阅读说明：本技术 一种活性多肽-pdrn组合物及其在制备护理产品中的应用 (Active polypeptide-PDRN composition and application thereof in preparation of nursing products ) 是由 姬胜利 王盈盈 殷金岗 于 2021-07-14 设计创作，主要内容包括：本发明涉及一种活性多肽-PDRN组合物及其在制备护理产品中的应用,本发明提供了一种活性多肽-PDRN组合物,通过与基质类物质配合能够起到抑制口腔溃疡和幽门螺杆菌引起的胃溃疡。解决了现有技术中口腔溃疡易复发、难治愈的问题,既能促进已形成的口腔溃疡愈合,又能有效预防细菌性胃溃疡的复发,可以从根本上清除口腔中的幽门螺杆菌、有效降低细菌性胃溃疡的复发。本发明产品以阳离子抗菌肽、PDRN和抗炎修复肽为主要功效成分,生物相容性好,对人体安全无毒,同时提供其制备和应用方法。本发明广泛应用于预防和治疗溃疡药物技术领域。(The invention relates to an active polypeptide-PDRN composition and application thereof in preparation of a nursing product, and provides the active polypeptide-PDRN composition which can inhibit oral ulcer and gastric ulcer caused by helicobacter pylori by matching with a matrix substance. Solves the problems of easy relapse and difficult healing of the oral ulcer in the prior art, can promote the healing of the formed oral ulcer, can effectively prevent the relapse of the bacterial gastric ulcer, can fundamentally eliminate helicobacter pylori in the oral cavity, and effectively reduce the relapse of the bacterial gastric ulcer. The product of the invention takes the cationic antibacterial peptide, PDRN and the anti-inflammatory repair peptide as main functional components, has good biocompatibility and is safe and nontoxic to human bodies, and simultaneously provides preparation and application methods thereof. The invention is widely applied to the technical field of the medicines for preventing and treating the ulcer.)

1. An active polypeptide-PDRN compound, which is a compound of antibacterial peptide and PDRN.

2. The active polypeptide-PDRN complex of claim 1, wherein the antimicrobial peptide is preferably a cationic antimicrobial peptide, preferably the cationic antimicrobial peptide is one or a combination of several selected from the group consisting of but not limited to protamine, pexiganan, antimicrobial peptide LL37, defensin HNP 1.

3. The active polypeptide-PDRN complex of claim 1, wherein said complex of antibacterial peptide and PDRN is prepared by the following method: mixing the antibacterial peptide solution and the PDRN solution in proportion, stirring for 0.8-1.2 hours at room temperature, and standing for 0.8-1.2 hours at room temperature;

preferably, the preparation method further comprises a step of drying the mixed solution, wherein the drying is preferably freeze drying;

further, the antibacterial peptide-PDRN compound is a protamine-PDRN compound, and the protamine and the PDRN are mixed according to the mass ratio of 0.5-1.5: 0.5-1.5;

further, the antibacterial peptide-PDRN compound is a pexiganan-antibacterial peptide LL 37-protamine-PDRN compound, and the mass ratio of the pexiganan to the antibacterial peptide LL37 to the protamine to the PDRN is 0.5-1.5: 1.5-4.5;

further, the antibacterial peptide-PDRN compound is a pexiganan-antibacterial peptide LL 37-defensin HNP 1-protamine-PDRN compound, and the mass ratio of the pexiganan to the antibacterial peptide LL37 to the defensin HNP1 to the protamine to the PDRN is 0.5-1.5: 2-6.

4. A composition comprising an active polypeptide-PDRN complex according to any one of claims 1 to 3, and further comprising an anti-inflammatory repair peptide;

preferably, the anti-inflammatory repair peptide is one or a combination of several of palmitoyl tetrapeptide-7, palmitoyl tripeptide-1, tripeptide-1 and copper peptide.

5. The composition of claim 4, further comprising other active ingredients and matrix ingredients;

preferably, the other active ingredients include but are not limited to whitening ingredients, moisturizing ingredients, oil control ingredients, anti-aging ingredients and the like;

further, the whitening component comprises glutathione, kojic acid, tranexamic acid, salicylic acid, nicotinamide, tartaric acid, azelaic acid, vitamin A and derivatives thereof, and vitamin C;

further, the moisturizing component is selected from the group consisting of, but not limited to, glycerin, hyaluronic acid, sodium pyrrolidone carboxylate, natural moisturizing factors, ceramides, collagen, lactic acid, urea, crustacean derivatives, aloe, seaweed extract, polyglutamic acid, jojoba oil, squalene, shea butter;

further, the oil control component is selected from the group consisting of, but not limited to, zinc oxide, zinc sulfate, aluminum chloride, aluminum sulfate, tannic acid, citric acid, lactic acid, vitamin B6, estradiol, estrone, ethinyl estradiol, salicylic acid, tartaric acid;

further, the anti-aging ingredients include, but are not limited to, vitamin E, vitamin C, peptide, grape polyphenol, tea polyphenol, pomegranate polyphenol, red wine polyphenol, ursolic acid, nicotinic acid, hyaluronic acid;

or the matrix component is one of an oily raw material, a powdery raw material and a colloid raw material, and also comprises a surfactant and a humectant;

preferably, the matrix component is one or a combination of glyceryl stearate, cetearyl alcohol, PEG-100 stearate, stearic acid, betaine, potassium sorbate, sodium citrate, glycerin, mint, indigo naturalis, licorice and herba schizonepetae.

