Compound oral ulcer repairing composition of Jinberry Fuzhuan tea extract and probiotics and preparation method of compound oral ulcer repairing composition

Abstract

The invention provides a Jinberry Fuzhuan tea extract and probiotic compounded oral ulcer repairing composition and a preparation method thereof, and the Jinberry Fuzhuan tea extract and probiotic compounded oral ulcer repairing composition comprises the following components in percentage by mass: 5%-20% of a Jinberry Fuzhuan tea extract, 5%-30% of probiotic fermentation liquor, 0.1%-1% of sodium hyaluronate, 0.05%-0.2% of zinc ions, 20%-40% of an abrasive, 10%-30% of a wetting agent, 1%-2% of a surfactant and the balance of water. And the balance of pharmaceutically acceptable auxiliary materials containing spices, sweeteners, pH regulators and water. According to the composition, the ulcer recurrence rate is reduced through anti-inflammatory, antibacterial and mucous membrane repair multiple mechanisms, and experiments show that the antibacterial effect of the composition on S. mutans is improved by 30%, the healing time of an animal model is shortened by 40%, and the recurrence rate is reduced to 15% after clinical 6 months. Targeted drug delivery is realized by adopting a spray / gel dosage form, an ulcer surface is accurately covered to improve the efficacy utilization rate, and the oral care composition has a wide application prospect and can be expanded to the field of daily oral care.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of oral care and medicine, in particular to a kind of goldberry brick tea extract and probiotic compound oral ulcer repair composition and preparation method thereof, for the repair and prevention of oral ulcer, with anti-inflammatory, antibacterial and multiple effects of mucosa repair. BACKGROUND

[0002] In the field of oral ulcer treatment, there are related patent technologies disclosed. For example, the existing patent (CN1130198C) discloses an oral ulcer treatment agent containing total sugar components of Actinidia polygama. The treatment agent utilizes the anti-inflammatory effect of total sugar components of Actinidia polygama to achieve certain effect in clinical trials, with a total effective rate of 96.67%. However, this technology still has the following significant limitations:

[0003] 1. Single mechanism of action: only relying on the anti-inflammatory effect of Actinidia polygama extract, it cannot fundamentally regulate the oral microecological environment and is difficult to solve the problem of ulcer recurrence. The occurrence of oral ulcer is related to many factors, among which the imbalance of oral microecology is one of the important reasons. The overgrowth of pathogenic bacteria can destroy the oral mucosal barrier, leading to repeated ulceration. However, this patent technology does not involve the regulation of oral microecology, and cannot effectively reduce the recurrence rate of ulcer.

[0004] 2. Defects in dosage form: tablet form is not conducive to targeted action in the ulcer area. Tablets need a certain time to dissolve and disperse in the oral cavity, and it is difficult to accurately cover the ulcer surface, resulting in low drug release efficiency and inability to quickly and effectively relieve ulcer symptoms and promote healing.

[0005] 3. Lack of long-term effect: no recurrence rate data is mentioned. In clinical application, patients are prone to repeated episodes. Since there is no evaluation and improvement of long-term efficacy, this treatment agent cannot meet the needs of patients for complete cure of oral ulcer. SUMMARY

[0006] The present application provides a kind of goldberry brick tea extract and probiotic compound oral ulcer repair composition and preparation method thereof to solve the above-mentioned defects existing in the prior art.

[0007] A kind of goldberry brick tea extract and probiotic compound oral ulcer repair composition, including the following components by mass percentage:

[0008] Goldberry brick tea extract: 5%-20%;

[0009] Probiotic fermentation broth: 5%-30%;

[0010] Sodium hyaluronate: 0.1%-1%;

[0011] Zinc ion: 0.05%-0.2%;

[0012] Friction agent: 20%-40%;

[0013] Humectant: 10%-30%;

[0014] Surfactant: 1%-2%;

[0015] The balance is pharmaceutically acceptable adjuvants, including spices and sweeteners, pH adjusters and water.

[0016] Further, the content of dihydromyricetin in the goldberry brick tea extract is ≥25%.

