CN107446018B - Peptide for promoting wound healing and application thereof - Google Patents

Abstract

The invention relates to a peptide capable of promoting wound healing and application thereof. Specifically, the invention discloses SEQ ID NO 1 and SEQ ID NO:2, alone or in combination, and a cream comprising the peptides, wherein the cream comprises in weight%: 0.0005-0.001% by weight of SEQ ID NO:1 peptide and/or SEQ ID NO:2 peptide, and 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 2.0-4.0 rose hip oil, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract and a proper amount of lauroyl arginine ethyl ester in percentage by weight. The cream provided by the invention has the effect of promoting wound healing.

Description

Peptide for promoting wound healing and application thereof

Technical Field

The present invention relates to non-natural peptides having wound healing promoting effects and their use in cosmetic and personal care compositions.

Background

To date, a wide variety of natural and synthetic peptides have found widespread use in cosmetic compositions. In general, the inclusion of peptides in cosmetics takes advantage of their functional activities, such as inhibition of enzymes, antiviral and antibacterial activities.

Chinese invention patent CN101151043 discloses compositions and methods for promoting wound healing and tissue regeneration following tissue injury in a subject, having unexpected effects in alleviating inflammation, promoting healing, reducing scarring, increasing tensile strength, and promoting regeneration of complex tissue structures, and acting after injury to various tissues such as skin and brain.

Chinese invention patent CN101375933 discloses a method for preparing levator (Plectranthus amboinicus) extract using agitation separation method, and also discloses a pharmaceutical composition comprising crude extract and/or extract of levator for treating skin disorders, including promoting wound healing in particular in diabetic patients.

Chinese invention patent CN100389776 discloses that by administering CM101 or GBS toxin extracted from group B β -hemolytic streptococcus, a method of treating a patient with a wound is provided, in particular by reducing scarring and accelerating wound healing, the types of wounds that can be treated including surface and internal wounds, the method also includes administering CM101 or GBS toxin to a surgical patient suffering from a tumor to promote wound healing and reduce the likelihood of tumor development.

Chinese invention patent CN1297356 discloses the use of enamel matrix derivatives and/or enamel matrix proteins as therapeutic or prophylactic agents, which have wound healing, antibacterial and/or anti-inflammatory activity.

Chinese invention patent CN102665723 discloses the use of an oleogel for wound healing, said oleogel comprising a non-polar liquid and a triterpene-containing powder as an oleogel-forming agent.

US patent No. 8227410 discloses VEGF-D, a novel member of the PDGF family of growth factors, wherein endothelial cell proliferation and angiogenesis are stimulated and vascular permeability is increased, as well as nucleotide sequences encoding the same, methods for its production, antibodies and other antagonists, expression in transfected or transformed host cells, pharmaceutical compositions containing the same and its use in medical and diagnostic applications.

The Chinese patent CN1579539 discloses a method for using thymosin β 15 with biological activity in tissue repair and wound healing, thymosin β 15 has the functions of promoting vascular proliferation and tissue regeneration and repair, therefore, the pharmaceutical composition containing thymosin β 15, its biological activity variant or salt with effective dose can be used for treating wounds caused by various reasons, promoting healing, and treating cardiovascular diseases and other ischemic diseases caused by insufficient blood supply.

Chinese invention patent CN103458914 discloses a wound healing composition having a class of polypeptide compounds having a polypeptide chain of 5 to 120 amino acid units per chain. The compositions comprise a pharmaceutically acceptable medium, such as an aqueous solution, suspension, dispersion, salve, ointment, gel, cream, lotion, spray or paste, for loading the polypeptide compound. Additionally, methods of applying a wound healing composition at a concentration of about 1 μ g/ml to about 100 μ g/ml for a time sufficient to heal the wound are disclosed.

The skin is the most exposed part of the body and is particularly susceptible to various injuries, the common causes being mechanical injuries (rupture, cutting, friction), physical and chemical injuries (burns, scalds, frostbite and strong acid and alkali injuries), surgical incisions, bedsores and chronic skin ulcers caused by certain diseases. The integrity of the skin is critical to the normal survival of everyone due to the important barrier and physiological effects of the skin, and any lacerations and tears require the body to react protectively. In addition to skin damage, various soft tissues and mucous membranes are also susceptible to damage, such as gastrointestinal mucosa, cornea, and the like.