6. Use of an active polypeptide-PDRN composition according to any of claims 1 to 3 and/or a composition according to claim 4 or 5 for the preparation of a care product;

preferably, the care product is a care product for the skin surface or oral cavity of a human body, and is specifically one of a liquid preparation, an emulsion, an ointment, a powder, a gel or a spray.

7. Use of an active polypeptide-PDRN composition according to any of claims 1 to 3 and/or a composition according to claim 4 or 5 for the preparation of an antibacterial product;

preferably, the antibacterial product is a product for resisting helicobacter pylori; further, the product is one of the group including, but not limited to, a medicament, a mouthwash, a mouthspray, and a toothpaste.

8. An oral care product comprising an active polypeptide-PDRN complex according to any of claims 1 to 3, an anti-inflammatory repair peptide or a composition according to claim 4 or 5.

9. The oral care product of claim 8, wherein the oral care product consists of composition a and composition B;

the composition A at least comprises 2-5% of glyceryl stearate, 1-3% of cetearyl alcohol, 0.5-1.5% of PEG-100 stearate, 1-3% of stearic acid, 1-3% of betaine, 0.1-1% of potassium sorbate, 0.1-0.5% of sodium citrate and 4-6% of glycerol;

the composition B at least comprises 10-35% of mint, 7-14% of natural indigo, 20-50% of liquorice and 15-30% of schizonepeta;

further, the composition A comprises the following raw materials in parts by weight: 2-5% of glyceryl stearate, 2% of cetearyl alcohol, 1% of PEG-100 stearate, 2% of stearic acid, 2% of betaine, 0.1-1% of potassium sorbate, 0.2-0.8% of protamine, 0.001-0.2% of pexiganan, 0. 370.001-0.2% of antibacterial peptide LL, 10.001-0.2% of defensin HNP, 0.1-0.5% of sodium citrate and 5% of glycerol;

further, the composition B comprises the following raw materials in parts by weight: 0.2-1.5% of pexiganan-antibacterial peptide LL 37-defensin HNP 1-protamine-PDRN compound, 0.26-0.01% of palmitoyl tetrapeptide-70.0001, 0.01-0.01% of palmitoyl tripeptide-10.0001, 10.01-1% of tripeptide, 0.01-1% of copper peptide, 10-35% of mint, 7-14% of indigo naturalis, 20-50% of liquorice and 15-30% of schizonepeta;

further, the composition B comprises the following raw materials in parts by weight: 0.3-0.8% of protamine-PDRN compound, 0.3-0.8% of pexiganan-antibacterial peptide LL 37-defensin HNP 1-protamine-PDRN compound, 0.3-0.8% of palmitoyl tetrapeptide-70.0001-0.01%, palmitoyl tripeptide-10.0001-0.01%, tripeptide-10.01-1%, copper peptide 0.01-1%, 10-35% of mint, 7-14% of indigo naturalis, 20-50% of liquorice and 15-30% of schizonepeta.

10. The oral care product of claim 8, wherein the oral care product is used in a method comprising: the composition A and the toothpaste are used in a matched mode, the composition A with the size of rice grains and the toothpaste with the size of soybean grains are taken from the toothbrush each time, the composition A and the toothpaste are used once in the morning and at night every day, the teeth are brushed for 3-5 min each time, and then the user rinses the mouth for 1-3 min by using clear water; composition B was applied by spraying to the oral cavity.

Technical Field

The invention belongs to the technical field of oral care products, and particularly relates to an application of an active polypeptide-PDRN composition in oral care products and antibacterial products.

Background

The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.

Oral ulcer is a common ulcerative injury disease of mucous membrane at the position of lips, cheeks, soft palate or gingiva, and can heal for about one week. Recurrent oral ulceration (RAU) is characterized by periodicity, recurrence and self-limitation, with a course of disease typically ranging from one to two weeks. The pain feeling generated during the oral ulcer attack can bring great influence to daily diet, life and work, and bring great pain to the physical and mental health of patients due to high pain and recurrence rate. Dental plaque is an ecological structure of flora adhered to the surfaces of teeth and between teeth, including bacteria and fungi, and is difficult to remove by washing with water or gargling, and is liable to cause dental ulcer. Metabolic activity of the bacterial flora in dental plaque can produce bad breath, cause halitosis, and lead to dental caries and periodontal disease in severe cases. The bacterial plaque flora contains helicobacter pylori, the helicobacter pylori is an important influencing factor of repeated attacks of RAU and bacterial gastric ulcer, helicobacter pylori infection can still be detected in the oral cavity of a patient with the bacterial gastric ulcer after treatment, the probability of the oral cavity of the patient with the RAU being infected with the helicobacter pylori is obviously higher than that of a healthy person, so that the disease is not classified between the helicobacter pylori infection in the oral cavity and the gastric ulcer caused by the helicobacter pylori, and the removal of the helicobacter pylori in the oral cavity is beneficial to the treatment of the patient with the bacterial gastric ulcer and the reduction of the recurrence rate.

