WO2022086047A1 - Composition for preventing and treating mucosal damage - Google Patents

Composition for preventing and treating mucosal damage Download PDF

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Publication number
WO2022086047A1
WO2022086047A1 PCT/KR2021/014211 KR2021014211W WO2022086047A1 WO 2022086047 A1 WO2022086047 A1 WO 2022086047A1 KR 2021014211 W KR2021014211 W KR 2021014211W WO 2022086047 A1 WO2022086047 A1 WO 2022086047A1
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composition
treating mucosal
mucosal wounds
mucosa
wounds
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PCT/KR2021/014211
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French (fr)
Korean (ko)
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이상철
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이상철
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present application relates to a composition for preventing and treating mucosal damage.
  • Saussurea pulchella (Fisch.) is a plant that inhabits Korea, Japan, northeastern China, Siberia, and Sakhalin. Gakshichwi is harvested in summer and autumn, and the medicinal properties are bitter, cold in nature, and non-toxic. The efficacy of gakshichi is to remove wind, clear heat, relieve anger, remove moisture, stop bleeding, and stop pain, and it is mainly used for rheumatoid arthritis and abdominal pain and diarrhea.
  • damage to mucosal tissue may occur due to disease, chemotherapy or radiation treatment, or trauma.
  • the integrity of the mucous membranes is due to vitamin deficiency, poor diet, poor hygiene, bacterial, viral or fungal infections, intestinal dysbiosis, changes in the mucosal microbial flora, endocrine imbalance, debilitating diseases, It can be influenced by several extrinsic and endogenous causes, such as genetic factors, mechanical, physical, chemical and traumatic factors, radiation, and the like.
  • the damaged skin or mucous membrane contains dying cells, microorganisms, and contaminants, Cells, microorganisms, and contaminants must be removed or decomposed, and a protease is secreted to decompose the cells, microorganisms and contaminants.
  • the excess proteolytic enzyme decomposes and destroys the intercellular collagen matrix and elastin matrix essential for cell growth and cell adhesion, thereby inhibiting cell growth. delays wound healing.
  • MMPs intercellular matrices
  • Chronic inflammatory diseases can be considered to be caused by reactive oxygen species (ROS) generated in oxidative reactions during the metabolic process of the living body.
  • ROS reactive oxygen species
  • NO reactive oxygen species
  • iNOS inducible NO synthase
  • inflammatory mediators such as NO generated by iNOS and prostaglandin E2 (PGE2) generated by cyclooxyfenase-2 (COS-2) lead back to the NO formation process in the metabolic process, and tumor necrosisfactor-a ( Inflammation-mediated cytokines such as TNF-a), interleukin-1a (IL-1a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) are called nucleartranscription factor-kappa B (NF-kB). Synthesis is regulated by transcription factors, and as it promotes ROS generation, it can exacerbate various inflammatory diseases.
  • PGE2 prostaglandin E2
  • COS-2 cyclooxyfenase-2
  • Korean Patent Publication No. 10-1845472 which is the background technology of the present application, relates to a topical composition for preserving or restoring the integrity of the mucous membrane, specifically choline alfoscerate, which is used to maintain and restore the integrity of the mucous membrane. It relates to a topical composition containing However, there is no mention of a composition for treating mucosal wounds comprising an extract of Saussurea pulchella (Fisch.) as an active ingredient.
  • the present application is to solve the problems of the prior art, and an object of the present application is to provide a composition for preventing and treating mucosal damage.
  • the first aspect of the present application provides a composition for treating mucosal wounds comprising an extract of Saussurea pulchella (Fisch.) as an active ingredient.
  • the composition for treating mucosal wounds may include Pulchellamin G as an active ingredient, but is not limited thereto.
  • the content of the extract of Saussurea pulchella (Fisch.) in the composition for treating mucosal wounds may be 0.5% (w/v) to 50% (w/v),
  • the present invention is not limited thereto.
  • the composition for treating mucosal wounds is Alchemilla vulgaris, Vitis vinifera, Camellia sinensis, Vaccinium sp., Vaccinoum myrtillus (Vaccinoum myrtillus), Mimosa tenuiflora (Mimosa tenuiflora), Echinacea purpura (Echinacea purpura) and a plant extract of those selected from the group consisting of combinations thereof may be added , but is not limited thereto.
  • the content of the vegetable extract in the composition for treating mucosal wounds may be 2% (w/v) to 5% (w/v), but is not limited thereto.
  • the composition for treating mucosal wounds may further include one selected from the group consisting of glycerin, honey, hyaluronic acid, xanthan gum, collagen, and combinations thereof, but is not limited thereto. .