[0017] Further, the probiotic fermentation broth contains Lactobacillus reuteri DSM 17938, and the viable bacterial count is ≥1×10 8 CFU / g.

[0018] Further, the mass ratio of the goldberry brick tea extract to the probiotic fermentation broth is 1:1-1:3.

[0019] Further, the friction agent includes one or a mixture of several of silicon dioxide, calcium carbonate, calcium hydrogen phosphate.

[0020] Further, the humectant includes one or a mixture of several of glycerol, sorbitol, polyethylene glycol.

[0021] Further, the surfactant includes one or a mixture of several of sodium dodecyl sulfate, cocamide propyl betaine, sodium lauryl sulfate.

[0022] Further, the spices include one or a mixture of several of menthol, lemon essence, strawberry essence.

[0023] Further, the sweetener includes one or a mixture of several of sucrose, xylitol, sucralose.

[0024] A preparation method of a goldberry brick tea extract and probiotic compound oral ulcer repair composition, comprising the following steps:

[0025] Step one, goldberry brick tea extract preparation: including enzymolysis, ultrasonic extraction, purification steps, as follows:

[0026] Enzymolysis: add the goldberry brick tea to the cellulase and pectinase mixed solution according to the material-liquid ratio of 1:20, and enzymolysis at 50℃ for 2 hours;

[0027] Ultrasonic extraction: the mixture after enzymolysis is treated with 40kHz ultrasonic for 45 minutes, and then filtered to obtain the crude extract;

[0028] Purification: the crude extract is adsorbed by macroporous resin, eluted with 50% ethanol, concentrated and dried to obtain the extract, ensuring that the content of dihydromyricetin in the extract is greater than or equal to 20%;

[0029] Step two, preparation of L. reuteri DSM 17938 fermentation broth:

[0030] L. reuteri DSM 17938 is inoculated into MRS medium and fermented at 37 DEG C under anaerobic conditions for 48 hours;

[0031] After the fermentation is completed, the fermentation broth is centrifuged at 8000 rpm for 15 minutes, and the supernatant is taken and filtered to remove bacteria to obtain the probiotic fermentation broth;

[0032] Step three, compounding process:

[0033] In a suitable container, first mix water and humectant uniformly;

[0034] Add the rubbing agent and slowly stir until uniformly dispersed;

[0035] Add the goldberry brick tea extract, probiotic fermentation broth, sodium hyaluronate and zinc ions in sequence, and continue to stir until completely dissolved;

[0036] Add the surfactant, flavoring agent and sweetening agent, adjust the pH to 6.5-7.0, and finally add water to adjust to the required total amount, and stir uniformly before filling, wherein each component comprises the following components by mass percentage:

[0037] Goldberry brick tea extract: 5%-20%;

[0038] Probiotic fermentation broth: 5%-30%;

[0039] Sodium hyaluronate: 0.1%-1%;

[0040] Zinc ions: 0.05%-0.2%;

[0041] Rubbing agent: 20%-40%;

[0042] Humectant: 10%-30%;

[0043] Surfactant: 1%-2%;

[0044] The balance is pharmaceutically acceptable adjuvants, and the adjuvants include flavoring agents and sweetening agents, pH adjusting agents and water.

[0045] The present application has the following innovations and characteristics:

[0046] 1. Compound probiotic fermentation broth: Introduce Lactobacillus reuteri DSM 17938 fermentation broth, which can colonize in the oral cavity and regulate the balance of oral microecology, inhibit the growth and reproduction of pathogenic bacteria (such as Fusobacterium nucleatum), thereby reducing the recurrence rate of ulcers. Studies have shown that L. reuteri DSM 17938 can produce various antibacterial substances such as bacteriocins and organic acids, which can effectively inhibit the activity of pathogenic bacteria and maintain a healthy microenvironment in the oral cavity.

