Pharmaceutical composition containing effective components of clove and preparation method of pharmaceutical composition

Abstract

The invention relates to a pharmaceutical composition containing effective components of clove and a preparation method of the pharmaceutical composition, and belongs to the technical field of pharmaceutical compositions. In order to solve the problems that an existing medicine for treating oral ulcer is large in irritation and prone to forming medicine dependence and medicine resistance, the invention provides a medicine composition containing an effective component of clove. An effective component eugenol of clove, an effective component berberine of coptis chinensis, an effective component rehmannia polysaccharide of radix rehmanniae recen and an effective component d-borneol of borneol are taken as effective medicine components, and the treatment effect on the oral ulcer is enhanced through a synergistic effect. According to the invention, the pharmaceutical composition is further prepared into a viscous gel preparation which can be attached to a mucous membrane affected part with oral ulcer for a long time to continuously absorb effective pharmaceutical ingredients in the gel, so that the problems that the existing spray, powder and the like are easily diluted by saliva and are short in retention time are solved. The viscous gel prepared by the invention can form a water-retaining film at an ulcer affected part, so that the stimulation to the affected part is reduced, and the pain of a patient is relieved.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical compositions, and in particular relates to a pharmaceutical composition containing clove effective ingredients and a preparation method thereof. Background Art

[0002] Oral ulcer, also known as aphthous ulcer, is a common disease in stomatology. It refers to ulcerative lesions in the oral mucosa, which are mostly seen in the inner side of the lips, tongue, tongue ventral surface, buccal mucosa, vestibule groove, soft palate, etc. The mucosa in these parts lacks keratinization or has poor keratinization, so ulcerative lesions are prone to occur, accompanied by local burning pain.

[0003] Chinese and Western medicine use different methods and drugs to treat oral ulcers, but both aim to relieve pain, promote healing and prevent recurrence. Chinese medicine believes that the cause of oral ulcers is related to the imbalance of yin and yang in the body and the exuberance of internal heat. It often uses heat-clearing and detoxifying drugs and yin-nourishing and body fluid-promoting drugs, which can nourish yin and clear heat, detoxify and reduce swelling through oral administration. There are also external medicines such as Bingpengsan and Xileisan. Western medicine believes that it is related to viral infection, trace element and vitamin deficiency, autoimmune disorder and local trauma. It mainly uses local treatment methods, including the use of oral sprays, oral films, ointments, etc., including local antibacterial drugs, local corticosteroids, local analgesics, etc., to relieve pain and promote healing.

[0004] Although existing drugs for treating oral ulcers can relieve patients' pain and discomfort to a certain extent, they still have some defects. Some oral ulcer drugs, such as Bingpengsan, are highly irritating to the oral cavity. Long-term use can damage the oral mucosa and may also cause drug dependence. Once the drug is stopped, oral ulcers may recur. Continuous use of ulcer patches containing hormone ingredients will also be detrimental to ulcer healing and may even lead to drug resistance. Due to the complex oral environment, some drugs are easily washed away by saliva, requiring patients to use the drugs repeatedly, which increases the inconvenience of use. Summary of the invention

[0005] In order to solve the problems that existing drugs for treating oral ulcers are highly irritating, easily form drug dependence and drug resistance, and are inconvenient to use topically, the present invention provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0006] The technical solution of the present invention:

[0007] A pharmaceutical composition containing clove effective ingredients, comprising the following effective ingredients in parts by weight: 20-30 parts of eugenol as the effective ingredient of clove, 10-20 parts of berberine as the effective ingredient of coptis root, 5-10 parts of rehmannia polysaccharide as the effective ingredient of raw rehmannia root, and 5-15 parts of dextrorotatory borneol as the effective ingredient of borneol.

[0008] Furthermore, it contains the following active ingredients in parts by weight: 30 parts of eugenol, an active ingredient of cloves, 15 parts of berberine, an active ingredient of coptis chinensis, 8 parts of rehmannia polysaccharide, an active ingredient of raw rehmannia, and 12 parts of borneol, an active ingredient of borneol.