The small molecular polypeptide has an immunoregulation effect on cells, can regulate the expression level of cell growth factors and inflammatory factors, promote cell growth, differentiation, reconstruction and repair, enhance the immunity of organisms, and fundamentally improve and repair skin injuries, such as: palmitoyl tetrapeptide-7, palmitoyl tripeptide-1, tripeptide-1 and copper peptide have good anti-inflammatory effect. The cationic antibacterial peptide has the characteristics of good stability, wide antibacterial spectrum (gram-positive bacteria, gram-negative bacteria and fungi) and strong cell penetrating power, for example, the cationic antibacterial peptide Pexiganan, Tilapia piscidins, Epinecidin-1, Catelicidins, Defensins, Bicarinalin, Odorranain-HP, PGLa-AM1 and Bacteriocins have good capability of killing Helicobacter pylori (Review of antibacterial peptides with anti-Helicobacter pylori activity. Neshani A, et al. Helicobacter pylori, 2018.). Unlike antibiotics, the use of antibacterial peptides does not cause bacterial resistance. PDRN (polydeoxyribonucleotides), polydeoxyribonucleotides, can accelerate DNA synthesis, and have repair effects such as anti-inflammation, promotion of cell regeneration, tissue repair, and promotion of wound healing as natural skin protective and repair agents, for example, Mastelli and Prilaian baby needles. The degradation product of amino acid of the polypeptide can provide raw materials for the synthesis of biological proteins, and the degradation product of nucleotide of PDRN is beneficial to the synthesis of RNA and DNA in organisms, promotes the transcription and translation of genes, and is beneficial to the growth and development of cells at ulcer positions and tissue repair.

The main functional components of the existing products aiming at ulcer treatment and helicobacter pylori removal are antibiotics and traditional Chinese medicine extracts, such as: the patent CN103191418B uses antibiotics and various traditional Chinese medicine extracts, the patent CN109010523A uses mesenchymal stem cell culture solution and various traditional Chinese medicine components, and the patent CN106265941A, CN109999123A and CN110898158A use various traditional Chinese medicine components. Wherein, the long-term use of the antibiotic components is easy to cause the drug resistance of bacteria, the curative effect is reduced, and the curative effect can not be achieved; the animal cells have the defects of high culture difficulty and high production cost; the effective components of the traditional Chinese medicine have undefined structures, complex chemical components, low content of the effective components and undefined action mechanism, the steps of extracting the effective components from the plants are complicated, and the content and the action effect of the effective components in the traditional Chinese medicine are easily influenced by different producing areas and different year sources; the long-term use of antibiotics can easily cause drug resistance, reduce the curative effect and fail to achieve the curative effect.

Disclosure of Invention

The invention aims to overcome the defects of the prior art, and provides a medicine combination set which is simple in preparation process, clear in action, safe and free from toxic and side effects from the pathogenesis of ulcer aiming at the problems that oral ulcer is easy to relapse and difficult to treat and bacterial gastric ulcer and relapse of bacterial gastric ulcer (the disease enters from the mouth) are easily caused by oral infection of helicobacter pylori.

Based on the technical effects, the invention provides the following technical scheme:

in a first aspect of the invention, an active polypeptide-PDRN complex is provided, wherein the active polypeptide-PDRN complex is a complex of an antimicrobial peptide and PDRN.

The antibacterial peptide is preferably a cationic antibacterial peptide, and the cationic antibacterial peptide is preferably protamine, pexiganan, antibacterial peptide LL37 and defensin HNP 1.

In the prior art, active antibacterial peptides and the like are added into toothpaste to achieve a bacteriostatic effect, but helicobacter pylori has the problem of easy repetition, and the existing antibacterial peptides and combinations are difficult to achieve a thorough bacteriostatic effect. The invention conjectures that the antibacterial peptide and PDRN form a compound, and the anti-inflammatory repair peptide is added as a main active ingredient, and the compound has good antibacterial activity and can effectively inhibit helicobacter pylori through verification, thereby having good prevention and treatment effects on oral ulcer induced by the helicobacter pylori and even bacterial gastric ulcer.

The anti-inflammatory repair peptide is preferably palmitoyl tetrapeptide-7, palmitoyl tripeptide-1, tripeptide-1 and copper peptide.

The PDRN is a nucleic acid substance, and a complex of the PDRN and a cationic antibacterial peptide component still needs to be added to a daily used care product by virtue of a certain matrix.

In a second aspect of the invention, there is also provided a matrix, i.e. in the form of a composition, suitable for use in said antimicrobial peptide-PDRN complex, said composition comprising said antimicrobial peptide-PDRN complex of the first aspect or said anti-inflammatory repair peptide.

The animal oral ulcer model proves that the composition can effectively improve the ulceration phenomenon of the oral ulcer, and the skilled person can conceive the application of the composition to a care product, particularly an oral care product, and the development of an antibacterial product, particularly the prevention and treatment of helicobacter pylori, based on the conventional research thought in the field.

Accordingly, in a third aspect of the invention there is provided the use of an active polypeptide-PDRN complex of the first aspect and/or a composition of the second aspect in the manufacture of a care product.