[0047] 2. Dual action mechanism: The extract of goldberry brick tea (containing dihydroquercetin) has the effect of quickly relieving inflammation and pain, and can quickly relieve the pain and inflammatory reaction caused by oral ulcers; the probiotic metabolites (such as bacteriocins) have the function of promoting mucosal repair, which can accelerate the healing of the ulcer surface. The two work together to treat oral ulcers from the aspects of anti-inflammatory and repair, and improve the treatment effect.

[0048] 3. Optimize the dosage form: The composition is designed as an oral spray or a gel dosage form, which can achieve precise coverage of the ulcer surface and improve the utilization rate of drug efficacy. Oral spray can quickly spray the drug on the ulcer surface to form a protective film and isolate external stimuli; the gel dosage form has good adhesion and can stay on the ulcer surface for a long time to continuously release the drug and play a therapeutic role. DETAILED DESCRIPTION

[0049] In order to make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme of the embodiments of the present application will be described clearly and completely below in combination with specific embodiments. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0050] Embodiment 1:

[0051] A compound oral ulcer repair composition of goldberry brick tea extract and probiotics, comprising the following components by mass percentage:

[0052] Goldberry brick tea extract: 10%

[0053] Probiotic fermentation broth (Lactobacillus reuteri DSM 17938): 10%

[0054] Sodium hyaluronate: 0.5%

[0055] Zinc ions: 0.1%

[0056] Friction agent (e.g. silicon dioxide): 30%

[0057] Humectant (e.g. glycerin): 20%

[0058] Surfactant (e.g. sodium lauryl sulfate): 1.5%

[0059] Flavor and sweetener (e.g. menthol, sucrose): q.s.

[0060] pH adjuster (e.g. sodium hydroxide or citric acid): q.s.

[0061] Water: q.s.

[0062] The mass ratio of the goldberry brick tea extract and the L. reuteri DSM 17938 fermentation liquor is 1:1.

[0063] Preparation:

[0064] Preparation of the goldberry brick tea extract: cellulase and pectinase mixed solution was added at a solid-liquid ratio of 1:20 (g / mL), and enzymolysis was carried out at 50°C for 2 hours, followed by ultrasonic extraction at 40 kHz for 45 minutes, macroporous resin adsorption purification, 50% ethanol elution, and concentration and drying.

[0065] Preparation of the L. reuteri DSM 17938 fermentation liquor: inoculation into MRS medium, anaerobic fermentation at 37°C for 48 hours, centrifugation at 8000 rpm for 15 minutes to take the supernatant, and filtration to remove bacteria.

[0066] Compounding: mixing the extract and the fermentation liquor, adding sodium hyaluronate, zinc ions, a friction agent, a humectant, a surfactant, a flavor and a sweetener, adjusting the pH to 6.8, adding water to a total amount of 100%, and stirring uniformly to fill into a spray

[0067] Example 2:

[0068] A kind of goldberry brick tea extract and probiotic compound oral ulcer repair composition, by mass percentage includes the following components:

[0069] Goldberry brick tea extract: 7.5%

[0070] Probiotic fermentation liquor (Lactobacillus reuteri DSM 17938): 22.5%

[0071] Sodium hyaluronate: 0.3%

[0072] Zinc ions: 0.05%

[0073] Friction agent (e.g. calcium carbonate): 25%

[0074] Humectant (e.g. sorbitol): 25%

[0075] Surfactant (e.g. cocamidopropyl betaine): 1%

[0076] Flavor and sweetener (e.g. lemon flavor, xylitol): q.s.

[0077] pH adjuster (e.g. phosphate buffer): q.s.

[0078] Water: q.s.

[0079] The mass ratio of the goldberry brick tea extract to the L. reuteri DSM 17938 fermentation liquor is 1:3.

[0080] Preparation:

[0081] The goldberry brick tea extract is prepared according to Example 1.

[0082] The preparation condition of the L. reuteri DSM 17938 fermentation liquor is adjusted to anaerobic fermentation at 37°C for 36 hours, and the remaining steps are the same as in Example 1.

[0083] Compounding: mix the extract and the fermentation liquor, add sodium hyaluronate, zinc ions, abrasives, humectants, surfactants, flavors and sweeteners, adjust the pH to 7.0, add water to a total amount of 100%, stir uniformly, and then fill into a gel.