  • the mucous membrane is intestinal mucosa, gastric mucosa, airway mucosa, skin mucosa, mouth and oral mucosa, nasal mucosa, eye mucosa, ear mucosa, genital mucosa and anal mucosa, rectal mucosa, and combinations thereof. It may be selected from the group consisting of, but is not limited thereto.
  • the composition for treating mucosal wounds may be for use in preventing or treating inflammatory disorders or inflammatory lesions of the mucosa, but is not limited thereto.
  • the composition for treating mucosal wounds includes enteritis (gastroenteritis), ischemic necroses, intestinal mucosal ulceration (ulceration), ulcerative colitis (UC), Crohn's disease; CD) and combinations thereof, but may be for use in the prevention or treatment of those selected from the group consisting of, but is not limited thereto.
  • the composition for treating mucosal wounds may further include one selected from the group consisting of pharmaceutically acceptable carriers, excipients, diluents, and combinations thereof, but is not limited thereto.
  • the carrier, excipient and diluent are, each independently, lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin , calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium, stearate, mineral oil and combinations thereof. It may include, but is not limited to.
  • the composition for treating mucosal wounds is selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, liniments, pastas, cataplasmases, and combinations thereof. It may be administered in the form of a selected skin external preparation, but is not limited thereto.
  • the composition for treating mucosal wounds according to the present application can inhibit proteolytic enzymes by discharging exudates from the inside of the wound. Therefore, by neutralizing the activity of the proteolytic enzyme, it is possible to inhibit the decomposition of the matrix, thereby promoting matrix repair and cell growth at the wound site.
  • composition for treating mucosal wounds according to the present application can remove the infected bacteria and other contaminants by discharging exudates from the inside of the skin to the skin wound by high osmotic pressure.
  • composition for treating mucosal wounds suppresses moisture evaporation to maintain a moist state, and increases the density to increase the blocking effect from air, thereby increasing the wound healing effect and pain relief effect.
  • composition for treating mucosal wounds according to the present application can prevent or treat inflammatory disorders or inflammatory lesions of the mucous membrane.
  • 1 is an image showing the results of measuring the mucosal skin wound treatment effect under in vivo conditions using the composition for treating mucosal wounds prepared in Examples of the present application.
  • FIG. 2 is an image showing the results of measuring the mucosal skin wound treatment effect under in vivo conditions using the composition for treating mucosal wounds prepared in Examples of the present application.
  • composition for treating mucosal wounds of the present application will be described in detail with reference to embodiments, examples, and drawings.
  • the present application is not limited to these embodiments and examples and drawings.
  • the first aspect of the present application provides a composition for treating mucosal wounds comprising an extract of Saussurea pulchella (Fisch.) as an active ingredient.
  • the wound may be selected from the group consisting of a wound, abrasion, laceration, stab wound, ulcer, and combinations thereof, but is not limited thereto.
  • the composition for treating mucosal wounds may include Pulchellamin G as an active ingredient, but is not limited thereto.
  • Chronic inflammatory diseases can be considered to be caused by reactive oxygen species (ROS) generated in oxidative reactions during the metabolic process of the living body.
  • ROS reactive oxygen species
  • NO reactive oxygen species
  • iNOS inducible NO synthase
  • inflammatory mediators such as NO generated by iNOS and prostaglandin E2 (PGE2) generated by cyclooxyfenase-2 (COS-2) lead back to the NO formation process in the metabolic process, and tumor necrosisfactor-a ( Inflammation-mediated cytokines such as TNF-a), interleukin-1a (IL-1a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) are called nucleartranscription factor-kappa B (NF-kB). Synthesis is regulated by transcription factors, and as it promotes ROS generation, it can exacerbate various inflammatory diseases.
  • PGE2 prostaglandin E2
  • COS-2 cyclooxyfenase-2
  • amino acid-sesquiterpene lactone compounds, polyphenols, and flavonoids among the components of each shichwi are known as enzymes that show a cytoprotective effect from damage caused by oxidative stress, and effectively inhibit the secretion of NO. Inhibits the anti-inflammatory effect.
  • Felchelamin G is an amino acid-sesquiterpene lactone-based compound that is isolated from each stalk.
  • Increases the expression and activity of hematin oxidase-1 (HemeOxygenase-1, HO-1), known as an enzyme that exhibits a cytoprotective effect from damage caused by oxidative stress, and secretion of NO that can directly induce inflammation can effectively inhibit the production and activation of cytokines associated with inflammation causing the secretion and inflammation of the NO.
  • composition for treating mucosal wounds according to the present application has antioxidant and anti-inflammatory activity by including Pulchellamin G as an active ingredient. Accordingly, it is possible to promote the treatment of mucosal wounds caused by inflammation.
  • the content of the extract of Saussurea pulchella (Fisch.) in the composition for treating mucosal wounds may be from about 0.5% (w/v) to about 50% (w/v).
  • the present invention is not limited thereto.