In a fourth aspect of the invention, there is provided the use of an active polypeptide-PDRN complex of the first aspect and/or a composition of the second aspect in the manufacture of an antibacterial product.

Dental plaque, which is an ecological structure of flora firmly adhering to the surfaces of teeth and between teeth, includes bacteria and fungi, is difficult to remove by washing with water, rinsing the mouth, or daily brushing. Metabolic activity of the bacterial flora in dental plaque can produce bad breath, cause halitosis, and lead to dental caries and periodontal disease in severe cases. The bacterial colony of the dental plaque contains helicobacter pylori, which is involved in the occurrence of RAU and is one of the main influencing factors of the repeated bout of RAU. Meanwhile, the oral cavity infection helicobacter pylori has certain relevance with the gastric ulcer caused by the helicobacter pylori, and the eradication of the oral cavity helicobacter pylori is beneficial to relieving the recurrence of the bacterial gastric ulcer. In view of this, the present invention also contemplates two compositions: the composition A and the composition B are used in a matched mode together with common commercial toothpaste, the composition A with the size of rice grains and the common commercial toothpaste with the size of soybean grains are taken from a toothbrush each time, the composition A and the common commercial toothpaste are used once in the morning and at night every day, the teeth are brushed for 3-5 min each time, and then the mixture is rinsed for 1-3 min with clear water; the composition B can be sprayed on the formed oral ulcer wound surface, and can also be used as a daily prophylactic for preventing oral ulcer and bacterial gastric ulcer.

Accordingly, in a fifth aspect of the present invention, there is provided an oral care product comprising an antimicrobial peptide-PDRN complex of the first aspect, an antimicrobial peptide, an anti-inflammatory repair peptide or a composition of the second aspect. The oral care product consists of composition a and composition B; the composition A at least comprises 2-5% of glyceryl stearate, 1-3% of cetearyl alcohol, 0.5-1.5% of PEG-100 stearate, 1-3% of stearic acid, 1-3% of betaine, 0.1-1% of potassium sorbate, 0.1-0.5% of sodium citrate and 4-6% of glycerol; the composition B at least comprises 10-35% of mint, 7-14% of natural indigo, 20-50% of liquorice and 15-30% of schizonepeta.

The beneficial effects of one or more technical schemes are as follows:

(1) the invention provides a pharmaceutical composition with definite effective components, simple chemical components and definite action mechanism aiming at the pathogenesis of oral ulcer and the relevance of the recurrence of the oral ulcer and the bacterial gastric ulcer, has no toxic or side effect on human bodies, effectively eliminates oral helicobacter pylori by removing and killing dental plaque flora through cationic antibacterial peptide, has high eradication rate and low recurrence rate, and has the composite effects of regulating cell immunity, inhibiting oral mucosa inflammation and promoting ulcer healing by anti-inflammatory repair peptide and PDRN.

(2) Aiming at the problems of poor transdermal absorption effect and low bioavailability of PDRN, the invention combines a cationic antibacterial peptide molecule with positive charge and a PDRN molecule with negative charge into a compound through intermolecular electrostatic acting force, takes the cationic antibacterial peptide as a PDRN carrier, has good biocompatibility, can enhance the cell penetrability of PDRN, enhances the use effect, effectively avoids the defect that the traditional PDRN baby needle needs microneedle injection operation, and enhances the usability.

(3) The composition A in the set product provided by the invention is used together with common commercial toothpaste, so that dental plaque can be effectively removed, dental caries and periodontal disease can be prevented, and tooth health can be maintained. The composition B can effectively promote ulcer healing after being sprayed on the oral ulcer surface, and meanwhile, the composition B can prevent recurrent oral ulcer and effectively reduce the recurrence of bacterial gastric ulcer when being used during the period that the oral ulcer is not attacked.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 shows the therapeutic effect of oral ulcer in rat.

Figure 2 shows the therapeutic effect on oral ulcer in human.

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

As the background introduces aiming at the current situation that the oral care products in the prior art can not completely solve the oral ulcer and the gastric ulcer, the invention provides an active polypeptide-PDRN compound and provides the application of the active polypeptide-PDRN compound in the oral care products and the antibacterial products.

In a first aspect of the invention, an active polypeptide-PDRN complex is provided, wherein the active polypeptide-PDRN complex is a complex of an antimicrobial peptide and PDRN.

Preferably, the antibacterial peptide is preferably a cationic antibacterial peptide, and further, the cationic antibacterial peptide is one or a combination of several of protamine, pexiganan, antibacterial peptide LL37 and defensin HNP 1.

Preferably, the addition ratio of the antibacterial peptide to the PDRN is 0.5-1.5: 0.5-1.5.

Aiming at the problems of poor transdermal absorption effect and low bioavailability of PDRN, the cationic antibacterial peptide molecules with positive charges and the PDRN molecules with negative charges are combined into an antibacterial peptide-PDRN compound form for use through intermolecular electrostatic acting force. The cationic antibacterial peptide is used as a carrier of PDRN, the biocompatibility is good, the cell penetrability of PDRN can be enhanced, the use effect is enhanced, the characteristic that the traditional PDRN baby needle needs a microneedle injection operation is effectively avoided, and the usability is enhanced.