Under normal conditions, the wound can be naturally repaired and healed. The process of natural healing of wounds includes: sealing the wound to limit blood loss and prevent infection; removing damaged tissue and blood clots; followed by invasion of the wound site by various types of cells in the surrounding tissue and formation of granulation and scarring; eventually reconstructing scar tissue and altering the cell population to result in complete healing of the wound. In general, the natural healing process is effective, as the wound field is smaller or the injury is less. However, the wound is affected by the physical quality, the size and severity of the wound and the presence or absence of concurrent infection of patients, and medical intervention is required for wound healing in most cases. Moreover, chronic skin ulcers resulting from some diseases, such as intractable skin ulcers resulting from diabetes, are difficult to treat. Diabetes mellitus is a common disease, mainly due to glucose metabolism disorder caused by absolute or relative deficiency of insulin, and occurs with increased blood sugar and urine sugar. At present, the incidence rate of diabetes mellitus reaches 2 percent in China. After diabetes, 30-50% of patients have skin lesions, mostly in the lower extremities with poor blood supply. Many diabetics fail to heal because of small wounds, eventually leading to amputation and even death due to infection.

Wound healing is mainly accomplished by regeneration of granulation tissue and skin tissue. From about day three, granulation tissue grew out of the bottom of the wound and penetrated deeply into the wound. Granulation tissue plays an important role in wound healing as follows: (1) resisting infection and protecting wound surface; (2) rapid organization of blood clots, necrotic tissue and other foreign bodies; (3) filling a wound or other defect. Therefore, granulation tissue is of great significance in tissue damage repair. The main components of granulation tissue are vigorous and proliferated new capillaries and proliferated fibroblasts, and inflammatory cells such as neutrophils, macrophages and the like are also contained in the granulation tissue in different amounts. Many growth factors and cytokines are initially secreted by platelets in an aggregation response and then by macrophages in response to hypoxia and lactic acidosis, and these factors can stimulate angiogenesis. As early as 2 or 3 days after injury, new capillaries began to bud from the preexisting venules and grow toward the injury, becoming clearly visible at microscopic level approximately at day 4, and the new capillaries become connected into a network. Angiogenesis is an important feature of tissue damage repair.

The regenerative repair of the epidermis and its tissues is accomplished by three processes, epithelial cell migration, cell division and epithelial differentiation. After the epithelium is damaged, the basal layer cells at the broken end of the epithelium around the defect move to the wound surface, the epithelial cells divide actively, gradually cover the surface of the wound, the epithelium is further differentiated, and the lost tissue structure and function, such as the skin can be cornified.

New drugs currently used clinically for wound healing are mainly growth factor type proteins, such as epidermal growth factor, and other proteins that regulate cell proliferation and differentiation, such as the transforming factor-B family of proteins (TGF-B). The Recombinant bovine basic fibroblast growth factor (Recombinant bovine bFGF) and the Recombinant human epidermal growth factor (Recombinant human EGF) have been approved for clinical treatment of wound healing. At present, four kinds of gene recombinant proteins including human fibroblast growth factor are in clinical three-phase experiments. Such therapeutic proteins used in wound healing therapy are expensive, unstable to storage and cumbersome to use, and the instability of the protein (proteolytic products) may lead to an unexpected inflammatory response that is toxic to the host.

Although many attempts have been made to wound-healing promoting products using peptides, their wound-healing promoting effects have not been satisfactory.

Disclosure of Invention

In order to develop a novel peptide having an effect of promoting wound healing, the present inventors have conducted intensive studies and screened peptide libraries. Finally, the present inventors have found a novel peptide having excellent wound-healing-promoting efficacy, and finally achieved the object of the present invention.

An object of the present invention is to provide a peptide having an effect of promoting wound healing.

It is another object of the present invention to provide a composition for promoting wound healing.

It is a further object of the present invention to provide a method for promoting wound healing.