[0009] Furthermore, the pharmaceutical composition is a viscous gel preparation, and also contains the following components in parts by mass: 1 to 3 parts of Tween-80, 5 to 10 parts of glycerol, 2 to 3 parts of an amidating agent, 5 to 6 parts of dopamine hydrochloride, 100 to 120 parts of a sodium hyaluronate aqueous solution with a mass concentration of 2 to 3%, and 100 parts of deionized water.

[0010] Furthermore, the amidation reagent is NHS (N-hydroxysuccinimide) and EDC·HCl (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) in a mass ratio of 2:3.

[0011] A method for preparing a pharmaceutical composition containing clove active ingredients, wherein the pharmaceutical composition is a viscous gel preparation, and the preparation method comprises the following steps:

[0012] Step 1: Preparation of drug-loaded microemulsion:

[0013] Dissolve 10-20 parts of berberine, an effective ingredient of Coptis chinensis, 5-10 parts of Rehmannia glutinosa polysaccharide, 1-3 parts of Tween-80 and 5-10 parts of glycerol in 100 parts of deionized water, and fully stir at a first speed to obtain an aqueous phase; use 20-30 parts of eugenol, an effective ingredient of clove, as an oil phase, add the oil phase to the aqueous phase under stirring at a first speed, stir at a second speed for a certain period of time, and then perform ultrasonic treatment to obtain a drug-loaded microemulsion;

[0014] Step 2: Preparation of viscous gel preparation:

[0015] The drug-loaded microemulsion prepared in step 1 and 5 to 15 parts of borneol active ingredient dextrorotatory borneol powder are added to 100 to 120 parts of a sodium hyaluronate aqueous solution with a mass concentration of 2 to 3%, and after fully stirring at a third speed, 2 to 3 parts of an amidation reagent are added to the obtained mixed system, and stirring is continued at the third speed for a certain time, and then 5 to 6 parts of dopamine hydrochloride are added under an inert atmosphere, and after stirring at the third speed for a certain time, homogenization is performed to obtain a viscous excipient preparation.

[0016] Furthermore, in step 1, the first rotation speed is 200-300 rpm, the stirring time for fully stirring the water phase is 30-45 min, and the oil phase is added to the water phase by slowly dropping the oil phase into the water phase at 0.5-1.0 mL / min.

[0017] Furthermore, in step 1, the second rotation speed is 600-800 rpm, the stirring time at the second rotation speed is 10 min, the power of the ultrasonic treatment is 100-150 W, and the ultrasonic treatment time is 20-30 min.

[0018] Furthermore, the borneol active ingredient D-borneol powder in step 2 is obtained by grinding D-borneol and then passing it through a 20-mesh or 30-mesh sieve.

[0019] Furthermore, the third rotation speed in step 2 is 800-1000 rpm, the time for sufficient stirring at the third rotation speed is 1-3 h, the stirring time after adding the amidation reagent is 1-2 h, and the stirring time after adding dopamine hydrochloride is 12-18 h.

[0020] Furthermore, the homogenization speed in step 2 is 2000-2200 rpm, and the homogenization time is 30-60 min.

[0021] Beneficial effects of the present invention:

[0022] The invention provides a pharmaceutical composition with eugenol, an effective component of clove, berberine, an effective component of coptis root, rehmannia polysaccharide, an effective component of raw rehmannia root, and borneol, an effective component of borneol, as effective components, and the pharmaceutical composition is used for treating oral ulcers. Eugenol, an effective component of clove, has a strong antibacterial effect, can inhibit the growth of various bacteria, and also has an anti-inflammatory effect, and can reduce the inflammatory response of oral mucosa; berberine, an effective component of coptis root, has a strong inhibitory effect on bacteria, fungi and viruses, and can also promote the repair of oral mucosa. Rehmannia polysaccharide, an effective component of raw rehmannia root, has immunomodulatory and anti-inflammatory effects, can enhance the immune function of the matrix, and promote the healing of oral mucosa. At the same time, rehmannia polysaccharide can also reduce the inflammatory response of oral mucosa and relieve pain and discomfort. Borneol, an effective component of borneol, has the effects of clearing away heat and detoxifying, reducing swelling and relieving pain. It can inhibit bacterial growth and reduce the inflammatory response of oral mucosa. At the same time, borneol also has the effect of promoting the repair of oral mucosa and can accelerate the healing of ulcer surface. The present invention compounds the four effective components of traditional Chinese medicines to enhance the therapeutic effect on oral ulcers through synergistic effects.

