CN111514161B

CN111514161B - Anti-oral ulcer preparation and application thereof

Info

Publication number: CN111514161B
Application number: CN202010466888.3A
Authority: CN
Inventors: 李秋雁; 徐志良; 张咪
Original assignee: Jiangsu Xuebao Daily Chemical Co ltd
Current assignee: Jiangsu Xuebao Daily Chemical Co ltd
Priority date: 2020-05-28
Filing date: 2020-05-28
Publication date: 2021-05-04
Anticipated expiration: 2040-05-28
Also published as: CN111514161A

Abstract

The invention discloses an anti-oral ulcer preparation which is characterized by comprising the following components in percentage by mass: the cuttlebone polysaccharide 1 accounts for 80-90%, the lactobionic acid accounts for 2-20%, the calcium salt accounts for 0.05-1%, and the plant preservative accounts for 0.5-1%. The anti-canker sore preparation can be used for preparing products for treating canker sore, such as film, ointment, powder, granules, toothpaste, mouthwash, mouth spray and the like. The invention takes marine organism polysaccharide cuttlebone polysaccharide 1 as a main mucous membrane repairing component, relieves inflammatory reaction, and promotes healing of ulcer tissues and repairing of sore surfaces; lactobionic acid and calcium salt, which play a role in buffering and synergism in the repair process; the natural plant-derived preservative is mild and safe, and has no stimulation or anaphylactic reaction.

Description

Anti-oral ulcer preparation and application thereof

Technical Field

The invention belongs to the technical field of oral care, and particularly relates to an anti-oral ulcer preparation capable of relieving oral ulcer and application thereof.

Background

Recurrent oral ulcer is one of the most common oral mucosa diseases, early pathological manifestations are mucosa edema, then epithelial blisters are generated, and dissolution, mucosa ulceration and necrosis are gradually generated to prevent shedding, so that superficial ulcer is formed. The blood vessels at the ulcer are congested and dilated, cellulose exudation appears, a large amount of inflammatory cells infiltrate, and pseudomembranous or necrotic tissues are formed at the focus. The focus can be self-healed in 10-14 days, and no scar is formed generally.

Recurrent oral ulcer has certain periodicity and is easy to recur, the pathogenic reason is not clear at present, and the recurrent oral ulcer can be related to a plurality of factors such as vitamin and trace element deficiency, immunologic function reduction, bacterial infection, local trauma, digestive system diseases and the like. At present, traditional Chinese medicine, western medicine or Chinese and western medicine are adopted for combined treatment, the traditional Chinese medicine is usually used for clearing away heat and toxic materials, promoting tissue regeneration and healing sores, the western medicine is usually used for resisting bacteria, diminishing inflammation and relieving pain, the frequency of ulcer occurrence can be reduced, the severity of ulcer occurrence can be relieved, an ideal method for preventing recurrence is not provided, and the method is worthy of further research and exploration.

The marine polysaccharide derived from marine animals, plants and microorganisms has the biological activities of enhancing immunity regulation, reducing blood sugar, regulating blood fat, resisting virus, resisting tumor, resisting blood coagulation, resisting aging, resisting inflammation and the like, and has wide application prospects in the fields of food, daily chemicals, medicines and the like. The cuttlebone polysaccharide 1 is a natural active polysaccharide derived from cuttlebone of a marine traditional Chinese medicine, has the effects of resisting oxidation and improving the levels of Epidermal Growth Factor (EGF) and platelet-derived growth factor (PDGF), and has fewer application researches in the oral cavity field.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide a mild and non-irritant oral ulcer resisting preparation which can relieve inflammatory reaction, promote healing of ulcer tissues and repair of sore surfaces and is application thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

the anti-oral ulcer preparation is characterized by comprising the following components in percentage by mass: the cuttlebone polysaccharide 1 accounts for 80-90%, the lactobionic acid accounts for 2-20%, the calcium salt accounts for 0.05-1%, and the plant preservative accounts for 0.5-1%.

Under pathological conditions such as chronic inflammation and tumor, the expression of tumor necrosis factor-a (TNF-a) is increased. The increase of TNF-a of patients with recurrent oral ulcer can promote the release of various chemokines, oxygen free radicals, elastin and the like, further aggravate tissue lysis, edema and ulceration and cause tissue structural damage. After TNF-a is increased, inflammatory factors such as TNF-a and interleukin-6 (IL-6) are activated to generate, the content of IL-6 of a recurrent oral ulcer patient is increased, cell proliferation and differentiation and apoptosis are stimulated, and the TNF-a and the IL-6 interact to aggravate oral ulcer symptoms. The cuttlebone polysaccharide 1 can improve the activity of superoxide dismutase, clear away oxygen free radicals, relieve the injury of mucosal cells and adjust the inflammatory reaction of mucosal injury; meanwhile, the composition stimulates epidermal growth factors, reduces the generation of TNF-a, relieves inflammatory symptoms and promotes the repair and healing of ulcer surfaces.