  • the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds may be about 1.5% (w/v), but is not limited thereto.
  • the composition for treating mucosal wounds is Alchemilla vulgaris, Vitis vinifera, Camellia sinensis, Vaccinium sp., Vaccinoum myrtillus (Vaccinoum myrtillus), Mimosa tenuiflora (Mimosa tenuiflora), Echinacea purpura (Echinacea purpura) and a plant extract of those selected from the group consisting of combinations thereof may be added , but is not limited thereto.
  • composition for treating mucosal wounds may further include an Alchemilla vulgaris extract, but is not limited thereto.
  • composition for treating mucosal wounds can inhibit proteolytic enzymes by discharging exudates from the inside of the wound. Therefore, by neutralizing the activity of the proteolytic enzyme, it is possible to inhibit the decomposition of the matrix, thereby promoting cell growth and treatment of the wound site.
  • the plant extract for example, Alchemilla vulgaris, the procyanidins and tannin components contained in Mimosa tenuiflora are exudates discharged to the outside of the wound tissue. It is possible to prevent the exudate containing microorganisms and contaminants from re-entering the tissue by adsorbing them.
  • polyphenols and polysaccharides which are known to precipitate large molecules contained in the plant extract, can bind to proteolytic enzymes to neutralize proteolytic enzymes.
  • polyphenols and polysaccharides have a strong affinity for proteins, and thus can promote cell growth by binding to bacterial or viral proteins and reducing the risk of infection and toxic substances of microbial origin.
  • procyanidin contained in the plant extract inhibits the activity of protease and intercellular matrix degrading enzymes in the wound to help the adhesion and growth of cells that help wound healing.
  • Healing can be promoted by forming an environment that becomes this
  • Vitis vinifera extract contains proenthocyanidins, an antioxidant, and has a strong antioxidant effect that is about 20 to about 50 times higher than that of vitamins. It can prevent aging and protect the mucous membrane.
  • the botanical extract for example, Camellia sinensis (Camellia sinensis) extract by including a catechin component, can have anti-inflammatory, detoxification, sterilization, antibacterial action.
  • Camellia sinensis (Camellia sinensis) extract by including a catechin component can have anti-inflammatory, detoxification, sterilization, antibacterial action.
  • the botanical extract for example, Vaccinoum myrtillus extract, by including an antioxidant component, can promote wound healing by strengthening arteries, veins, and capillary blood vessels.
  • the content of the vegetable extract in the composition for treating mucosal wounds may be from about 2% (w/v) to about 5% (w/v), but is not limited thereto.
  • the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds is about 1.5% (w/v), and the content of the vegetable extract is about 3.0% (w/v) may be, but is not limited thereto.
  • the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds is about 1.5% (w/v)
  • the content of the Alchemilla vulgaris extract is about 3.0% (w/v) may be, but is not limited thereto.
  • the composition for treating mucosal wounds may further include one selected from the group consisting of glycerin, honey, hyaluronic acid, xanthan gum, collagen, and combinations thereof, but is not limited thereto. .
  • composition for treating mucosal wounds may further include glycerin, honey and hyaluronic acid, but is not limited thereto.
  • the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds is about 1.5% (w/v)
  • the content of the Alchemilla vulgaris extract is about 3.0% (w/v)
  • the content of the glycerin is 63% (w/v)
  • the content of the honey is 32% (w/v)
  • the content of the hyaluronic acid is 0.5% (w/v)
  • the present invention is not limited thereto.
  • composition for treating mucosal wounds according to the present application contains glycerol, pain can be relieved with a high moisturizing effect.
  • the high concentration of glycerin can contract the cells in the body to discharge the exudate moving to the outside to the outside of the tissue.
  • glycerin has a high osmotic pressure and because it has a binding force in the form of a polymer, it does not penetrate into the tissue and exists outside the wound. Therefore, glycerin is combined with the vegetable extract to apply a film film on the wound in a state in which the viscosity is increased. Therefore, the exudate discharged to the outside of the tissue is combined with the tannin component of the vegetable extract and does not flow back into the body tissue.
  • honey supplies sufficient moisture to the mucous membrane when applied to the mucous membrane, and contains an antibacterial component, so it can promote wound healing.
  • hyaluronic acid is a high molecular compound consisting of N- acetylglucosamine and glucuronic acid.
  • Hyaluronic acid can promote wound healing by reconstructing tissues, regenerating cells, and preventing contamination of the wound and the spread of infection by preventing invasion of bacteria or poisons.
  • Collaken is also a fibrous protein found mostly in animals and humans, especially in the skin, connective tissues such as muscles and tendons.
  • platelets aggregate to the collagen and maintain coagulation factors that are peeled off together with the plasma, thereby finally forming a blood clot with fibrin to have a hemostatic effect.