To achieve the object of the present invention, in a first aspect of the present invention, there is provided a peptide selected from the group consisting of:

(i) a peptide comprising or consisting of amino acid residues as follows:

Ala-L eu-Ala-Cys-Pro-Met-Asn-Thr-His-Ala (A L ACPMNTHA) (SEQ ID NO:1, which is also referred to as "Peptide 05"), or

(ii) A peptide comprising or consisting of amino acid residues as follows:

Cys-Asn-Ala-Arg-Thr-Ser-Met-Ile-Tyr-Leu-Thr(CNARTSMIYLT)(SEQ ID NO:2)。

according to a preferred aspect of the present invention, there is provided a combination of peptides comprising the peptide combination of SEQ ID NO. 1 and SEQ ID NO. 2.

According to a second aspect of the present invention, there is provided a wound healing promoting composition comprising a peptide of SEQ id No. 1 of the present invention and a cosmetically acceptable carrier.

According to a preferred aspect of the present invention, there is provided a wound healing promoting composition comprising the amino acid sequences of SEQ ID No. 1 and SEQ ID NO:2 and a cosmetically acceptable carrier.

According to a third aspect of the present invention there is provided the use of a peptide of SEQ ID NO. 1 of the present invention for promoting wound healing.

According to a preferred aspect of the present invention, there is provided SEQ ID NO 1 and SEQ ID NO:2 for use in promoting wound healing.

The present invention also provides a cream for promoting wound healing, comprising:

(a) individual peptides or combinations of peptides of the invention;

(b) an antioxidant;

(c) a humectant;

(d) a vegetable oil;

(e) a substrate;

(f) a preservative;

(f) and purifying the water.

These and other aspects of the present invention will become apparent to those skilled in the art upon further detailed description of the invention, including exemplary embodiments and implementations.

Wound healing wounds and/or ulcers often protrude from the skin or occur on mucosal surfaces or as a result of an infarction of organs ("stroke"). Wounds may result from defects or damage to soft tissue or from underlying conditions. The regeneration of periodontal wounds produced under experimental conditions has been previously elucidated by the present inventors and they do not fall within the scope of the present invention. As used herein, the term "skin" refers to the outermost surface of the body of an animal, including a human, which includes intact or nearly intact skin as well as wounded skin. The term "mucosal membrane" refers to the intact or damaged mucosa of an animal, such as a human, which may be the oral, buccal, otic, nasal, pulmonary, ocular, gastrointestinal, vaginal, or rectal mucosa.

In the present invention, the term "wound" refers to a bodily injury that results in the disruption of the normal integrity of a tissue structure. The term also includes the terms "sore", "lesion", "necrosis" and "ulcer". In general, the term "sore" is a broad term encompassing almost all lesions including skin or mucosal surfaces, and the term "ulcer" refers to a local defect or hole in the surface of an organ or tissue resulting from the shedding of necrotic tissue. The damage is typically associated with a defect in the tissue. Necrosis is the death of tissue due to infection, injury, inflammation or infarction.

The term "wound" in this context refers to any wound (see below for wound classification) and to any particular stage in the healing process, including the stage before healing begins or even before an incision, e.g. surgery, appears (prophylactic treatment).

Examples of wounds that can be prevented and/or treated according to the invention are, for example, sterile wounds, contused wounds, incised wounds, lacerated wounds, non-penetrating wounds (i.e. wounds that are not damaging to the skin but are damaging to underlying structures), open wounds, penetrating wounds, perforated wounds, septic wounds, subcutaneous wounds, etc. Examples of sores are pressure sores, ulcers, chrome ulcers, cold sores, pressure sores, and the like. Examples of ulcers are, for example, peptic ulcers, duodenal ulcers, gastric ulcers, gout ulcers, diabetic ulcers, hypertensive ischemic ulcers, stasis ulcers, lower leg ulcers (venous ulcers), sublingual ulcers, submucosal ulcers, symptomatic ulcers, trophic ulcers, tropical ulcers, chancroid and the like, e.g. caused by gonorrhea (including urethritis, endocervitis and proctitis). The symptoms associated with wounds or sores that may be successfully treated according to the present invention are burns, anthrax, tetanus, gas gangrene, scarlet fever, erysipelas, syphilis, folliculitis, contact impetigo, bullous impetigo, and the like. There is often some degree of overlap in the use of the terms "wound" and "ulcer" and "wound" and "sore", and these terms are often used randomly. Thus, as noted above, the term "wound" is used herein to encompass the terms "ulcer," "lesion," "sore" and "infarction," the use of which is indistinguishable unless otherwise indicated.

