodium Lauryl Sulfate 2.0%, Sodium Lauroyl Sarcosinate 1.5%, Xanthan Gum 30%, Glycerin 45%, Water as needed;

[0047] Phase B: Sorbitol 2.0%, Polyethylene Glycol 400 10%, Eugenol 1%;

[0048] Phase C: Sodium benzoate 0.5%.

[0049] 2. Preparation method:

[0050] 2.1 Add an appropriate amount of water to the emulsification pot. While stirring at 10-20 r / min, slowly add the extracts of dragon's blood, artemisia annua, honeysuckle, licorice, and forsythia. After they are completely soaked, start stirring at 30-50 r / min until they are completely dissolved. Then add the other raw materials in phase A. Heat to 80°C and emulsify at 2000-2500 r / min. Stop stirring when the temperature drops to 50-60°C to obtain phase A solution.

[0051] 2.2 Slowly add phase B raw material to phase A solution and continue stirring for 45-60 minutes until the solution is homogeneous to obtain phase B solution;

[0052] 2.3 Add sodium benzoate from phase C to phase B, add water to 1000g, start stirring at 30-50r / min until the solution is homogeneous, then stop stirring to obtain phase C solution;

[0053] 2.4 The C-phase solution was degassed under vacuum to eliminate air bubbles, resulting in a traditional Chinese medicine oral antibacterial ointment;

[0054] 2.5 Fill the above-mentioned Chinese herbal oral antibacterial ointment into a clean and sterile container, seal it, protect it from light, and refrigerate it to obtain the product.

[0055] Example 2

[0056] The preparation steps for "A Traditional Chinese Medicine Oral Antibacterial Ointment, Its Preparation Method and Application" are as follows:

[0057] 1. Prescription:

[0058] Prepare 1000g

[0059] Phase A: Dragon's Blood Extract 1.0%, Artemisia annua Extract 1.5%, Honeysuckle Extract 1.0%, Licorice Extract 0.5%, Forsythia Extract 0.5%, Sodium Lauryl Sulfate 5.0%, Sodium Lauroyl Sarcosinate 3.5%, Xanthan Gum 10%, Glycerin 50%, Water as needed;

[0060] Phase B: Sorbitol 0.5%, polyethylene glycol 400 5%, eugenol 1.5%;

[0061] Phase C: Sodium benzoate 1.5%.

[0062] 2. Preparation method: Same as in Example 1

[0063] Example 3

[0064] The preparation steps for "A Traditional Chinese Medicine Oral Antibacterial Ointment, Its Preparation Method and Application" are as follows:

[0065] 1. Prescription:

[0066] Prepare 1000g

[0067] Phase A: Dragon's Blood Extract 1.5%, Artemisia annua Extract 1.7%, Honeysuckle Extract 1.7%, Licorice Extract 1.0%, Forsythia Extract 0.8%, Sodium Lauryl Sulfate 7.5%, Sodium Lauroyl Sarcosinate 15%, Xanthan Gum 15%, Glycerin 40%, Water as needed;

[0068] Phase B: Sorbitol 2.0%, polyethylene glycol 400 3%, eugenol 3.5%;

[0069] Phase C: Sodium benzoate 0.5%.

[0070] 2. Preparation method: Same as in Example 1

[0071] Example 4

[0072] The preparation steps for "A Traditional Chinese Medicine Oral Antibacterial Ointment, Its Preparation Method and Application" are as follows:

[0073] 1. Prescription:

[0074] Prepare 1000g

[0075] Phase A: Dragon's Blood Extract 1.0%, Artemisia annua Extract 1.5%, Honeysuckle Extract 1.0%, Licorice Extract 0.5%, Forsythia Extract 0.5%, Sodium Lauryl Sulfate 7.0%, Sodium Lauroyl Sarcosinate 13%, Xanthan Gum 20%, Glycerin 45%, Water as needed;

[0076] Phase B: Sorbitol 2.5%, Polyethylene Glycol 400 2.5%, Eugenol 1.0%;

[0077] Phase C: Sodium benzoate 0.2%.