  • Xanthan Gum (Xanthan Gum) is a powder mixture obtained by refining, drying, and pulverizing a high molecular weight polysaccharide gum in isopropyl alcohol, and is dissolved in water to increase the adhesion and viscosity of the composition for treating mucosal wounds according to the present invention. It can be used as a thickener.
  • the composition for treating mucosal wounds has antioxidant and anti-inflammatory effects by including Saussurea pulchella (Fisch.) extract as an active ingredient, Discharges exudate to skin wounds to sterilize infected bacteria and other contaminants, prevents infection of wounds by preventing bacterial penetration with the hyaluronic acid, and neutralizes proteolytic enzymes that destroy intercellular matrix with herbal extracts It restores the matrix and binds to bacterial or viral proteins to reduce the release of infection and toxic substances, promotes cell growth, promotes wound healing, and maintains moisture by inhibiting water evaporation with the glycerin, When applied to the skin, it supplies sufficient moisture to the wounded area and promotes wound healing by antibacterial ingredients.
  • Saussurea pulchella (Fisch.) extract Discharges exudate to skin wounds to sterilize infected bacteria and other contaminants, prevents infection of wounds by preventing bacterial penetration with the hyaluronic acid, and neutralizes proteolytic enzymes that destroy intercellular matrix with herbal extract
  • the mucous membrane is intestinal mucosa, gastric mucosa, airway mucosa, skin mucosa, mouth and oral mucosa, nasal mucosa, eye mucosa, ear mucosa, genital mucosa and anal mucosa, rectal mucosa, and combinations thereof. It may be selected from the group consisting of, but is not limited thereto.
  • the composition for treating mucosal wounds may be for use in preventing or treating inflammatory disorders or inflammatory lesions of the mucosa, but is not limited thereto.
  • the composition for treating mucosal wounds according to the present application contains pulselamine G (Pulchellamin G) as an active ingredient, so that hematin oxidase-1 known as an enzyme exhibiting a cytoprotective effect from damage caused by oxidative stress Increases the expression and activity of (HemeOxygenase-1, HO-1), can effectively inhibit the secretion of NO, which can directly induce inflammation, and the secretion of NO and inflammation-related cytokines production and activation can be effectively inhibited.
  • Pulchellamin G Pulchellamin G
  • the composition for treating mucosal wounds includes enteritis (gastroenteritis), ischemic necroses, intestinal mucosal ulceration (ulceration), ulcerative colitis (UC), Crohn's disease; CD) and combinations thereof, but may be for use in the prevention or treatment of those selected from the group consisting of, but is not limited thereto.
  • the most common and major symptom in inflammatory bowel diseases such as enteritis, ischemic necrosis, intestinal mucosal ulceration, ulcerative colitis, and Crohn's disease is damage to the mucous membrane. Damage to the mucous membrane is caused by inflammation.
  • composition for treating mucosal wounds has antioxidant and anti-inflammatory activity by including Pulchellamin G as an active ingredient. Accordingly, by promoting the treatment of mucosal wounds caused by inflammation, it is possible to promote the treatment of the inflammatory bowel disease.
  • Colitis is a disease that causes inflammation of the large intestine, and it occurs due to various causes. In some cases. Colitis may be largely divided into infectious colitis and non-infectious colitis according to the cause, and may be divided into acute colitis and chronic colitis according to the onset period. Acute colitis includes amoebic dysentery, bacterial dysentery, and pseudomembranous enteritis caused by salmonella or antibiotics, and chronic colitis includes ulcerative colitis, Crohn's disease, tuberculosis, syphilis, and X-rays. In addition, colitis includes irritable bowel syndrome (IBS) as well as inflammatory bowel disease (IBD).
  • IBS irritable bowel syndrome
  • IBD inflammatory bowel disease
  • IBD inflammatory bowel disease
  • Ulcerative colitis is a disease in which erosions or ulcers are continuously formed on the mucous membrane of the large intestine. systemic symptoms of In addition, ulcerative colitis can occur anywhere in the gastrointestinal tract.
  • Crohn's disease is a disease in which lesions such as ulcers occur discontinuously in any part of the digestive tract from the mouth to the anus. Symptoms such as general malaise and anemia appear.
  • the composition for treating mucosal wounds may further include one selected from the group consisting of pharmaceutically acceptable carriers, excipients, diluents, and combinations thereof, but is not limited thereto.
  • the carrier, excipient and diluent are, each independently, lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin , calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium, stearate, mineral oil and combinations thereof. It may include, but is not limited to.
  • the composition for treating mucosal wounds is selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, liniments, pastas, cataplasmases, and combinations thereof. It may be administered in the form of a selected skin external preparation, but is not limited thereto.