[0023] The pharmaceutical composition of the present invention does not contain hormones and will not form drug dependence. Multiple active ingredients derived from natural medicines exert therapeutic effects through multiple pathways, thereby reducing dependence on a single target and lowering the risk of overall drug resistance.

[0024] The present invention further prepares the pharmaceutical composition into a viscous gel preparation, and forms a viscous gel dressing by self-polymerization of dopamine and cross-linking with sodium hyaluronate, which can be attached to the mucosal affected area of ​​oral ulcer for a long time, continuously absorb the effective drug components in the gel, and solve the problem that the existing sprays and powders are easily diluted by saliva and have a short residence time. The viscous gel prepared by the present invention is degradable, safe and non-toxic, and can form a water-retaining film on the ulcer affected area, reduce the irritation to the affected area, and relieve the pain of the patient. DETAILED DESCRIPTION

[0025] The technical solution of the present invention is further described below in conjunction with the embodiments, but it is not limited thereto. Any modification or equivalent replacement of the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention shall be included in the protection scope of the present invention. The process equipment or devices not specifically noted in the following embodiments are all conventional equipment or devices in the art. If not specifically specified, the raw materials used in the embodiments of the present invention can be obtained commercially; if not specifically specified, the technical means used in the embodiments of the present invention are all conventional means well known to those skilled in the art.

[0026] Example 1

[0027] This embodiment provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0028] The dosage form of the pharmaceutical composition containing clove as an effective ingredient in this embodiment is a viscous gel preparation, containing the following components in parts by mass: 30 parts of eugenol as an effective ingredient of clove, 15 parts of berberine as an effective ingredient of Coptis chinensis, 8 parts of Rehmannia glutinosa polysaccharide as an effective ingredient of Rehmannia glutinosa, 12 parts of borneol as an effective ingredient, 2 parts of Tween-80, 8 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of a sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water, wherein the d-borneol is ground and passed through a 30-mesh sieve to obtain d-borneol powder.

[0029] The preparation method of the pharmaceutical composition containing clove effective ingredient in this embodiment comprises the following steps:

[0030] Step 1: Preparation of drug-loaded microemulsion:

[0031] Berberine, Rehmannia glutinosa polysaccharide, Tween-80 and glycerol were dissolved in deionized water at 65°C, and stirred at 300 rpm for 30 min to obtain an aqueous phase; eugenol was used as the oil phase, and the oil phase was slowly added to the aqueous phase at 0.5 mL / min under continuous stirring at 300 rpm, stirred at 800 rpm for 10 min, and then ultrasonically treated with 120 W power for 20 min to obtain a microemulsion;

[0032] Step 2: Preparation of viscous gel:

[0033] The microemulsion prepared in step 1 and borneol powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 800 rpm for 3 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 800 rpm for 30 min. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 12 h. The mixture was homogenized at a speed of 2000 rpm for 60 min to obtain a viscous gel preparation.

[0034] Example 2

[0035] This embodiment provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0036] The dosage form of the pharmaceutical composition containing clove as an effective ingredient in this embodiment is a viscous gel preparation, containing the following components in parts by mass: 20 parts of eugenol as an effective ingredient of clove, 10 parts of berberine as an effective ingredient of Coptis chinensis, 5 parts of Rehmannia glutinosa polysaccharide as an effective ingredient of Rehmannia glutinosa, 15 parts of borneol as an effective ingredient, 1 part of Tween-80, 5 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of a sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water, wherein the d-borneol is ground and passed through a 30-mesh sieve to obtain d-borneol powder.