Preferably, the preparation method of the active polypeptide-PDRN complex is as follows: and mixing the active polypeptide with the PDRN solution in proportion, stirring for 0.8-1.2 h at room temperature, and standing for 0.8-1.2 h at room temperature.

Further, the preparation method further comprises a step of drying the mixed solution, wherein the drying is preferably freeze drying.

The 'room temperature' condition is not any room temperature condition, and in the technical scheme of the invention, the 'room temperature' specifically means a temperature condition of 18-25 ℃ under standard atmospheric pressure.

In some embodiments with better effects in the technical scheme, the active polypeptide-PDRN compound is a protamine-PDRN compound, and the protamine and the PDRN are mixed according to a mass ratio of 0.5-1.5: 0.5-1.5;

in some embodiments with good effects, the active polypeptide-PDRN complex is a pexiganan-antimicrobial peptide LL 37-protamine-PDRN complex, and the mass ratio of the pexiganan to the antimicrobial peptide LL37 to the protamine to the PDRN is 0.5-1.5: 1.5-4.5;

in some embodiments with good effects, the active polypeptide-PDRN complex is a pexiganan-antimicrobial peptide LL 37-defensin HNP 1-protamine-PDRN complex, and the mass ratio of the pexiganan to the antimicrobial peptide LL37 to the defensin HNP1 to the protamine to the PDRN is 0.5-1.5: 2-6.

In a second aspect of the invention, there is provided a composition comprising an active polypeptide-PDRN complex of the first aspect, and further comprising an anti-inflammatory repair peptide.

Preferably, the anti-inflammatory repair peptide is one or a combination of several of palmitoyl tetrapeptide-7, palmitoyl tripeptide-1, tripeptide-1 and copper peptide.

In the active polypeptide-PDRN complex of the first aspect, various forms of the complex are provided, and in the composition of the second aspect, the antibacterial peptide-PDRN complex of the first aspect is included in combination with an anti-inflammatory repair peptide, where the term "comprising" includes any one or more of the aspects of the first aspect.

Preferably, the composition also comprises other active ingredients and matrix ingredients.

Further, the other active ingredients include but are not limited to whitening ingredients, moisturizing ingredients, oil control ingredients, anti-aging ingredients and the like; specifically, the whitening components comprise glutathione, kojic acid, tranexamic acid, salicylic acid, nicotinamide, tartaric acid, azelaic acid, vitamin A and derivatives thereof, vitamin C and the like;

the moisturizing component is selected from glycerin, hyaluronic acid, sodium pyrrolidone carboxylate, natural moisturizing factor, ceramide, collagen, lactic acid, urea, crustacean, aloe, seaweed extract, polyglutamic acid, jojoba oil, squalene, shea butter, etc.;

the oil control component comprises but is not limited to zinc oxide, zinc sulfate, aluminum chloride, aluminum sulfate, tannic acid, citric acid, lactic acid, vitamin B6, estradiol, estrone, ethinyl estradiol, salicylic acid, fruit acid and the like;

the anti-aging component includes, but is not limited to, vitamin E, vitamin C, peptide, grape polyphenol, tea polyphenol, pomegranate polyphenol, red wine polyphenol, ursolic acid, nicotinic acid, hyaluronic acid, etc.

Further, the matrix component is one of an oily raw material, a powdery raw material and a colloid raw material, and further comprises a surfactant, a humectant and the like.

Further, the matrix component is one or a combination of glyceryl stearate, cetearyl alcohol, PEG-100 stearate, stearic acid, betaine, potassium sorbate, sodium citrate, glycerin, mint, indigo naturalis, licorice, and herba Schizonepetae.

In a third aspect of the invention there is provided the use of an active polypeptide-PDRN complex of the first aspect and/or a composition of the second aspect in the manufacture of a care product.

Preferably, the care product is a care product for the skin surface or oral cavity of a human body, and is specifically one of a liquid preparation, an emulsion, an ointment, a powder, a gel or a spray.

In a fourth aspect of the invention, there is provided the use of an active polypeptide-PDRN complex of the first aspect and/or a composition of the second aspect in the manufacture of an antibacterial product.

Preferably, the antibacterial product is a product for resisting helicobacter pylori; further, the product is one of the group including, but not limited to, a medicament, a mouthwash, a mouthspray, and a toothpaste.

In a fifth aspect of the invention, there is provided an oral care product comprising an active polypeptide-PDRN complex of the first aspect or a composition of the second aspect.

Preferably, the oral care product consists of composition a and composition B; wherein the active polypeptide-PDRN complex of the first aspect is admixed with ingredients of composition B and the cationic antimicrobial peptide is admixed with ingredients of composition A;

the composition A at least comprises 2-5% of glyceryl stearate, 1-3% of cetearyl alcohol, 0.5-1.5% of PEG-100 stearate, 1-3% of stearic acid, 1-3% of betaine, 0.1-1% of potassium sorbate, 0.1-0.5% of sodium citrate, 4-6% of glycerol and the balance of water;

the composition B at least comprises 10-35% of mint, 7-14% of natural indigo, 20-50% of liquorice, 15-30% of schizonepeta and the balance of glycerol or water.