  • the extracts from each sagittal route are subcutaneous route, intramuscular route, intravenous route, intrathecal route, sublingual route, buccal route, rectal route, vaginal route, ocular route, ear route, nasal route, inhalation route, nebulization route, dermal route , may be administered by a route selected from the group consisting of transdermal routes and combinations thereof, but is not limited thereto.
  • the dosage may be appropriately determined by a person skilled in the art based on conditions such as, but not limited to, the properties of the substance, toxicity, the type of administration target, age, weight, and health.
  • the concentrate was filtered twice with a PES filter to improve stability.
  • Alchemyra vulgaris leaf extract 3.0% (w/v), glycerin 63.0 wt%, honey 32% (w/v) and hyaluronic acid 0.5% ( w/v) was mixed, and stirred after lowering the internal air pressure.
  • 1 and 2 are images showing the results of measuring the mucosal skin wound treatment effect in vivo conditions using the composition for treating mucosal wounds prepared in Example 2 of the present application.
  • a virtual lesion (2 cm in diameter round) was marked in a mini-pig (Sus scrofa) model, and endoscopic submucosal dissection was performed.
  • Example 2 the composition for treating mucosal wounds prepared in Example 2 was applied to the experimental group for 14 days for artificial ulcers that occurred after the procedure, and nothing was applied to the control group.
  • the esophagus, stomach, and large intestine were extracted, fixed in 10% neutral buffered formalin solution, observed with the naked eye (FIG. 1), cut to a certain thickness, and then paraffin-embedded through a general tissue treatment process to form a 4 ⁇ m tissue Sections were prepared. Then, H&E staining was performed and histopathological findings were observed using an optical microscope (FIG. 2).
  • composition for treating mucosal wounds according to the present application when applied, it was confirmed that the damage due to inflammation was less than that of the control group. Therefore, it was confirmed that the composition for treating mucosal wounds prepared in Example 2 of the present application exhibited a significant mucosal wound healing effect on the esophageal mucosa, gastric mucosa, and colonic mucosa compared to the control group.

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Abstract

The present application relates to a composition for treating mucosal wounds, comprising a Saussurea pulchella (Fisch.) extract as an active ingredient.

Description

점막 손상의 예방 및 치료용 조성물Composition for preventing and treating mucosal damage
본원은 점막 손상의 예방 및 치료용 조성물에 관한 것이다.The present application relates to a composition for preventing and treating mucosal damage.
각시취(Saussurea pulchella (Fisch.))는 한국, 일본, 중국 북동부, 동시베리아, 사할린 등지에 서식하는 식물이다. 각시취는 여름과 가을철에 전초를 채취하며, 약성은 맛이 매우면서 쓰고, 성질이 차며, 독이 없다. 각시취의 효능은 풍을 제거하고, 열을 맑히고 화를 내려주며, 습기를 없애주고, 출혈을 멎게 하며, 아픈 것을 그치게 하며, 주로 풍습성관절염 및 복통설사에 사용되고 있다.Saussurea pulchella (Fisch.) is a plant that inhabits Korea, Japan, northeastern China, Siberia, and Sakhalin. Gakshichwi is harvested in summer and autumn, and the medicinal properties are bitter, cold in nature, and non-toxic. The efficacy of gakshichi is to remove wind, clear heat, relieve anger, remove moisture, stop bleeding, and stop pain, and it is mainly used for rheumatoid arthritis and abdominal pain and diarrhea.
한편, 점막 조직의 손상은 질병, 화학요법 또는 방사선 치료 또는 외상으로 인해 발생할 수 있다. 점막의 완전성은 비타민 결핍, 잘못된 식이, 불량한 위생, 박테리아, 바이러스 또는 진균 감염, 장내 세균총 불균형(intestinal dysbiosis), 점막 미생물 균상(mucosal microbial flora)의 변화, 내분비 불균형, 쇠약성 질환(debilitating disease), 유전 인자, 기계적, 물리적, 화학적 및 외상성 인자, 방사선 등과 같은, 여러 외인성 및 내인성 원인에 의해 영향을 받을 수 있다.On the other hand, damage to mucosal tissue may occur due to disease, chemotherapy or radiation treatment, or trauma. The integrity of the mucous membranes is due to vitamin deficiency, poor diet, poor hygiene, bacterial, viral or fungal infections, intestinal dysbiosis, changes in the mucosal microbial flora, endocrine imbalance, debilitating diseases, It can be influenced by several extrinsic and endogenous causes, such as genetic factors, mechanical, physical, chemical and traumatic factors, radiation, and the like.