[0037] The preparation method of the pharmaceutical composition containing clove effective ingredient in this embodiment comprises the following steps:

[0038] Step 1: Preparation of drug-loaded microemulsion:

[0039] Berberine, Rehmannia glutinosa polysaccharide, Tween-80 and glycerol were dissolved in deionized water at 65°C, and stirred at 200 rpm for 45 min to obtain an aqueous phase; eugenol was used as an oil phase, and the oil phase was slowly added to the aqueous phase at 0.6 mL / min under continuous stirring at 200 rpm, stirred at 600 rpm for 10 min, and then ultrasonically treated at 100 W power for 30 min to obtain a microemulsion;

[0040] Step 2: Preparation of viscous gel:

[0041] The microemulsion prepared in step 1 and borneol powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 900 rpm for 2 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 900 rpm for 60 min. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 900 rpm for 15 h. The mixture was homogenized at a speed of 2000 rpm for 60 min to obtain a viscous gel preparation.

[0042] Example 3

[0043] This embodiment provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0044] The dosage form of the pharmaceutical composition containing clove as an effective ingredient in this embodiment is a viscous gel preparation, containing the following components in parts by mass: 15 parts of eugenol as an effective ingredient of clove, 20 parts of berberine as an effective ingredient of Coptis chinensis, 7 parts of Rehmannia glutinosa polysaccharide as an effective ingredient of Rehmannia glutinosa, 10 parts of borneol as an effective ingredient, 3 parts of Tween-80, 10 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of a sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water, wherein the d-borneol is ground and passed through a 30-mesh sieve to obtain d-borneol powder.

[0045] The preparation method of the pharmaceutical composition containing clove effective ingredient in this embodiment comprises the following steps:

[0046] Step 1: Preparation of drug-loaded microemulsion:

[0047] Berberine, Rehmannia glutinosa polysaccharide, Tween-80 and glycerol were dissolved in deionized water at 65°C, and stirred at 300 rpm for 30 min to obtain an aqueous phase; eugenol was used as an oil phase, and the oil phase was slowly added to the aqueous phase at 0.8 mL / min under continuous stirring at 300 rpm, stirred at 700 rpm for 10 min, and then ultrasonically treated with 150 W power for 20 min to obtain a microemulsion;

[0048] Step 2: Preparation of viscous gel:

[0049] The microemulsion prepared in step 1 and borneol powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 1000 rpm for 1 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 1000 rpm for 30 min. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 1000 rpm for 18 h. The mixture was homogenized at a speed of 2000 rpm for 60 min to obtain a viscous gel preparation.

[0050] Example 4

[0051] This embodiment provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0052] The dosage form of the pharmaceutical composition containing clove as an effective ingredient in this embodiment is a viscous gel preparation, containing the following components in parts by mass: 30 parts of eugenol as an effective ingredient of clove, 20 parts of berberine as an effective ingredient of Coptis chinensis, 10 parts of Rehmannia glutinosa polysaccharide as an effective ingredient of Rehmannia glutinosa, 5 parts of borneol as an effective ingredient, 2 parts of Tween-80, 7 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of a sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water, wherein the d-borneol is ground and passed through a 30-mesh sieve to obtain d-borneol powder.

[0053] The preparation method of the pharmaceutical composition containing clove effective ingredient in this embodiment comprises the following steps:

[0054] Step 1: Preparation of drug-loaded microemulsion:

[0055] Berberine, Rehmannia glutinosa polysaccharide, Tween-80 and glycerol were dissolved in deionized water at 65°C, and stirred at 200 rpm for 45 min to obtain an aqueous phase; eugenol was used as the oil phase, and the oil phase was slowly added to the aqueous phase at 1.0 mL / min under continuous stirring at 200 rpm, stirred at 800 rpm for 10 min, and then ultrasonically treated with 120 W power for 20 min to obtain a microemulsion;

[0056] Step 2: Preparation of viscous gel:

[0057] The microemulsion prepared in step 1 and borneol powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 800 rpm for 3 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 800 rpm for 60 min. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 12 h. The mixture was homogenized at a speed of 2000 rpm for 60 min to obtain a viscous gel preparation.