Further, in some embodiments of the present invention, the composition a comprises the following raw materials and proportions: 2-5% of glyceryl stearate, 2% of cetearyl alcohol, 1% of PEG-100 stearate, 2% of stearic acid, 2% of betaine, 0.1-1% of potassium sorbate, 0.2-0.8% of protamine, 0.001-0.2% of pexiganan, 0. 370.001-0.2% of antibacterial peptide LL, 0.1-0.5% of defensin HNP10.001, 0.1-0.5% of sodium citrate and 5% of glycerol.

Further, in some embodiments of the present invention, the composition B comprises the following raw materials and proportions: 0.2-1.5% of pexiganan-antibacterial peptide LL 37-defensin HNP 1-protamine-PDRN compound, 0.26-0.01% of palmitoyl tetrapeptide-70.0001, 0.01-0.01% of palmitoyl tripeptide-10.0001, 10.01-1% of tripeptide, 0.01-1% of copper peptide, 10-35% of mint, 7-14% of indigo naturalis, 20-50% of liquorice and 15-30% of schizonepeta;

in other embodiments, the composition B comprises the following raw materials in parts by weight: 0.3-0.8% of protamine-PDRN compound, 0.3-0.8% of pexiganan-antibacterial peptide LL 37-defensin HNP 1-protamine-PDRN compound, 0.3-0.8% of palmitoyl tetrapeptide-70.0001-0.01%, palmitoyl tripeptide-10.0001-0.01%, tripeptide-10.01-1%, copper peptide 0.01-1%, 10-35% of mint, 7-14% of indigo naturalis, 20-50% of liquorice and 15-30% of schizonepeta.

Further, a method of using the oral care product is as follows: the composition A and the toothpaste are used in a matched mode, the composition A with the size of rice grains and the toothpaste with the size of soybean grains are taken from the toothbrush each time, the composition A and the toothpaste are used once in the morning and at night every day, the teeth are brushed for 3-5 min each time, and then the user rinses the mouth for 1-3 min by using clear water; composition B was applied by spraying to the oral cavity.

The application method can be used after oral ulcer is formed, and can be used for daily oral care for preventing oral ulcer.

In order to make the technical solutions of the present invention more clearly understood by those skilled in the art, the technical solutions of the present invention will be described in detail below with reference to specific examples and test examples.

Example 1 construction of protamine-PDRN Complex

Firstly, mixing a 30mg/L protamine solution and a 30mg/L PDRN solution, and stirring for 1h at room temperature; then standing the mixed solution for 1h at room temperature; and finally, freeze-drying the mixed solution to obtain the protamine-PDRN compound.

Example 2 construction of Pexiganan-antimicrobial peptide LL 37-protamine-PDRN Complex

Firstly, mixing a solution containing 5mg/L of pexiganan, 10mg/L of antimicrobial peptide LL37 and 10mg/L of protamine with 30mg/L of PDRN solution, and stirring for 1h at room temperature; then standing the mixed solution for 1h at room temperature; and finally, freeze-drying the mixed solution to obtain the pexiganan-antibacterial peptide LL 37-protamine-PDRN compound.

Example 3 construction of Pexiganan-antimicrobial peptide LL 37-defensin HNP 1-protamine-PDRN Complex

Firstly, mixing a solution containing 5mg/L of pexiganan, 5mg/L of antimicrobial peptide LL37, 5mg/L of defensin HNP1 and 15mg/L of protamine with a 40mg/L PDRN solution, and stirring for 1h at room temperature; then standing the mixed solution for 1h at room temperature; and finally, freeze-drying the mixed solution to obtain a pexiganan-antimicrobial peptide LL 37-defensin HNP 1-protamine-PDRN compound.

Example 4 composition A

This example provides the formulation composition of composition a, wherein the ingredients and ratios are shown in table 1.

TABLE 1 formulation composition of composition A

Sequentially adding corresponding components in sterilized purified water according to a proportion, uniformly stirring, adjusting the pH to 6-7 by using triethanolamine and lactic acid to obtain a composition A, wherein the preparation form is an ointment, and preparing the ointment according to the specific proportion shown in the table 2 according to the preparation method:

TABLE 2 formulation of composition A

Components	Specific gravity (%)
		Glycerol stearate	4
Cetostearyl alcohol	2
		PEG-100 stearate	1
Stearic acid	2
		Betaine	2
Potassium sorbate	0.6
		Protamine	0.6
Pexiganan	0.009
		Antibacterial peptide LL37	0.002
Defensin HNP1	0.005
		Citric acid sodium salt	0.3
Glycerol	5

Example 5 composition B

This example provides the formulation of composition B, wherein the ingredients and ratios are shown in table 3.

TABLE 3 formulation composition of composition B

The traditional Chinese medicine powder is used after being ground into fine powder, materials which cannot pass through a 40-mesh sieve are firstly ground by a grinder, then pass through a 200-mesh sieve, and are mixed with other raw materials in a powder mixer to obtain a composition B, the dosage form is powder, and the powder is prepared according to the preparation method and the specific proportion in the table 4:

TABLE 4 formulation composition of composition B

Example 6 composition B

This example provides the formulation of composition B, wherein the ingredients and ratios are shown in table 5.