이와 관련하여, 신체의 주요 부분을 덮고 있는 피부나 점막의 손상과 함께 내부조직까지 손상된 경우, 상기 손상된 피부나 점막에는 죽어가는 세포, 미생물, 오염물질이 포함되어 있어, 상기 피부나 점막에 포함된 세포, 미생물, 오염물질을 제거하거나 분해하여야 하는데, 여기서 상기 세포, 미생물, 오염물질들을 분해하기 위해 단백질 분해 효소(protease)를 분비하게 된다.In this regard, when internal tissues are damaged along with damage to the skin or mucous membrane covering a major part of the body, the damaged skin or mucous membrane contains dying cells, microorganisms, and contaminants, Cells, microorganisms, and contaminants must be removed or decomposed, and a protease is secreted to decompose the cells, microorganisms and contaminants.
그러나 상기 분비되는 단백질 분해 효소가 과잉 분비되는 경우, 과잉 단백질 분해 효소는 세포의 성장 및 세포 부착에 필수적인 세포 간 콜라겐(Collagen) 매트릭스와 엘라스틴(Elastin) 매트릭스를 분해 및 파괴시켜 세포의 성장을 억제하여 상처 치유를 지연시키게 된다.However, when the secreted proteolytic enzyme is excessively secreted, the excess proteolytic enzyme decomposes and destroys the intercellular collagen matrix and elastin matrix essential for cell growth and cell adhesion, thereby inhibiting cell growth. delays wound healing.
상기 단백질 분해 효소(protease)를 억제하면, 세포와 세포 사이에 공간을 채워 주는 단백질인 콜라겐, 엘라스틴, 히알루론산 등의 세포 간 매트릭스(MMPs:matrix metalloproteins)의 분해가 억제되어 세포의 성장을 촉진시키게 된다.When the protease is inhibited, the decomposition of intercellular matrices (MMPs) such as collagen, elastin, and hyaluronic acid, which are proteins that fill the space between cells, is inhibited to promote cell growth. do.
한편, 점막 조직의 손상은 염증으로 인해 발생할 수 있다. 만성 염증성 질환 등은 생체의 대사 과정 중 산화 반응에서 발생한 활성산소류(reactive oxygen species, ROS)에 의한다고 볼 수 있으며, 활성산소는 생체 내의 물질과 반응하여 산화적 스트레스를 유발하고 이러한 산화적 스트레스는 인체 내 다양한 조직 세포를 손상시켜 아토피성 피부염 등 여러 만성 염증성 질환을 유발시킨다.On the other hand, damage to the mucosal tissue may occur due to inflammation. Chronic inflammatory diseases can be considered to be caused by reactive oxygen species (ROS) generated in oxidative reactions during the metabolic process of the living body. Causes various chronic inflammatory diseases such as atopic dermatitis by damaging various tissue cells in the human body.
활성산소의 하나인 nitric oxide(NO) 는 염증 반응 시 inducible NO synthase(iNOS) 에 의해 과생성되어 부종, 발열, 조직손상 등의 염증반응을 촉발한다.One of the reactive oxygen species, nitric oxide (NO), is overproduced by inducible NO synthase (iNOS) during an inflammatory reaction, triggering inflammatory reactions such as edema, fever, and tissue damage.
이러한 염증 과정 중에 iNOS 에 의해 발생되는 NO 와 cyclooxyfenase-2(COS-2) 에 의해 생성되는 prostaglandin E2(PGE2) 등의 염증매개물질들은 대사 과정에서 NO 형성 과정으로 다시 이어지게되고, tumor necrosisfactor-a(TNF-a), interleukin-1a(IL-1a), interleukin-1b(IL-1b), interleukin-6(IL-6) 등의 염증매개 사이토카인 등은 nucleartranscription factor-kappa B(NF-kB) 라는 전사인자에 의해 합성이 조절되며, ROS 의 생성을 촉진시킴에 따라 여러 염증성 질환들을 악화시킬 수 있다.During this inflammatory process, inflammatory mediators such as NO generated by iNOS and prostaglandin E2 (PGE2) generated by cyclooxyfenase-2 (COS-2) lead back to the NO formation process in the metabolic process, and tumor necrosisfactor-a ( Inflammation-mediated cytokines such as TNF-a), interleukin-1a (IL-1a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) are called nucleartranscription factor-kappa B (NF-kB). Synthesis is regulated by transcription factors, and as it promotes ROS generation, it can exacerbate various inflammatory diseases.
본원의 배경이 되는 기술인 대한한국 등록특허공보 제 10-1845472 호는 점막의 완전성을 보존하거나 회복시키기 위한 국소용 조성물에 관한 것으로, 구체적으로 점막의 완전성을 유지 및 회복시키는데 사용되는, 콜린 알포세레이트를 함유하는 국소용 조성물에에 관한 것이다. 그러나, 각시취(Saussurea pulchella (Fisch.)) 추출물을 유효성분으로 포함하는 점막 상처 치료용 조성물 에 대해서는 언급하지 않고 있다.Korean Patent Publication No. 10-1845472, which is the background technology of the present application, relates to a topical composition for preserving or restoring the integrity of the mucous membrane, specifically choline alfoscerate, which is used to maintain and restore the integrity of the mucous membrane. It relates to a topical composition containing However, there is no mention of a composition for treating mucosal wounds comprising an extract of Saussurea pulchella (Fisch.) as an active ingredient.