Lactobionic acid has strong oxidation resistance, can chelate iron ions, reduces the damage of hydroxyl radicals generated by ion catalysis to tissues, and strengthens wound repair.

It is further characterized in that: the calcium salt is calcium carbonate or calcium gluconate. The calcium salt can form a high-permeability state in interstitial fluid after being applied to the ulcer surface, so that the fibrin is precipitated and the cell division and proliferation are promoted, thereby accelerating the healing of the ulcer surface.

Preferably: the plant preservative is a zanthoxylum bungeanum maxim extract or a forsythia suspensa maxim extract. The fructus zanthoxyli extract contains active ingredients such as limonene, cumic alcohol, dragon's geraniol, phytosterol, benzoic acid, unsaturated organic acid, diosmin and alkaloid, and the fructus forsythiae extract contains active ingredients such as hypericin, triterpenoid saponin, phytosterol, forsythol, alkaloid, saponin, oleanolic acid and coumarins, and the active ingredients can easily penetrate through a cell membrane structure to interfere the permeability of a microbial cell membrane and hinder the absorption of the cell membrane to amino acid, so that the physiological activity of the microbe is disordered, and the antibacterial effect is achieved. The extracts of the wild pepper fruits and the forsythia suspense which are natural plant sources cooperate with each other to resist bacteria, have no stimulation to mucous membranes, and are safe and mild.

The anti-canker sore preparation can be used for preparing products for treating canker sore, such as film, ointment, powder, granules, toothpaste, mouthwash, mouth spray and the like.

The toothpaste adopting the anti-canker sore preparation has no adverse reaction in the using process. Compared with the toothpaste of a control group, the toothpaste of a test group has obvious difference (p is less than 0.05) in the healing time and the recurrence frequency of the ulcer, and the toothpaste of the test group has clinical effects of promoting the healing of the ulcer and reducing the recurrence frequency of the ulcer.

Compared with the prior art, the invention has the advantages that: the invention takes marine organism polysaccharide cuttlebone polysaccharide 1 as a main mucous membrane repairing component, relieves inflammatory reaction, and promotes healing of ulcer tissues and repairing of sore surfaces; lactobionic acid and calcium salt, which play a role in buffering and synergism in the repair process; the natural plant-derived preservative is mild and safe, and has no stimulation or anaphylactic reaction.

Detailed Description

The present invention will be described in further detail with reference to examples, which are provided for illustration only and are not intended to limit the scope of the present invention. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.

Example 1

1. Preparation of cuttlebone polysaccharide 1

Weighing a certain amount of cuttlebone powder with the granularity of 80-100 meshes, and adding the cuttlebone powder into a sodium acetate solution with the pH of 6.5 to ensure that the material-liquid ratio is 1: 30, of a nitrogen-containing gas; heating to 55 deg.C, adding papain for enzymolysis for 4 hr with enzyme amount of 4%; after enzymolysis, quickly heating to 90 ℃, and inactivating enzyme for 10 min; centrifuging at 8000r/min for 10min, adding ethanol into the supernatant, precipitating with ethanol overnight, centrifuging, and freeze drying the supernatant to obtain Os Sepiae crude polysaccharide; dissolving Os Sepiae crude polysaccharide with distilled water, separating and purifying with ion exchange gel column and molecular sieve gel column, and freeze drying the obtained collected solution to obtain Os Sepiae polysaccharide-1.

2. Preparation of anti-oral ulcer preparation

Adding 80% of cuttlebone polysaccharide-1, 15% of lactobionic acid, 0.5% of calcium carbonate/calcium gluconate and 1% of zanthoxylum fruit extract/fructus forsythiae extract into a high-speed mixer in percentage by mass, fully and uniformly mixing, standing in a granulator for 8-15min, drying and cooling to obtain the anti-oral ulcer preparation.

3. Preparation of toothpaste containing dental ulcer preparation

(1) Sterilization

Adding a certain amount of pure water and water-soluble materials (saccharin sodium and sodium dihydrogen phosphate) into a sterilizing pot, stirring to dissolve, and sterilizing.