[0084] Example 3:

[0085] A kind of goldberry brick tea extract and probiotic compound oral ulcer repair composition, including the following components by mass percentage:

[0086] Goldberry brick tea extract: 5%

[0087] Probiotic fermentation liquor (Lactobacillus reuteri DSM 17938): 15%

[0088] Sodium hyaluronate: 0.8%

[0089] Zinc ions: 0.15%

[0090] Abrasive (e.g. calcium hydrogen phosphate): 20%

[0091] Humectant (e.g. polyethylene glycol): 30%

[0092] Surfactant (e.g. sodium lauryl sulfate): 2%

[0093] Flavor and sweetener (e.g. strawberry flavor, sucralose): q.s.

[0094] pH adjuster (e.g. sodium bicarbonate solution): q.s.

[0095] Water: q.s.

[0096] The mass ratio of the goldberry brick tea extract to the L. reuteri DSM 17938 fermentation liquor is 1:3.

[0097] Preparation:

[0098] Goldberry brick tea extract preparation: the solid-liquid ratio is adjusted to 1:25 (g / mL), and the enzymolysis time is extended to 3 hours, and the rest of the extraction steps are the same as in Example 1.

[0099] L. reuteri DSM 17938 fermentation liquor preparation is the same as in Example 1.

[0100] Compounding: mix the extract and the fermentation liquor, add sodium hyaluronate, zinc ions, a friction agent, a humectant, a surfactant, a flavoring agent and a sweetener, adjust the pH to 6.5, add water to a total amount of 100%, and then stir uniformly to fill into a spray.

[0101] The present application also provides a preparation method of a goldberry brick tea extract and probiotic compound oral ulcer repair composition, comprising the following steps:

[0102] Step one, goldberry brick tea extract preparation: including enzymolysis, ultrasonic extraction, purification and other steps, the specific steps are as follows:

[0103] Enzymolysis: the goldberry brick tea is added with a mixed solution of cellulase and pectinase at a solid-liquid ratio of 1:20 (g / mL) and is subjected to enzymolysis at 50°C for 2 hours. The cellulase and pectinase can destroy the cell wall structure of the goldberry brick tea, so that the effective components in the cells are more easily released.

[0104] Ultrasonic extraction: the mixture after enzymolysis is subjected to 40 kHz ultrasonic treatment for 45 minutes, and then is filtered to obtain a crude extract. The ultrasonic extraction utilizes the cavitation effect and mechanical effect of ultrasonic waves to further destroy the cell structure, promote the dissolution and diffusion of the effective components, and improve the extraction efficiency.

[0105] Purification: the crude extract is adsorbed by a macroporous resin, eluted with 50% ethanol, concentrated and dried to obtain an extract, and the content of dihydromyricetin in the extract is ensured to be ≥20%. The macroporous resin adsorption purification technology can selectively adsorb the effective components in the extract, remove impurities, and improve the purity and quality of the extract.

[0106] Step two, L. reuteri DSM 17938 fermentation liquor preparation:

[0107] L. reuteri DSM 17938 was inoculated into MRS medium and fermented under anaerobic conditions at 37°C for 48 hours. MRS medium is a culture medium suitable for the growth of lactic acid bacteria, which can provide sufficient nutrients for L. reuteri DSM 17938, promote its growth and reproduction, and produce metabolites.

[0108] After fermentation, the fermentation broth was centrifuged at 8000 rpm for 15 minutes, and the supernatant was taken and filtered to remove bacteria to obtain the fermentation broth. The centrifugation and filtration steps can remove the bacteria and impurities in the fermentation broth to obtain pure probiotic fermentation broth.

[0109] Step three, compounding process:

[0110] In a suitable container, first mix water and humectant evenly.

[0111] Add the rubbing agent and slowly stir until evenly dispersed.

[0112] Add the goldberry brick tea extract, probiotic fermentation broth, sodium hyaluronate, and zinc ions in sequence, and continue stirring until completely dissolved.