The term "skin" is used in a broad sense and includes the epidermis layer of the skin and, in the case of more or less damaged epidermis layers of the skin, also the dermis layer of the skin. In addition to the corneal layer, the epidermal layer of the skin refers to the outer skin (epithelium) layer, and the connective tissue layer of the deep layer of the skin is called the dermis.

Since the skin is the most exposed part of the body, it is particularly susceptible to various injuries, such as cracking, cutting, rubbing, burning, frostbite or injuries caused by various diseases. Furthermore, most skin is also easily damaged accidentally. However, the integrity of the skin is critical to the normal survival of everyone due to the important barrier and physiological role of the skin, and any lacerations and tears require the body to react to protect it from further survival.

In addition to skin damage, various tissues are also damaged (e.g., soft and hard tissues). Lesions of soft tissue including mucosa and/or skin are of great relevance to the present invention.

Healing of skin or mucosal wounds requires a series of stages to result in repair or regeneration of the skin or mucosa. In recent years, regeneration and repair have been divided into two forms of healing. Regeneration is considered a biological process in which the structure and function of the missing tissue is completely renewed. Repair, on the other hand, refers to the restoration of the continuity of damaged tissue by new tissue, rather than the biological process of replication of the structure and function of the lost tissue.

The main part of wound healing is through repair, which means that the new tissue formed is structurally and chemically different from the original tissue (scar tissue). In the initial stages of tissue repair, a process that is almost always involved is the formation of a transient connective tissue at the wound site. This process is initiated by a new extracellular collagen matrix formed by fibroblasts. This new collagen matrix then serves as a support for the connective tissue during the final stages of healing. The final stage of healing for many tissues refers to the formation of scars that contain connective tissue. For tissues with regenerative properties, such as skin and bone, the final healing involves regeneration of the original tissue. Regenerated tissue also often has some scar properties, for example, thickening of the healing bone.

Under normal circumstances the body will provide a mechanism for healing injured skin or mucous membranes to restore the integrity of the skin barrier and mucous membranes. Such repair of even minor cuts or wounds can take from hours to days to weeks. However, for ulcers, healing will be very slow, possibly lasting for a long period of time, i.e. months or years.

The stages of wound healing typically include inflammation (typically 1-3 days), migration (typically 1-6 days), proliferation (typically 3-24 days) and maturation (typically 1-12 months). The healing process is a complex and precise physical process involving migration, proliferation, differentiation of various cell types, and synthesis of matrix components. Any procedure that can affect the rate of or benefit of wound healing would be of great value.

Furthermore, since almost all tissue repair has previously involved a phase of early connective tissue formation, stimulation of this and subsequent processes is also believed to improve tissue healing.

The term "clinical healing" is used herein to refer to the condition where there is no visible disruption of the tissue and only discrete signs of inflammation, such as a slight red swelling or discontinuous swollen tissue, are present. And no pain sensation when the organ is relaxed or not touched.

The types of wounds that can be treated according to the invention also include i) common wounds, e.g., surgical, traumatic, infectious, ischemic, thermal, chemical, and bullous wounds; ii) wounds, in particular for the oral cavity, such as post-extraction wounds, in particular periodontal wounds for cyst and abscess treatment, bacterial ulcers and lesions, viral or autoimmune, mechanical, chemical, thermal, infectious and lichen-like wounds; herpes ulcers, canker sores, acute necrotizing ulcerative gingivitis and burning mouth syndrome are some of the specific cases; iii) wounds of the skin such as neoplasms, burns (e.g. chemical burns, thermal burns), lesions (bacterial, viral, autoimmune), bites and surgical incisions. Another way of classifying wounds is, for example, i) small tissue loss, slight abrasion and slight bites due to surgical incisions, or, for example, ii) severe tissue defects. The latter include ischemic ulcers, bedsores, fistulas, tears, severe bites, thermal burns, and donor site injuries (soft and hard tissues) and infarctions.