(2) Premixing

Adding a certain amount of humectants such as sorbitol and glycerol into a premixing pot.

(3) Powder feeding

Adding 10% of the anti-canker sore preparation into a homogenizing container, starting a vacuum pump matched with the homogenizing container, and sucking the materials in a sterilizing pot and a premixing pot into the homogenizing container; sucking powder (anti-canker sore preparation, hydroxypropyl guar gum, cellulose gum, xanthan gum, hydrated silica and calcium hydrophosphate) into a corresponding homogenizing container by using a vacuum pump (the vacuum degree P is approximately equal to-0.06 MPa); and after powder suction is finished, controlling the vacuum degree P to be-0.06 MPa to-0.09 MPa and the temperature T to be less than 40 ℃, quickly stirring for about 20min, and stopping stirring after stirring is finished.

(4) Stirring the mixture

Sucking sodium lauroyl sarcosinate, cocamidopropyl betaine, hydrated silica and calcium hydrophosphate into corresponding homogenizing containers by using a vacuum pump (the vacuum degree P is approximately equal to-0.06 MPa); after the powder is sucked, controlling the vacuum degree P between-0.06 MPa and-0.09 MPa and the temperature T less than 40 ℃, and quickly stirring for about 20 min.

(5) Degassing of gases

After stirring, controlling the vacuum to be 0.07MPa and the temperature T to be less than 40 ℃, and sucking the essence into a homogenizing container by using a vacuum pump. After the addition of the essence, the mixture was homogenized and degassed for 20 minutes (from the moment when the essence vacuum reaches the maximum) and the preparation was complete.

4. Evaluation of clinical efficacy of toothpaste containing oral ulcer preparation in relieving light recurrent aphthous ulcer

Subjects were interviewed back at baseline, 4 weeks, 8 weeks for oral condition assessment using a randomized double-blind parallel control design.

(1) Grouping tests: subjects were randomized into two groups, 36 subjects in the test group and 35 subjects in the control group.

(2) The using method comprises the following steps: the subjects brushed their teeth 2 times per day for at least 2 min. During the ulcer attack, the subject needs three meals and then rinses with clear water, the toothpaste is smeared on the affected part, and the mouth is rinsed after 5 min. Subjects were able to use only the indicated test toothpastes, and prohibited the use of other therapeutic agents that promote ulcer healing, including VC and the like. The test toothpaste is used on site when the subject visits for the first time, the teeth are brushed and the affected part is smeared once as required, and the change of the pain index is recorded.

(3) Test results

Comparing two groups of base lines

The distribution of the sex and the ulcer positions of the test group subjects and the control group subjects is balanced, and the difference has no statistical significance; the age, number of ulcers, time to ulcer appearance when included in the study, baseline pain values, allergic history and differences in dietary habits were not statistically significant for the patients in the test and control groups, see table 1.

TABLE 1 Baseline comparison

② clinical effects

Compared with the healing time and the recurrence frequency of the ulcer of a control group, the difference of the test group and the control group has statistical significance; the differences in pain values after use were not statistically significant in the test and control groups, see table 2. Adverse reactions did not occur in the test process of all the subjects, and the incidence rate of the adverse reactions was 0%.

TABLE 2 evaluation of clinical Effect

Evaluation index	Test group	Control group	Statistical value	P value
					Healing time (Tian)	5.66±2.02	7.46±2.69	t＝3.11	0.0027
Frequency of recurrence (times)	3.06±1.48	4.40±2.89	t＝2.42	0.0189
					Pain value after use	3.00±1.66	2.66±1.51	t＝-0.91	0.3661

Compared with the toothpaste of a control group, the toothpaste of a test group has obvious difference (p is less than 0.05) in the healing time and the recurrence frequency of the ulcer, and the toothpaste of the test group has clinical effects of promoting the healing of the ulcer and reducing the recurrence frequency of the ulcer.

Claims

1. The preparation for relieving oral ulcer is characterized by comprising the following components in percentage by mass: the composition comprises 80-90% of cuttlebone polysaccharide 1, 2-20% of lactobionic acid, 0.05-1% of calcium salt and 0.5-1% of plant preservative, and the preparation is applied to toothpaste or mouthwash.

2. The oral ulcer-reducing formulation of claim 1, wherein: the calcium salt is calcium carbonate or calcium gluconate.

3. The oral ulcer-reducing formulation of claim 1 or 2, wherein: the plant preservative is a zanthoxylum bungeanum maxim extract or a forsythia suspensa maxim extract.