[0058] Example 5

[0059] This embodiment provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0060] The dosage form of the pharmaceutical composition containing clove as an effective ingredient in this embodiment is a viscous gel preparation, containing the following components in parts by mass: 20 parts of eugenol as an effective ingredient of clove, 10 parts of berberine as an effective ingredient of Coptis chinensis, 6 parts of Rehmannia glutinosa polysaccharide as an effective ingredient of Rehmannia glutinosa, 8 parts of dextrorotatory borneol as an effective ingredient of borneol, 1 part of Tween-80, 6 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of a sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water, wherein the dextrorotatory borneol is ground and passed through a 30-mesh sieve to obtain dextrorotatory borneol powder.

[0061] The preparation method of the pharmaceutical composition containing clove effective ingredient in this embodiment comprises the following steps:

[0062] Step 1: Preparation of drug-loaded microemulsion:

[0063] Berberine, Rehmannia glutinosa polysaccharide, Tween-80 and glycerol were dissolved in deionized water at 65°C, and stirred at 300 rpm for 30 min to obtain an aqueous phase; eugenol was used as the oil phase, and the oil phase was slowly added to the aqueous phase at 0.6 mL / min under continuous stirring at 300 rpm, stirred at 600 rpm for 10 min, and then ultrasonically treated with 150 W power for 20 min to obtain a microemulsion;

[0064] Step 2: Preparation of viscous gel:

[0065] The microemulsion prepared in step 1 and borneol powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 900 rpm for 2 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 900 rpm for 30 min. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 900 rpm for 15 h. The mixture was homogenized at a speed of 2000 rpm for 60 min to obtain a viscous gel preparation.

[0066] Example 6

[0067] This embodiment provides a pharmaceutical composition containing clove effective ingredients and a preparation method thereof.

[0068] The dosage form of the pharmaceutical composition containing clove as an effective ingredient in this embodiment is a viscous gel preparation, containing the following components in parts by mass: 15 parts of eugenol as an effective ingredient of clove, 15 parts of berberine as an effective ingredient of Coptis chinensis, 9 parts of Rehmannia glutinosa polysaccharide as an effective ingredient of Rehmannia glutinosa, 10 parts of borneol as an effective ingredient, 3 parts of Tween-80, 5 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of a sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water, wherein the d-borneol is ground and passed through a 30-mesh sieve to obtain d-borneol powder.

[0069] The preparation method of the pharmaceutical composition containing clove effective ingredient in this embodiment comprises the following steps:

[0070] Step 1: Preparation of drug-loaded microemulsion:

[0071] Berberine, Rehmannia glutinosa polysaccharide, Tween-80 and glycerol were dissolved in deionized water at 65°C, and stirred at 200 rpm for 45 min to obtain an aqueous phase; eugenol was used as an oil phase, and the oil phase was slowly added to the aqueous phase at 0.5 mL / min under continuous stirring at 200 rpm, stirred at 700 rpm for 10 min, and then ultrasonically treated at 100 W power for 30 min to obtain a microemulsion;

[0072] Step 2: Preparation of viscous gel:

[0073] The microemulsion prepared in step 1 and borneol powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 1000 rpm for 1 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 1000 rpm for 60 min. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 1000 rpm for 18 h. The mixture was homogenized at 2000 rpm for 60 min to obtain a viscous gel preparation.

[0074] Comparative Example 1

[0075] This comparative example provides a blank gel without any drug component.

[0076] The blank gel of this comparative example contains the following components in parts by mass: 1 part of amidation reagent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water.