Two peptides are claimed in the present invention, namely peptide (i) having SEQ ID NO:1 or peptide (ii) having SEQ ID NO: 2. When these peptides are used in a wound healing promoting composition, the inhibition provides a benefit in promoting wound healing.

Not only was it demonstrated that these two peptides each promoted wound healing, but synergistic interactions were also noted when they were used together.

As used herein, all terms are intended to have their ordinary meaning in the art unless otherwise specifically defined. The term "amino acid" is intended to include naturally occurring amino acids as well as non-naturally occurring amino acids, and broadly includes all small molecules having one carboxyl group and at least one primary or secondary amine group capable of forming a peptide bond. The term "peptide" is intended to include all molecules having at least one peptide bond, and thus includes dipeptides, tripeptides, oligopeptides and polypeptides having up to about 20 amino acid residues. The term "peptide" also includes structures other than amino acids having one or more linkers, spacers, or terminal groups.

The peptides of the invention are provided in a cosmetically acceptable carrier. The carrier may be hydrophobic or hydrophilic. Suitable hydrophobic carriers include, for example, waxy nonionic materials commonly used in cosmetics, such as esters and ethers of fatty alcohols and fatty acids, with carbon chain lengths of C4 to C22, preferably C8 to C18, most preferably C12 to C18.

Examples of fatty hydrophobic carriers include isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl lanolate, acetylated lanolin alcohol, benzoate esters of C12-C15 alcohols, cetyl octanoate, cetyl palmitate, myristyl myristate, myristyl lactate, cetyl acetate, propylene glycol dicaprylate/decanoate, decyl oleate, acetylated lanolin, heptanoic stearate, diisostearate malate, octyl hydroxystearate, isopropyl isostearate, and the like.

Suitable hydrophilic carrier solutions may be, for example, glycols and alkoxylated glycols commonly used in cosmetics, including ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, and the like.

The wound healing promoting composition may be formulated as a nutritional liquid, serum, whitening cream, lotion, serum, spray, stick, and other forms known to those skilled in the art. Creams are currently the preferred product form.

In a cosmetically acceptable carrier, the concentration of the peptide may range from 1. mu.M to 200. mu.M, preferably from 10ppb to 150. mu.M, more preferably from 20. mu.M to 100. mu.M, most preferably from 36. mu.M to 50. mu.M.

Wound healing promoting compositions typically comprise the above-described carrier solutions at a level of from about 0.01% to about 90% by weight, preferably from about 0.1% to about 50% by weight, more preferably from about 0.1% to about 20% by weight, and most preferably from about 1% to about 10% by weight.

Examples of the antioxidant include butylhydroxyanisole, dibutylhydroxytoluene, sodium hydrogensulfite, erythorbic acid and salts thereof, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, taurine, thiotaurine, hypotaurine, and vitamin E. Among them, glutathione, vitamin E and catalase are preferable. These antioxidants may be used in combination of 1 or more than 2, and are preferably a combination of glutathione and vitamin E. When the antioxidant is added to the composition for external application to the skin (for example, cream) of the present invention, the addition ratio thereof is not particularly limited, but is usually 0.001 to 6% by weight, preferably 0.01 to 3% by weight, and more preferably 0.2 to 2% by weight, based on the total amount of the composition for external application to the skin.

Examples of the humectant include amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, aspartic acid, arginine, and theanine, and derivatives thereof; polyhydric alcohols such as ethylene glycol, 1, 3-propanediol, 1, 3-butanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol, diglycerin, and polyethylene glycol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; sugar alcohols such as mannitol, sorbitol, erythritol, xylitol, and trehalose; phospholipids such as lecithin and hydrogenated lecithin; mucopolysaccharides such as sodium hyaluronate, sodium acetylhyaluronate, heparin analogues, sodium chondroitin sulfate, etc.; high molecular compounds such as collagen, elastin, keratin, chitin, chitosan, gelatin, polyglutamic acid, etc.; sodium lactate, sodium pyrrolidone carboxylate, etc.; chamomile extract, aloe vera extract, witch hazel extract, rosemary extract, thyme extract, tea extract, perilla extract, and other plant extracts. Among them, glycine, 1, 3-propanediol, dipropylene glycol, diglycerin, diethylene glycol monoethyl ether, sodium hyaluronate, sodium acetylhyaluronate, sodium pyrrolidone carboxylate, and polyglutamic acid are preferable. These moisturizers may be used in 1 kind or in combination of 2 or more kinds, and 1, 3-propanediol and sodium hyaluronate are preferred. When the moisturizing agent is added to the composition for external application to the skin (e.g., cream) of the present invention, the addition ratio is not particularly limited, but is usually 0.001 to 40% by weight, preferably 0.1 to 30% by weight, and more preferably 5 to 20% by weight, based on the total amount of the composition for external application to the skin (e.g., cream).