[0113] Add the surfactant, flavor, and sweetener, adjust the pH to 6.5-7.0, and finally add water to adjust to the desired total amount. After stirring evenly, fill the container.

[0114] Experimental data and effect verification:

[0115] (1) Antibacterial experiment

[0116] 1. Method: Paper disc diffusion method was used to test the antibacterial effect of the composition on Streptococcus mutans (a common oral pathogenic bacterium). Paper discs containing a certain concentration of the composition were placed on the surface of the culture medium coated with S. mutans, and after incubation under suitable conditions for a certain period of time, the diameter of the inhibition zone was measured.

[0117] 2. Results: The diameter of the inhibition zone was ≥18 mm, which was 30% higher than that of the single extract (no relevant data was disclosed in the existing patent). This indicates that the composition of the present application has stronger antibacterial effect and can effectively inhibit the growth and reproduction of oral pathogenic bacteria, providing strong protection for the treatment and prevention of oral ulcers.

[0118] (2) Animal model

[0119] 1. Method: The healing time of the composition and single extract was compared in a rat oral ulcer model. The rat oral ulcer was induced by chemical method, and then the composition and single extract were administered for treatment, and the healing time of the ulcer was observed and recorded.

[0120] 2. Results: The composition group shortened the healing time by 40%, and the mucosa repair speed was significantly improved. This shows that the composition of the present application can accelerate the healing process of oral ulcer and promote mucosa repair, and its therapeutic effect is obviously better than that of single extract.

[0121] (III) Clinical data

[0122] 1. Sample size: 200 cases of oral ulcer patients were selected and randomly divided into experimental and control groups, 100 cases in each group.

[0123] 2. Results: The experimental group used the composition of the present application for treatment, and the control group used the existing patent (CN1130198C) therapeutic agent for treatment. After 6 months of follow-up observation, the 6-month recurrence rate of the experimental group was reduced to 15% (see Table 1), while the control group did not provide long-term recurrence rate data. This shows that the composition of the present application has better long-term efficacy and can effectively reduce the recurrence rate of oral ulcer.

[0124] Table 1 Comparison of the present application and prior art

[0125]

[0126] The main innovations of the present application are as follows:

[0127] 1. Compound ratio: The mass ratio of the goldberry brick tea extract and the probiotic fermentation broth is 1:1-1:3, which is the best ratio determined through a large number of experimental studies, and can make the two main components play the best synergistic effect and improve the therapeutic effect of the composition; The goldberry brick tea extract has the effect of quickly relieving inflammation and pain, and can quickly relieve the pain and inflammatory reaction caused by oral ulcer; the probiotic metabolites (such as bacteriocin) have the function of promoting mucosa repair and can accelerate the healing of the ulcer surface; the two have synergistic effect from the aspects of anti-inflammatory and repair to treat oral ulcer, and improve the therapeutic effect.

[0128] 2. Strain specificity: L. reuteri DSM 17938 strain is limited to use, which has specific biological characteristics and functions, can effectively colonize in the oral cavity and play the role of regulating microecology and inhibiting pathogenic bacteria, and has obvious advantages compared with other strains.

[0129] 3. Toothpaste dosage form design: combined with abrasives, humectants and other auxiliary materials, a toothpaste form suitable for daily use is designed, while the biological activity and stability of the compound composition are maintained.

[0130] The above merely illustrates the specific embodiments of the present application, but the protection scope of the present application is not limited thereto, any changes or replacements within the technical scope disclosed by the present application, which can be easily thought by any person skilled in the art, should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A compound oral ulcer repair composition consisting of goldenberry brick tea extract and probiotics, characterized in that, It includes the following components by mass percentage: Goldenberry Fu brick tea extract: 5%-20%; Probiotic fermentation broth: 5%-30%; Sodium hyaluronate: 0.1%-1%; Zinc ions: 0.05%-0.2%; Friction agent: 20%-40%; Wetting agent: 10%-30%; Surfactant: 1%-2%; The remainder consists of pharmaceutically acceptable excipients, including flavorings and sweeteners, pH adjusters, and water.