[0077] The preparation method of the blank gel of this comparative example comprises the following steps:

[0078] Deionized water was added to the sodium hyaluronate aqueous solution, and NHS and EDC·HCl were added after stirring at 800 rpm. The mixture was stirred for 30 min at 800 rpm, and then dopamine hydrochloride was added to the obtained mixture under nitrogen atmosphere. The mixture was stirred at 800 rpm for 12 h and homogenized at 2000 rpm for 60 min to obtain a blank gel.

[0079] Test Example 1

[0080] This test example verifies the effects of the microemulsion prepared in step 1 of Example 1, the viscous gel prepared in Example 2, and a blank viscous gel in treating oral ulcers through animal experiments.

[0081] 1. Experimental Animals:

[0082] Forty healthy SD rats weighing 200±10g were selected, half of which were male and half were female.

[0083] 2. Construction of oral ulcer model rats:

[0084] Oral ulcer model was established in SD rats. The rats were anesthetized and small cotton balls were soaked with 90% phenol solution. The lower end of the glass tube with the built-in small cotton ball was placed flat on the buccal mucosa about 4 mm inside the left corner of the mouth of the rat. The phenol solution flowed out from the through hole at the lower end of the glass tube. The cautery was performed for 30 seconds to ensure sufficient burning effect on the mucosa, forming a white lesion with a diameter of about 3 mm. The size of the ulcer was expressed as the ulcer diameter (mm), and the diameter was measured with a divider and SF2000 electronic digital caliper.

[0085] 3. Grouping

[0086] The rats with oral ulcer model were randomly divided into 4 groups, 10 rats in each group, and the medication conditions of each group were as follows:

[0087] Drug-loaded gel group: Apply the viscous gel prepared in Example 1 to the affected area of ​​oral ulcers, and apply the amount of the drug to cover the affected area of ​​the ulcer, once a day;

[0088] Drug-loaded microemulsion group: Apply the microemulsion prepared in step 1 of Example 1 to the affected area of ​​oral ulcers in an amount sufficient to cover the affected area of ​​ulcers. Apply the drug once in the morning and once in the evening every day.

[0089] Blank gel group: The blank gel prepared in Comparative Example 1 was applied to the affected area of ​​oral ulcers in an amount sufficient to cover the affected area of ​​the ulcers, and the drug was administered once a day;

[0090] Blank control group: a blank control group without any treatment;

[0091] 4. Experimental Results

[0092] The healing status of oral ulcers in each group of animals was observed and recorded daily. The results showed that the average time for ulcer healing in rats in the drug-loaded gel group was 6 days, the average time for ulcer healing in rats in the drug-loaded microemulsion group was 10 days, the average time for ulcer healing in rats in the blank gel group was 14 days, and the ulcer healing time in rats in the blank control group without any treatment was 20 days.

[0093] The experimental results show that the wound healing speed of the viscous gel prepared by the present invention, which is applied only once a day, is better than the wound healing speed of the microemulsion group, which is applied twice a day. This shows that the viscous gel preparation prepared by the present invention can stay on the surface of the ulcer wound for a long time and will not be diluted by saliva. Eugenol, berberine, Rehmannia polysaccharide and borneol can be fully absorbed by the ulcer wound and exert synergistic drug effects, reduce the inflammatory response of the oral ulcer mucosa, and promote the healing of the oral mucosa. At the same time, the effective ingredients of traditional Chinese medicine prevent and treat the recurrence of oral ulcers through multi-target treatment of clearing away heat and detoxification, reducing swelling and relieving pain, reducing the risk of drug resistance. The healing speed of the blank gel group is better than that of the blank treatment group because the blank gel can form a water-retaining film at the ulcer affected part, reducing further stimulation of saliva, food, etc. to the affected part, so the viscous gel layer also plays a role in accelerating wound healing.

Claims

1. A pharmaceutical composition containing clove effective ingredients, characterized in that: The active ingredients contained are as follows: 20-30 parts of eugenol, an active ingredient of cloves; 10-20 parts of berberine, an active ingredient of coptis root; 5-10 parts of rehmannia polysaccharide, an active ingredient of raw rehmannia root; and 5-15 parts of borneol, an active ingredient of borneol.