The vegetable oil is selected from rose hip oil, sweet almond oil, rose hip oil, jojoba oil, wheat germ oil, carrot oil, avocado oil, castor oil, avocado oil, coconut oil, palm oil, cocoa butter, palm kernel oil, soybean oil, rice bran oil, aloe oil, veronica officinalis, chenopodium album butter, shea butter, peanut oil, corn oil, macadamia nut oil, Chinese chestnut oil, seabuckthorn oil, linseed oil, passion flower oil, calendula, mango kernel oil and rose hip oil, and is preferably one or a combination of two or more of sweet almond oil, jojoba oil and rose hip oil. Preferably, the vegetable oil in the composition of the invention is rose hip oil. When the vegetable oil is added to the composition for external application to skin (e.g., cream) of the present invention, the addition ratio is not particularly limited, but is usually 0.001 to 10% by weight, preferably 0.5 to 8% by weight, and more preferably 1.0 to 8.0% by weight, based on the total amount of the composition for external application to skin (e.g., cream).

The base is selected from vegetable oils, hydrogenated vegetable oils, beeswax, insect wax, spermaceti wax, paraffin wax, vaseline, silicone, polyacrylic acid, cellulose derivatives, and the like, and may be one or two or more selected from them. Preferably, the base in the composition of the invention is petrolatum. When a base is added to the composition for external application to skin (e.g., cream) of the present invention, the addition ratio is not particularly limited, but is usually 0.001 to 10% by weight, preferably 0.5 to 8% by weight, and more preferably 1.0 to 8.0% by weight, based on the total amount of the composition for external application to skin (e.g., cream).

As preservative, it is selected from benzyl alcohol, phenethyl alcohol, phenoxyethanol and lauroyl arginine ethyl ester, preferably lauroyl arginine ethyl ester. When the antiseptic is added to the composition for external application to skin (e.g., cream) of the present invention, the addition ratio thereof is not particularly limited, but is usually 0.001 to 5% by weight, preferably 0.1 to 5% by weight, and more preferably 0.2 to 3% by weight, based on the total amount of the composition for external application to skin (e.g., cream).

Preferably, the cream of the present invention comprises 0.0005 to 0.001% by weight of the peptide of SEQ ID NO:1 peptide and/or SEQ id no:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 aloe extract, 8.0-12.0 vaseline and a proper amount of lauroyl arginine ethyl ester.

Preferably, the cream of the invention comprises 0.001 wt% of SEQ ID NO:1 peptide, 2.0-4.0 percent of glutathione, 0.5-2.5 percent of taurine, 2.0-4.0 percent of glycol, 4.0-6.0 percent of tea extract, 2.0-4.0 percent of rose hip oil, 2.0-4.0 percent of aloe extract, 8.0-12.0 percent of vaseline and a proper amount of lauroyl arginine ethyl ester.

Preferably, the cream of the invention comprises 0.001 wt% of SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 aloe extract, 8.0-12.0 vaseline and a proper amount of lauroyl arginine ethyl ester.

Preferably, the cream of the invention comprises 0.0005 wt.% of SEQ ID NO:1 peptide and 0.0005 wt% of seq id NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 aloe extract, 8.0-12.0 vaseline and a proper amount of lauroyl arginine ethyl ester.