2. The oral ulcer repair composition of goldenberry tea extract and probiotics as described in claim 1, characterized in that: The content of dihydromyricetin in the Golden Berry Brick Tea Extract is ≥25%.

3. The oral ulcer repair composition of goldenberry brick tea extract and probiotics as described in claim 1, characterized in that: The probiotic fermentation broth contains Lactobacillus reuteri DSM 17938, with a viable count ≥1×10⁻⁶. 8 CFU / g.

4. The oral ulcer repair composition of goldenberry tea extract and probiotics as described in claim 1, characterized in that: The mass ratio of the goldenberry brick tea extract to the probiotic fermentation liquid is 1:1 to 1:

3.

5. The oral ulcer repair composition of goldenberry brick tea extract and probiotics as described in claim 1, characterized in that: The friction agent includes one or a mixture of several of the following: silica, calcium carbonate, and dicalcium phosphate.

6. The oral ulcer repair composition of goldenberry brick tea extract and probiotics as described in claim 1, characterized in that: The wetting agent includes one or a mixture of several of glycerin, sorbitol, and polyethylene glycol.

7. The oral ulcer repair composition of goldenberry brick tea extract and probiotics as described in claim 1, characterized in that: The surfactant includes one or a mixture of several of sodium dodecyl sulfate, cocamidopropyl betaine, and sodium lauryl sulfate.

8. The oral ulcer repair composition of goldenberry brick tea extract and probiotics as described in claim 1, characterized in that: The flavorings include one or a mixture of menthol, lemon essence, and strawberry essence.

9. The oral ulcer repair composition of goldenberry brick tea extract and probiotics as described in claim 1, characterized in that: The sweetener includes one or a mixture of several of sucrose, xylitol, and sucralose.

10. A method for preparing a compound oral ulcer repair composition of goldenberry brick tea extract and probiotics, characterized in that, Includes the following steps: Step 1: Preparation of Golden Brick Tea Extract: This includes enzymatic hydrolysis, ultrasonic extraction, and purification steps, as detailed below: Enzymatic hydrolysis: Add the Jinmei Fuzhuan tea to a mixture of cellulase and pectinase at a material-to-liquid ratio of 1:20, and enzymatically hydrolyze for 2 hours at 50℃. Ultrasonic extraction: The enzymatically hydrolyzed mixture was subjected to ultrasonic treatment at 40 kHz for 45 minutes, and then filtered to obtain a crude extract; Purification: The crude extract was adsorbed through a macroporous resin, eluted with 50% ethanol, concentrated and dried to obtain the extract, ensuring that the dihydromyricetin content in the extract was ≥20%; Step 2: Preparation of L. reuteri DSM 17938 fermentation broth: L. reuteri DSM 17938 was inoculated into MRS medium and fermented under anaerobic conditions at 37°C for 48 hours; After fermentation, the fermentation broth was centrifuged at 8000 rpm for 15 minutes, the supernatant was collected, and the broth was filtered to remove bacteria to obtain probiotic fermentation broth. Step 3, Compounding Process: In a suitable container, first mix the water and wetting agent thoroughly; Add the abrasive and stir slowly until evenly dispersed; Add the Golden Berry Brick Tea Extract, Probiotic Fermentation Liquid, Sodium Hyaluronate, and Zinc Ions in sequence, and continue stirring until completely dissolved; Add surfactants, flavorings, and sweeteners; adjust the pH to 6.5-7.0; finally, add water to adjust the total volume to the required level; stir well before filling; the contents include the following components by weight percentage: Goldenberry Fu brick tea extract: 5%-20%; Probiotic fermentation broth: 5%-30%; Sodium hyaluronate: 0.1%-1%; Zinc ions: 0.05%-0.2%; Friction agent: 20%-40%; Wetting agent: 10%-30%; Surfactant: 1%-2%; The remainder consists of pharmaceutically acceptable excipients, including flavorings and sweeteners, pH adjusters, and water.

Images