TABLE 5 formulation composition of composition B

Components	Specific gravity (%)
		protamine-PDRN complexes	0.3～0.8
Pexiganan-antimicrobial peptide LL 37-protamine-PDRN compound	0.3～0.8
		Palmitoyl tetrapeptide-7	0.0001～0.01
Palmitoyl tripeptide-1	0.0001～0.01
		Tripeptide-1	0.01～1
Copper peptide	0.01～1
		Mint (Chinese medicine)	10～35
Indigo naturalis (Chinese medicine)	7～14
		Schizonepeta (Chinese medicine)	15～30
Licorice (traditional Chinese medicine)	20～50

The traditional Chinese medicine powder is used after being ground into fine powder, materials which cannot pass through a 40-mesh sieve are firstly ground by a grinder, then pass through a 200-mesh sieve, and are mixed with other raw materials in a powder mixer to obtain a composition B, the dosage form is powder, and the powder is prepared according to the preparation method and the specific proportion in the table 6:

TABLE 6 formulation of composition B

Components	Specific gravity (%)
		protamine-PDRN complexes	0.6
Pexiganan-antimicrobial peptide LL 37-protamine-PDRN compound	0.4
		Palmitoyl tetrapeptide-7	0.002
Palmitoyl tripeptide-1	0.001
		Tripeptide-1	0.05
Copper peptide	0.06
		Mint (Chinese medicine)	25
Indigo naturalis (Chinese medicine)	10
		Schizonepeta (Chinese medicine)	28
Licorice (traditional Chinese medicine)	Balance of

Comparative example 1 composition B

This example provides the formulation composition of composition B, differing from example 5 in that no pexiganan-antimicrobial peptide LL 37-defensin HNP 1-protamine-PDRN complex was added, only the corresponding weights of pexiganan, antimicrobial peptide LL37, defensin HNP1 and protamine were added.

Comparative example 2 composition B

This example provides the formulation composition of composition B, differing from example 6 in that protamine-PDRN and pexiganan-antimicrobial peptide LL 37-protamine-PDRN complex were not added, and only the corresponding weights of pexiganan, antimicrobial peptide LL37 and protamine were added.

Test examples

The composition A of the invention is used together with common commercially available toothpaste, the composition A with the size of rice grains and the toothpaste with the size of soybean grains are taken from a toothbrush, the product is used once every morning and evening, the teeth are brushed for 3-5 min each time, and then the product is rinsed with clear water for 1-3 min. The composition B can be used alone, and can be sprayed on ulcer surface for preventing oral ulcer and bacterial gastric ulcer.

Test example 1 bacteriostatic test

Respectively culturing Escherichia coli and Staphylococcus aureus in 3ml liquid LB culture medium test tube, culturing helicobacter pylori in 3ml liquid brain heart culture medium test tube, and respectively culturing Candida albicans, Pseudomonas aeruginosa and streptococcus in 3ml liquid broth culture medium test tube. (1) 0.2g of the product of example 4 is respectively diluted by 1ml of sterile water, filtered and respectively added into corresponding culture media; the control group was supplemented with an equal amount of sterile water. (2) 0.1ml of the corresponding bacterial solution was inoculated and cultured at 30 ℃. (3) After one day, the OD600 was measured by a uv spectrophotometer, and the inhibition rate (inhibition rate ═ blank OD 600-test OD 600)/blank OD600 × 100%) was calculated. The results show that the growth of the thalli is obviously inhibited after the product of the example 4 is added into the culture medium compared with the control group, and the bacteriostasis rate is more than 99 percent.

Test example 2 rat canker sore model

First, 100. mu.l of 50% acetic acid/water solution was sucked into a circular plastic tube having an inner diameter of 5mm by a pipette, then the plastic tube was perpendicular to the surface of the oral mucosa of 50 SD rats (body weight 200 to 250g, 25 female and male, respectively) and held for 30 seconds, then the plastic tube was taken out, the remaining acetic acid/water solution was removed with a cotton swab, and the area of the ulcer wound was measured after 24 hours. 50 rats were randomly divided into five groups (5 female and 5 male per group), one group being a blank control group and four groups being test groups. The ulcer healing was observed after 8 hours, 14 hours and 20 hours of daily application of appropriate amounts of the product of example 5 to the ulcer surface of test group 1, the product of example 6 to the ulcer surface of test group 2, the product of comparative example 1 to the ulcer surface of test group 3 and the product of comparative example 2 to the ulcer surface of test group 4, respectively, with fasting and water deprivation for 1 hour and without any treatment of the placebo group. As shown in fig. 1, the ulcer areas of the test group 1 and the test group 2 using the example 5 composition and the example 6 composition were reduced by 84.2% and 90.1%, respectively, and the ulcer areas of the test group 3 and the test group 4 using the comparative example 1 composition and the comparative example 2 composition were reduced by 57.1% and 64.2%, respectively, while the ulcer area of the blank control group was reduced by only 45.7%. It can be seen that the product of the present invention has a very good therapeutic effect on oral ulcer, and the compositions of examples 5 and 6, in which PDRN is added and the PDRN is complexed with cationic antibacterial peptide, have a better therapeutic effect on oral ulcer than those of test examples 1 and 2.