[0078] 2. Preparation method: Same as in Example 1

[0079] Example 5

[0080] The preparation steps for "A Traditional Chinese Medicine Oral Antibacterial Ointment, Its Preparation Method and Application" are as follows:

[0081] 1. Prescription:

[0082] Prepare 1000g

[0083] Phase A: Dragon's Blood Extract 1.6%, Artemisia annua Extract 2.0%, Honeysuckle Extract 1.5%, Licorice Extract 1.2%, Forsythia Extract 1.3%, Sodium Lauryl Sulfate 7.0%, Sodium Lauroyl Sarcosinate 13%, Xanthan Gum 20%, Glycerin 35%, Water as needed;

[0084] Phase B: Sorbitol 2.5%, Polyethylene Glycol 400 2.5%, Eugenol 4.0%;

[0085] Phase C: Sodium benzoate 0.5%.

[0086] 2. Preparation method: Same as in Example 1

[0087] Experimental Example 1

[0088] The purpose of conducting microbial tests on the traditional Chinese medicine oral antibacterial ointments prepared in Examples 1-5 was to verify whether the "traditional Chinese medicine oral antibacterial ointment" prepared using the present invention meets the national requirements for microbial quality of pharmaceuticals.

[0089] Testing standard: Chinese Pharmacopoeia 2025 edition, Part IV.

[0090] Test results: See Table 1

[0091] Table 1: Microbiological test results of the traditional Chinese medicine oral antibacterial ointment prepared in Examples 1-5 of this invention:

[0092]

[0093]

[0094] The above experimental results show that the oral antibacterial ointment prepared according to Examples 1-5 of the present invention meets the requirements of the Chinese Pharmacopoeia in terms of microorganisms, according to hygienic testing.

[0095] Experimental Example 2

[0096] The bactericidal effect of the traditional Chinese medicine oral antibacterial ointment prepared in Examples 1-5 of this invention was investigated.

[0097] Methods: The "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5 of this invention was tested according to the Microbial Identification Methods of the 2025 Edition of the Chinese Pharmacopoeia, Part IV. Experimental results are shown in Table 2.

[0098] Table 2: Antibacterial effect of the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5 of the present invention.

[0099]

[0100]

[0101] Experimental Results: Table 2 shows that the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5 of this invention has excellent bactericidal and inhibitory effects against Escherichia coli, Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis. In particular, the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Example 1 of this invention has a stronger bactericidal effect than the antibacterial ointments prepared in other examples. It achieved 100% bactericidal effect within 30 minutes.

[0102] The following experimental examples further illustrate the present invention in detail, but the scope of protection of the present invention is not limited by the specific experimental examples, but is defined by the claims.

[0103] Experimental Example 3

[0104] The therapeutic effects of the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5 of this invention on oral mucositis were investigated.

[0105] 1. Evaluation Criteria: Normal oral mucosa should be moist, intact, smooth, and pink in color, without erosion, ulcers, or lumps. Grade 0: No abnormalities in oral mucosa; Grade 1: No more than 2 ulcers smaller than 1.0 cm in the oral cavity, accompanied by erythema and pain; Grade 2: 1 ulcer larger than 1.0 cm and several small ulcers in the oral mucosa; Grade 3: 2 ulcers larger than 1.0 cm and several small ulcers in the oral mucosa; Grade 4: 2 or more ulcers larger than 1.0 cm and / or fused ulcers in the oral mucosa.

[0106] 2. Diagnostic criteria: After medication, complete disappearance of oral mucositis and erythema was considered a significant effect; improvement in oral mucositis compared to before treatment, with a reduction of ulcer area exceeding 65%, was considered effective; no improvement or even worsening of oral mucositis was considered ineffective. The incidence and grading of oral mucositis were assessed in both groups on day 3 of medication, and the treatment progress of patients with oral mucositis was observed on day 5.