Further, the cream of the present invention comprises in weight%:

0.0005-0.001% by weight of SEQ ID NO:1 peptide and/or SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

Still further, the cream of the present invention comprises in weight%:

0.001 wt% of SEQ ID NO:1 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

Still further, the cream of the present invention comprises in weight%:

0.001 wt% of SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

Still further, the cream of the present invention comprises in weight%:

0.0005 wt% of SEQ ID NO:1 peptide and 0.0005 wt% of SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

The instructions contained in the wound-healing promoting product of the present invention relating to the wound-healing promoting product may contain the following: effects and efficacies (e.g. promotion of wound healing), methods of application (e.g. even application to the skin, e.g. face and neck), and possible side effects, etc.

The terms and expressions which have been employed herein are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

For a more clear illustration of the invention, reference is now made in detail to the following examples, which are intended to be purely exemplary of the invention and are not to be interpreted as limiting the application.

Examples

The following examples are intended to illustrate the invention in a non-limiting manner.

Example 1

A composition for promoting wound healing comprising SEQ ID NO: 0.001 wt% of 1 peptide, 0.6 wt% of carbomer, 15 wt% of glycerol and 3 wt% of propylene glycol.

Example 2

A composition for promoting wound healing comprising SEQ ID NO: 0.001 wt% of 2 peptide, 0.6 wt% of carbomer, 15 wt% of glycerol and 3 wt% of propylene glycol.

Example 3

A composition for promoting wound healing comprising SEQ ID NO:1 peptide 0.0005 wt%, SEQ ID NO: 0.0005 wt% of 2 peptide, 0.6 wt% of carbomer, 15 wt% of glycerol and 3 wt% of propylene glycol.

Example 4

40 SPF-grade female BA L B/c mice were selected, with a 20 + -2 g mass, and randomly divided into 4 groups of 10 mice each.

Group a-control group, a composition containing 0.6 wt% carbomer, 15 wt% glycerin, 3 wt% propylene glycol, but no healing promoting active ingredient was administered;

group B-test group, applying the composition of example 1;

group C-test group, the composition of example 2 was applied;

group D-test group, the composition of example 3 was applied.

After anesthesia, the back of a mouse is subjected to hair passing, a 0.8cm × 0.8.8 cm wound surface is cut in the middle of a spine, skin and fascia are removed, a silicone splint on one side is adhered by an adhesive, a wound of a central splint and splint fixing are interrupted, 6-0 nylon threads are sewn to ensure fixed positioning, and a transparent occlusion dressing is used for covering the wound, each group is locally administrated on the wound surface 2 times a day in the morning and at night, each group is observed on days 1,3, 7 and 10 after operation, animals are killed after the day 10, and skin wound specimens are obtained.

The detection method comprises the following steps:

(1) general observation of wound surface: the general condition of the wound surface was observed on days 1,3, 7 and 10 after the injury.

(2) The influence of the medicine on the wound healing rate: calculating the wound healing rate of rats on 1 st, 3 th, 7 th and 10 th days after injury. Wherein the healing rate is (original wound area-unhealed wound area)/original wound area.

The experimental results are as follows:

(1) general observations of the wound surface: the wound repair condition between the A group and the B, C, D group is obviously different.

After surgery, a little blush appeared around the B, C, D group wounds, indicating that granulation tissue was growing, while the A group wounds were moist.

After operation, the granulation tissue of B, C, D groups grows obviously and the skin of wound edge shrinks obviously, while the wound of A group begins to appear with red halo and a small amount of granulation tissue is visible.

After 5D, B, C groups of wounds grow large-area granulation tissues, the wounds become shallow and tend to be dry, the D group of wounds are nearly dry, the wounds are basically filled with the granulation tissues, most of the wounds are healed, while the A group of wounds are wet, the granulation tissues grow obviously, and the wounds begin to heal.

After operation, the wounds in B, C groups are dry, the wound surface is basically filled with granulation tissues, most of the wounds are healed, the wound surface in the D group is basically healed, the wounds in the A group are wet, the granulation tissues grow obviously, and the wounds begin to heal.

The wound surfaces of group 10d, B, C, D healed substantially after surgery, while the wounds of group A healed only for the majority.

(2) The effect of the drug on the wound healing rate is shown in table 1.