본원은 전술한 종래 기술의 문제점을 해결하기 위한 것으로서, 점막 손상의 예방 및 치료용 조성물을 제공하는 것을 목적으로 한다.The present application is to solve the problems of the prior art, and an object of the present application is to provide a composition for preventing and treating mucosal damage.
다만, 본원의 실시예가 이루고자 하는 기술적 과제는 상기된 바와 같은 기술적 과제들로 한정되지 않으며, 또 다른 기술적 과제들이 존재할 수 있다.However, the technical problems to be achieved by the embodiments of the present application are not limited to the technical problems described above, and other technical problems may exist.
상기한 기술적 과제를 달성하기 위한 기술적 수단으로서, 본원의 제 1 측면은, 각시취(Saussurea pulchella (Fisch.)) 추출물을 유효성분으로 포함하는 점막 상처 치료용 조성물을 제공한다.As a technical means for achieving the above technical problem, the first aspect of the present application provides a composition for treating mucosal wounds comprising an extract of Saussurea pulchella (Fisch.) as an active ingredient.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 펄첼라민 G(Pulchellamin G) 를 유효성분으로 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may include Pulchellamin G as an active ingredient, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은 0.5%(w/v) 내지 50%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the content of the extract of Saussurea pulchella (Fisch.) in the composition for treating mucosal wounds may be 0.5% (w/v) to 50% (w/v), However, the present invention is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 알케미라 불가리스(Alchemilla vulgaris), 비티스 비니페라(Vitis vinifera), 카멜리아 시넨시스(Camellia sinensis), 바시니움 에스피(Vaccinium sp.), 바시니움 미르티루스(Vaccinoum myrtillus), 미모사 테누이플로라(Mimosa tenuiflora), 에키나세아 프르푸라(Echinacea purpura) 및 이들의 조합들로 이루어진 군으로부터 선택되는 것의 식물성추출물을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds is Alchemilla vulgaris, Vitis vinifera, Camellia sinensis, Vaccinium sp., Vaccinoum myrtillus (Vaccinoum myrtillus), Mimosa tenuiflora (Mimosa tenuiflora), Echinacea purpura (Echinacea purpura) and a plant extract of those selected from the group consisting of combinations thereof may be added , but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물 중 상기 식물성추출물의 함량은 2%(w/v) 내지 5%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the content of the vegetable extract in the composition for treating mucosal wounds may be 2% (w/v) to 5% (w/v), but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 글리세린, 꿀, 히알루론산, 잔탄검, 콜라겐 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may further include one selected from the group consisting of glycerin, honey, hyaluronic acid, xanthan gum, collagen, and combinations thereof, but is not limited thereto. .
본원의 일 구현예에 따르면, 상기 점막은 장 점막, 위 점막, 기도 점막, 피부 점막, 입과 구강의 점막, 비점막, 안구 점막, 귀 점막, 생식기 점막 및 항문 점막, 직장 점막 및 이들의 조합들로 이루어진 군으로부터 선택되는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the mucous membrane is intestinal mucosa, gastric mucosa, airway mucosa, skin mucosa, mouth and oral mucosa, nasal mucosa, eye mucosa, ear mucosa, genital mucosa and anal mucosa, rectal mucosa, and combinations thereof. It may be selected from the group consisting of, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 점막의 염증 장애 또는 염증 병소를 예방 또는 치료하는데 사용하기 위한 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may be for use in preventing or treating inflammatory disorders or inflammatory lesions of the mucosa, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 장염(gastroenteritis), 허혈성 괴사(ischemic necroses), 장 점막 궤양(ulceration), 궤양성 대장염(ulcerative colitis; UC), 크론병(Crohn's disease; CD) 및 이들의 조합들로 이루어진 군으로부터 선택되는 것의 예방 또는 치료에 사용하기 위한 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds includes enteritis (gastroenteritis), ischemic necroses, intestinal mucosal ulceration (ulceration), ulcerative colitis (UC), Crohn's disease; CD) and combinations thereof, but may be for use in the prevention or treatment of those selected from the group consisting of, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 약학적으로 허용가능한 담체, 부형제, 희석제 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may further include one selected from the group consisting of pharmaceutically acceptable carriers, excipients, diluents, and combinations thereof, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 담체, 부형제 및 희석제는, 각각 독립적으로, 락토즈, 덱스트로즈, 수크로즈, 올리고당, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘, 스테아레이트, 광물유 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the carrier, excipient and diluent are, each independently, lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin , calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium, stearate, mineral oil and combinations thereof. It may include, but is not limited to.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 크림, 겔, 패치, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제, 카타플라스마제 및 이들의 조합들로 이루어진 군으로부터 선택되는 피부 외용제 형태로 투여되는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds is selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, liniments, pastas, cataplasmases, and combinations thereof. It may be administered in the form of a selected skin external preparation, but is not limited thereto.