Test example 3 oral ulcer healing test

50 oral ulcer patients were randomly selected, wherein 25 men and 25 women were divided into 5 groups (5 men and 5 women per group), and the product of example 5 was used for test group 1, the product of example 6 was used for test group 2, the product of comparative example 1 was used for test group 3, the product of comparative example 2 was used for test group 4, and the product of general market was used for control group. The corresponding products were applied to the ulcer surface of each patient at 8 am, 14 am and 20 pm, respectively, and were fasted and forbidden for 1h, and the healing of the ulcer surface was observed and recorded every day. As shown in fig. 2, the ulcer healing time was significantly shortened by using the product of the present invention compared to the control group, and the compositions of examples 5 and 6, in which PDRN was added and PDRN was complexed with cationic antimicrobial peptide, had better therapeutic effects on treating canker sores and significantly reduced pain sensations compared to test examples 1 and 2, indicating that the product of the present invention has very good therapeutic effects on treating canker sores.

Test example 4 recurrent oral ulcer treatment test

30 (15 male and 15 female) recurrent oral ulcer volunteers infected with helicobacter pylori in oral cavity were randomly selected and divided into three groups (5 male and 5 female in each group), two groups were test groups and one group was control group. Test group 1 volunteers brushed their teeth in the morning and evening of each day using the product of composition a of soybean granule size example 4 and a common commercial toothpaste of soybean granule size, and sprayed the product of example 5 in the mouth at 8 am, 14 am and 20 pm, respectively, for 30 days; test group 2 volunteers brushed their teeth in the morning and evening of each day using the product of composition a of example 4 and a conventional commercial toothpaste of soybean size, and sprayed the product of example 6 in the mouth at 8 am, 14 am and 20 pm, respectively, for 30 days; while the control group was brushed with a common commercial toothpaste for 30 days only in the morning and evening of each day. After 30 days, saliva is collected from the oral cavities of three groups of volunteers respectively, and helicobacter pylori detection kits are used for detecting helicobacter pylori in the oral cavity, and the result shows that only 1 volunteer in the test group 1 detects helicobacter pylori in the oral cavity, the clearance rate reaches 90%, and oral ulcer of all volunteers does not relapse in the period; no H.pylori was detected in the oral cavity of all volunteers in test group 2, during which time no oral ulcers had recurred; in contrast, H.pylori was detected in the oral cavity of all volunteers in the control group, and 4 volunteers exhibited recurrent symptoms of oral ulcer. Collecting saliva from the oral cavities of the volunteers respectively at day 90, and detecting helicobacter pylori in the oral cavities by using a helicobacter pylori detection kit, wherein the result shows that the helicobacter pylori is detected in the oral cavities of all the volunteers in the blank control group, and 14 times of accumulated 6 volunteers generate oral ulcer; in test 1, 2 volunteers in the mouth detected helicobacter pylori again, and 2 volunteers accumulated 4 times during this period and developed oral ulcer; in test 2 group 1 volunteers re-detected H.pylori in their mouths and 1 volunteer accumulated 1 oral ulcer during this period; it can be seen that the proportion of H.pylori infection and the recurrence rate of canker sores were significantly reduced within 60 days after discontinuation of the use of composition A and composition B in test groups 1 and 2 using the product of the present invention.

Test example 5 recurrence rate of bacterial gastric ulcer

30 volunteers (15 male and 15 female) who had suffered from bacterial gastric ulcer caused by helicobacter pylori infection but still had periodic outbreaks of gastric ulcer and had detected helicobacter pylori in the oral cavity were randomly selected and divided into three groups (5 male and 5 female in each group), two groups being test groups and one control group. Test group 1 volunteers brushed their teeth in the morning and evening of each day using the product of composition a of soybean granule size example 4 and a common commercial toothpaste of soybean granule size, and sprayed the product of example 5 in the mouth at 8 am, 14 am and 20 pm, respectively, for 30 days; test group 2 volunteers brushed their teeth in the morning and evening of each day using the product of composition a of example 4 and a conventional commercial toothpaste of soybean size, and sprayed the product of example 6 in the mouth at 8 am, 14 am and 20 pm, respectively, for 30 days; while the control group was brushed with a common commercial toothpaste for 30 days only in the morning and evening of each day. The 30 volunteers respectively collect saliva from the oral cavities of the volunteers on day 60 and detect helicobacter pylori in the oral cavity by using a helicobacter pylori detection kit, and the results show that only 1 volunteer in the test group 1 and helicobacter pylori in the oral cavity of no volunteer in the test group 2 are detected, gastric ulcer does not relapse in the period of time, helicobacter pylori is detected in the oral cavities of all volunteers in the control group, and the relapse symptom of the gastric ulcer appears in 2 volunteers. On day 90, 30 volunteers were interviewed and asked for history of gastric ulcer attack, and the investigation showed that only 1 volunteer in test group 1 had recurrent gastric ulcer, no volunteer in test group 2 had recurrent gastric ulcer, and 3 volunteers in the control group had recurrent gastric ulcer.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.