TABLE 1 statistics of wound healing Rate

Analysis of results

No matter the general observation result of the wound surface or the statistical result of the wound surface healing rate, we can see that the wound surface healing of the mice of the three test groups is obviously earlier than that of the mice of the control group, which shows that the peptide of the invention has obvious promotion effect on the wound healing, and the mice of the test group, particularly the D group, namely the mixed peptide group, have the fastest healing speed and are obviously higher than those of the mice of the other two test groups, and when the medicine is prepared, the concentrations of the peptides used by the three test groups are the same, so that the two peptides of the invention can be judged to have obvious synergistic effect on the aspect of promoting the wound healing.

Example 5: preparation of cream

Mixing sweet almond oil, aloe extract, carbomer and rose oil, stirring, adding other components, stirring, and making into cream.

Example 6: preparation of cream

Composition (I)	Content (wt%)
		The peptides of the present invention (SEQ ID NO: 2)	0.001
Glutathione	2.0
		Taurine	2.5
1,3 propanediol	2.0
		Tea extract	6.0
Rose fruit oil	4.0
		Sweet almond oil	2.0
Aloe extract	2.0
		Carbomer	12.0
Asiaticoside	3.0
		Glucan	4.0
Tremella extract	3.0
		Soy isoflavone	2.5
Extract of zedoary turmeric	1.5
		Dendrobium officinale extract	1.5
Lauroyl arginine ethyl ester	2.0
		Purified water	Residual amount
Total of	100

Mixing sweet almond oil, aloe extract, carbomer and rose oil, stirring, adding other components, stirring, and making into cream.

Example 7: preparation of cream

Mixing sweet almond oil, aloe extract, carbomer and rose oil, stirring, adding other components, stirring, and making into cream.

The present invention has been illustrated by the description of the preferred embodiments above, but it is to be understood that variations and modifications can be made on these embodiments by the skilled person without departing from the spirit or scope of the present invention as expressed in the following claims.

Sequence listing

<110> Winzhou Qianri Biotechnology Ltd

<120> peptide for promoting wound healing and use thereof

<130>2

<160>2

<170>PatentIn version 3.5

<210>1

<211>10

<212>PRT

<213> Artificial sequence

<220>

<223>sq1

<400>1

Ala Leu Ala Cys Pro Met Asn Thr His Ala

1 5 10

<210>2

<211>11

<212>PRT

<213> Artificial sequence

<220>

<223>sq2

<400>2

Cys Asn Ala Arg Thr Ser Met Ile Tyr Leu Thr

1 5 10

Claims (9)

1. A Peptide, referred to as "Peptide 05", consisting of SEQ ID NO: 1.

2. A combination of peptides comprising SEQ ID NO:1 and SEQ ID NO: 2.

3. A composition for promoting wound healing comprising the peptide of claim 1, or a combination comprising the peptide of claim 2.

4. Use of a peptide according to claim 1 in the preparation of a composition for promoting wound healing.

5. A cream having a wound healing promoting effect, comprising: SEQ ID NO:1 and SEQ ID NO:2, glutathione, taurine, 1, 3-propanediol, tea extract, rose hip oil, sweet almond oil, aloe extract, carbomer, asiaticoside, dextran, tremella extract, soy isoflavones, zedoary extract, dendrobium officinale extract and lauroyl arginine ethyl ester.

6. The cream according to claim 5, comprising in weight%:

0.0005-0.001% by weight of SEQ ID NO:1 peptide and/or SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

7. The cream according to claim 6, comprising in weight%:

0.001 wt% of SEQ ID NO:1 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

8. The cream according to claim 6, comprising in weight%:

0.001 wt% of SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.

9. The cream according to claim 6, comprising in weight%:

0.0005 wt% of SEQ ID NO:1 peptide and 0.0005 wt% of SEQ ID NO:2 peptide, 2.0-4.0 glutathione, 0.5-2.5 taurine, 2.0-4.0 1, 3-propylene glycol, 4.0-6.0 tea extract, 2.0-4.0 rose hip oil, 2.0-4.0 sweet almond oil, 2.0-4.0 aloe extract, 8.0-12.0 carbomer, 1.0-3.0 asiaticoside, 2.0-4.0 glucan, 1.0-3.0 tremella extract, 0.5-2.5 soybean isoflavone, 0.5-1.5 zedoary extract, 0.5-1.5 dendrobium officinale extract, 1.0-2.0 lauroyl arginine ethyl ester and the balance of water.