[0107] 1.4 Statistical methods: The x-squared value was used. 2 The test showed that the difference was statistically significant (P < 0.05).

[0108] 3. Treatment Methods: A total of 100 eligible inpatients were selected and divided into 5 groups of 20 patients each. Each group applied the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5 of this invention to the oral ulcers three times daily (morning, noon, and evening), at a dose of 1-1.5g each time. Evaluation criteria were used to assess the severity of mucosal damage and pain levels after using the "Traditional Chinese Medicine Oral Antibacterial Ointment." The results are shown in Table 3.

[0109] Table 3: Antibacterial effect of the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Example 1 of the present invention

[0110]

[0111]

[0112] The results showed that among 100 patients with oral mucositis treated with the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5, the efficacy rate of the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1, 3, and 4 was as high as 95%. Except for one case where the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Example 5 was ineffective, all others were significantly effective or effective, indicating that the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in this invention has a significant therapeutic effect on oral mucositis.

[0113] Experiment Example 4

[0114] The effects of the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Examples 1-5 of this invention on the serum concentration of rats were investigated.

[0115] 1. Instruments and reagents:

[0116] 1.1 Instruments: Shimadzu high-performance liquid chromatograph, Avanti high-performance centrifuge

[0117] 1.2 Reagent: Chromatographic grade methanol.

[0118] 2. Medicine: "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared according to Examples 1-5.

[0119] 3. Buffer solution: 0.5 mol / L phosphate buffer, 4% isopropanol chloroform solution.

[0120] Experimental animals: Wistar rats

[0121] 4. Administration method in rats: One hundred Wistar rats were divided into 5 groups of 20 each. The rats were anesthetized by ether inhalation. After disinfecting the skin under the neck with 75% ethanol, a 1cm incision was made. Subcutaneous fat and muscle tissues were dissected with forceps, the esophagus was identified and ligated with sutures, and the skin was then sutured. Thirty minutes after the ligation, 1.5g of the traditional Chinese medicine oral antibacterial ointment prepared in Examples 1-5 was applied to the rat's oral cavity until it was full. Ten minutes later, the ointment residue was washed out. Blood samples were collected at 30, 60, 90, and 120 minutes after administration.

[0122] 5. Sample pretreatment and testing:

[0123] 5.1 Take blood samples from different times mentioned above and centrifuge them at 2500 r / min for 15 min for later use;

[0124] 5.2 Take 0.2 ml of serum into 5 ml centrifuge tubes, add 0.2 ml of 0.5 mol / L phosphate buffer and 3 ml of 5% isopropanol chloroform solution in sequence. Place the centrifuge tubes on a liquid mixer to mix and extract for 5 min, then centrifuge at 2500 r / min for 10 min. Aspirate the organic layer with a 5 ml glass syringe and filter through a 0.5 μm organic membrane. Drop the filtered liquid into a pointed-bottom test tube and dry it in a 40℃ water bath with air. Dissolve the residue in 0.5 ml of mobile phase. Quantitatively analyze the treated samples using Shimadzu high-performance liquid chromatography with external standard method, and calculate the dynamic changes of dracosan B in the serum samples. The results are shown in Table 4.

[0125] Table 4: Dynamic changes in dermal dermal B levels in rat serum

[0126]

[0127]

[0128] Results: The oral antibacterial ointment prepared according to this invention showed that within 30 minutes... - The serum concentration was highest at 90 minutes and began to decrease after 90 minutes, indicating that the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in this invention has the effect of good absorption by the oral mucosa and rapid effect.

[0129] Experimental Example 5:

[0130] The inhibitory effect of the "Traditional Chinese Medicine Oral Antibacterial Ointment" of this invention on tongue cancer cells was investigated.

[0131] 1. Experimental sample: "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Example 1 of this invention.