2. A pharmaceutical composition containing clove active ingredients according to claim 1, characterized in that: It contains the following active ingredients in parts by weight: 30 parts of eugenol, an active ingredient of cloves; 15 parts of berberine, an active ingredient of coptis chinensis; 8 parts of rehmannia polysaccharide, an active ingredient of raw rehmannia root; and 12 parts of dextrorotatory borneol, an active ingredient of borneol.

3. A pharmaceutical composition containing clove active ingredients according to claim 1 or 2, characterized in that: The pharmaceutical composition is a viscous gel preparation, and further contains the following components in parts by weight: 1-3 parts of Tween-80, 5-10 parts of glycerol, 2-3 parts of amidation reagent, 5-6 parts of dopamine hydrochloride, 100-120 parts of sodium hyaluronate aqueous solution with a mass concentration of 2-3% and 100 parts of deionized water.

4. A pharmaceutical composition containing clove effective ingredients according to claim 3, characterized in that: The amidation reagent is NHS and EDC·HCl in a mass ratio of 2:

3.

5. A method for preparing a pharmaceutical composition containing clove effective ingredients, characterized in that: The pharmaceutical composition is a viscous gel preparation, and the preparation method comprises the following steps: Step 1: Preparation of drug-loaded microemulsion: Dissolve 10-20 parts of berberine, an effective ingredient of Coptis chinensis, 5-10 parts of Rehmannia glutinosa polysaccharide, 1-3 parts of Tween-80 and 5-10 parts of glycerol in 100 parts of deionized water, and fully stir at a first speed to obtain an aqueous phase; use 20-30 parts of eugenol, an effective ingredient of clove, as an oil phase, add the oil phase to the aqueous phase under stirring at a first speed, stir at a second speed for a certain period of time, and then perform ultrasonic treatment to obtain a drug-loaded microemulsion; Step 2: Preparation of viscous gel preparation: The drug-loaded microemulsion prepared in step 1 and 5 to 15 parts of borneol active ingredient dextrorotatory borneol powder are added to 100 to 120 parts of a sodium hyaluronate aqueous solution with a mass concentration of 2 to 3%, and after fully stirring at a third speed, 2 to 3 parts of an amidation reagent are added to the obtained mixed system, and stirring is continued at the third speed for a certain time, and then 5 to 6 parts of dopamine hydrochloride are added under an inert atmosphere, and after stirring at the third speed for a certain time, homogenization is performed to obtain a viscous excipient preparation.

6. A method for preparing a pharmaceutical composition containing clove effective ingredients according to claim 5, characterized in that: Step 1: The first rotation speed is 200-300 rpm, the stirring time for fully stirring the water phase is 30-45 min, and the oil phase is added to the water phase by slowly dropping the oil phase into the water phase at 0.5-1.0 mL / min.

7. A method for preparing a pharmaceutical composition containing clove active ingredients according to claim 5 or 6, characterized in that: In step 1, the second rotation speed is 600-800 rpm, the stirring time at the second rotation speed is 10 min, the power of the ultrasonic treatment is 100-150 W, and the ultrasonic treatment time is 20-30 min.

8. A method for preparing a pharmaceutical composition containing clove effective ingredients according to claim 7, characterized in that: The borneol active ingredient dextrorotatory borneol powder in step 2 is obtained by grinding dextrorotatory borneol and then passing it through a 20-mesh or 30-mesh sieve.

9. A method for preparing a pharmaceutical composition containing clove effective ingredients according to claim 8, characterized in that: In step 2, the third rotation speed is 800-1000 rpm, the time for sufficient stirring at the third rotation speed is 1-3 hours, the stirring time after adding the amidation reagent is 1-2 hours, and the stirring time after adding dopamine hydrochloride is 12-18 hours.

10. A method for preparing a pharmaceutical composition containing clove active ingredients according to claim 9, characterized in that: The homogenization speed in step 2 is 2000-2200 rpm, and the homogenization time is 30-60 min.