[0132] 2. Experimental materials: Tongue tumor cell line: human tongue cancer cell line Tca-8113, cultured in RPMI-1649 medium at 37℃, 5% CO2, and 100% relative humidity, with adherent cells passaged by 0.25% trypsin digestion.

[0133] 3. Experimental method: The inhibitory effect of "Traditional Chinese Medicine Oral Antibacterial Ointment" on tumor cell growth was determined by the MTT colorimetric method.

[0134] Cells in the logarithmic growth phase were collected and prepared into a cell suspension using fresh RPMI-1649 culture medium, with 1 x 102 cells suspended in the suspension. 5 0.8 x 10 cells / ml adherent cells 5 Cells / ml. Suspended cells were seeded into 96-well plates after adding different concentrations of the experimental drug; adherent cells were first seeded into 96-well plates at 90 μl per well, and different concentrations of the experimental drug were added after 24 h. The final volume was 100 μl per well, with 3 parallel wells per group, for a total of 4 groups: test drug group A (culture medium + cell suspension + different concentrations of test drug), negative control group B (culture medium + cell suspension), drug color control group D (culture medium + different concentrations of test drug), and blank control group C (culture medium + physiological saline). The concentrations of the test drug were 20 μg / ml, 40 μg / ml, and 60 μg / ml, respectively. After culturing at 37℃ in a 5% CO2 incubator for 72 h, 10 μl of MTT solution was added to each well, vortexed, and cultured for another 4 h. Then, 90 μl of SDS was added to terminate the culture, and the plates were shaken for 10 min at room temperature. The absorbance (OD value) at 570 nm was measured using a microplate reader. The experiment was repeated 3 times. The growth inhibition rate is calculated using the following formula: Growth inhibition rate (%) = [(Mean OD of Group B - Mean OD of Group C) - (Mean OD of Group A - Mean OD of Group D)] / [Mean OD of Group B - Mean OD of Group D] x 100%.

[0135] 4. The inhibition rate of the drug on the human tongue cancer cell line Tca-8113 is shown in Table 1.

[0136] Table 1: Inhibition rate results for Tca-8113.

[0137] Drug concentration 20 (μg / ml) 40 (μg / ml) 60 (μg / ml) Example 1 55.32 61.28 71.51

[0138] The above examples demonstrate that the composition prepared in Example 1 of this invention has a good inhibitory effect on the growth of the human tongue cancer cell line PTca8113. This proves that the "Traditional Chinese Medicine Oral Antibacterial Ointment" prepared in Example 1 of this invention has an inhibitory effect on the activity of tongue cancer cells.

[0139] In addition, regarding the study on the dosage of the "Traditional Chinese Medicine Oral Antibacterial Ointment" of the present invention, based on the experimental results of Experimental Examples 1-5, the dosage for each use is tentatively determined to be 0.5-2.0g, preferably 1.0g. The inventors will continue to conduct research in this regard to determine a better dosage.

Claims

1. A traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... It is composed of Chinese herbal extracts and excipients.

2. The oral antibacterial ointment of traditional Chinese medicine according to claim 1, its preparation method and application, characterized in that... The herbal extract is composed of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract.

3. According to claim 1, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The excipients consist of thickeners, anionic surfactants, softeners, sweeteners, preservatives, and water.

4. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... By weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract are 1-2%, 1.5-2%, 1-3%, 0.5-1.5%, and 0.5-1.5%, respectively.

5. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The percentages by weight of Dragon's Blood Extract, Artemisia annua Extract, Honeysuckle Extract, Licorice Extract, and Forsythia Extract are 1.0%, 1.5%, 1.0%, 0.5%, and 0.5%, respectively.

6. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... By weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract were 2.0%, 2.0%, 3.0%, 1.5%, and 1.5%, respectively.

7. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... By weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract were 1.5%, 1.7%, 1.7%, 1.0%, and 0.8%, respectively.

8. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... By weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract were 1.8%, 1.5%, 2.5%, 1.0%, and 1.3%, respectively.

9. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... By weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract were 1.6%, 2.0%, 1.5%, 1.2%, and 1.3%, respectively.

10. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... By weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract were 1.5%, 1.8%, 2.2%, 1.3%, and 1.4%, respectively.

11. According to claim 2, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... Preferred: by weight percentage, the proportions of dragon's blood extract, artemisia annua extract, honeysuckle extract, licorice extract, and forsythia extract are 2.0%, 1.8%, 2.0%, 1.0%, and 1.0%, respectively.

12. According to claim 3, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The thickener includes, but is not limited to, sodium carboxymethyl cellulose (CMC), hydroxyethyl cellulose, carbomer resin, xanthan gum, polyethylene glycol 400, polyethylene glycol 150, polyethylene glycol 2000, modified guar gum, carrageenan, or one or more thereof, preferably xanthan gum and polyethylene glycol 400.

13. According to claim 3, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The anionic surfactant (which also acts as a transdermal absorption enhancer) includes, but is not limited to, one or more of sulfosuccinate, sodium lauryl sulfate, and sodium lauroyl sarcosinate, preferably sodium lauryl sulfate and sodium lauroyl sarcosinate.

14. According to claim 3, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The softener includes, but is not limited to, glycerin, diethylaminoethanol, triethanolamine, and oleyl alcohol polyoxyethylene ether, with glycerin being preferred.

15. According to claim 3, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The sweeteners include, but are not limited to, sucrose, steviol, glycerin, sorbitol, and mannitol, with sorbitol being preferred.

16. According to claims 1-15, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that the preparation method is as follows: 16.1 Prescription: Prepare 1000g Phase A: Dragon's Blood Extract 2.0%, Artemisia annua Extract 1.8%, Honeysuckle Extract 2.0%, Licorice Extract 1.0%, Forsythia Extract 1.0%, Sodium Lauryl Sulfate 2.0%, Sodium Lauroyl Sarcosinate 1.5%, Xanthan Gum 30%, Glycerin 45%, Water as needed. Phase B: Sorbitol 2.0%, Polyethylene Glycol 400 10%, Eugenol 1%, Phase C: Sodium benzoate 0.5%, 16.2 Preparation method: 16.2.1 First, add an appropriate amount of water from phase A to the emulsification pot. While stirring, slowly add the extracts of dragon's blood, artemisia annua, honeysuckle, licorice, and forsythia, respectively. After complete saturation, start stirring at 30-50 rpm until completely dissolved. Then, add the other raw materials from phase A. Heat to 80°C and emulsify at 2000-2500 rpm. Stop stirring when the temperature drops to 50-60°C to obtain phase A solution. 16.2.2 Slowly add phase B raw material to phase A solution, and continue stirring for 45-60 minutes until the solution is homogeneous, thus obtaining phase B solution. 16.2.3 Add sodium benzoate from phase C to the solution in phase B, add water to 1000g, and start stirring at 30-50 r / min until the solution is homogeneous. Stop stirring to obtain the phase C solution. 16.2.4 The C-phase solution was degassed under vacuum to eliminate air bubbles, yielding an oral antibacterial paste. 16.2.5 Fill the above-mentioned oral antibacterial ointment into a clean and sterile container, seal it, protect it from light, and refrigerate it.

17. According to claim 16, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The usage and dosage of the prepared "Traditional Chinese Medicine Oral Antibacterial Ointment" are as follows: Apply the oral antibacterial ointment of the present invention to the affected area, and you can drink water or eat food after 5-10 minutes. The dosage for each use is 0.5–2.0g, preferably 1.0g.

18. According to claims 1-18, a traditional Chinese medicine oral antibacterial ointment, its preparation method, and its application, characterized in that... The Chinese herbal oral antibacterial ointment has the effects of preventing and treating oral ulcers, treating swollen and painful gums, repairing teeth, removing dental plaque and tartar, protecting gums and oral mucosa, and inhibiting and treating tongue cancer cells.

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