상술한 과제 해결 수단은 단지 예시적인 것으로서, 본원을 제한하려는 의도로 해석되지 않아야 한다. 상술한 예시적인 실시예 외에도, 도면 및 발명의 상세한 설명에 추가적인 실시예가 존재할 수 있다.The above-described problem solving means are merely exemplary, and should not be construed as limiting the present application. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and detailed description.
전술한 본원의 과제 해결 수단에 의하면, 본원에 따른 점막 상처 치료용 조성물은 상처 내부로부터 삼출물을 배출하여 단백질 분해 효소를 억제할 수 있다. 따라서, 상기 단백질 분해 효소의 활성을 중화함으로써 매트릭스의 분해를 억제시켜서 상처부위의 매트릭스 복구, 세포 성장을 촉진할 수 있다.According to the above-described means for solving the problems of the present application, the composition for treating mucosal wounds according to the present application can inhibit proteolytic enzymes by discharging exudates from the inside of the wound. Therefore, by neutralizing the activity of the proteolytic enzyme, it is possible to inhibit the decomposition of the matrix, thereby promoting matrix repair and cell growth at the wound site.
또한 본원에 따른 점막 상처 치료용 조성물은 높은 삼투압에 의해 피부 내부로부터 피부 상처에 삼출물을 배출시켜서 감염된 세균 및 기타 오염물질을 제거할 수 있다. In addition, the composition for treating mucosal wounds according to the present application can remove the infected bacteria and other contaminants by discharging exudates from the inside of the skin to the skin wound by high osmotic pressure.
또한 본원에 따른 점막 상처 치료용 조성물은 수분증발을 억제하여 보습 상태를 유지하며, 밀도를 높여서 공기와의 차단효과를 증대시킴으로써 상처 치료 효과 및 통증 완화 효과를 증대 시킬 수 있다.In addition, the composition for treating mucosal wounds according to the present application suppresses moisture evaporation to maintain a moist state, and increases the density to increase the blocking effect from air, thereby increasing the wound healing effect and pain relief effect.
또한 본원에 따른 점막 상처 치료용 조성물은 점막의 염증 장애 또는 염증 병소를 예방 또는 치료할 수 있다.In addition, the composition for treating mucosal wounds according to the present application can prevent or treat inflammatory disorders or inflammatory lesions of the mucous membrane.
다만, 본원에서 얻을 수 있는 효과는 상기된 바와 같은 효과들로 한정되지 않으며, 또 다른 효과들이 존재할 수 있다.However, the effects obtainable herein are not limited to the above-described effects, and other effects may exist.
도 1 은 본원의 실시예에서 제조한 점막 상처 치료용 조성물을 이용한 in vivo 조건에서의 점막 피부 상처 치료 효과를 측정한 결과를 나타낸 이미지이다.1 is an image showing the results of measuring the mucosal skin wound treatment effect under in vivo conditions using the composition for treating mucosal wounds prepared in Examples of the present application.
도 2 는 본원의 실시예에서 제조한 점막 상처 치료용 조성물을 이용한 in vivo 조건에서의 점막 피부 상처 치료 효과를 측정한 결과를 나타낸 이미지이다.2 is an image showing the results of measuring the mucosal skin wound treatment effect under in vivo conditions using the composition for treating mucosal wounds prepared in Examples of the present application.
아래에서는 첨부한 도면을 참조하여 본원이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본원의 실시예를 상세히 설명한다. 그러나 본원은 여러 가지 상이한 형태로 구현될 수 있으며 여기에서 설명하는 실시예에 한정되지 않는다. 그리고 도면에서 본원을 명확하게 설명하기 위해서 설명과 관계없는 부분은 생략하였으며, 명세서 전체를 통하여 유사한 부분에 대해서는 유사한 도면 부호를 붙였다.Hereinafter, embodiments of the present application will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art to which the present application pertains can easily carry out. However, the present application may be implemented in several different forms and is not limited to the embodiments described herein. And in order to clearly explain the present application in the drawings, parts irrelevant to the description are omitted, and similar reference numerals are attached to similar parts throughout the specification.
본원 명세서 전체에서, 어떤 부분이 다른 부분과 "연결"되어 있다고 할 때, 이는 "직접적으로 연결"되어 있는 경우뿐 아니라, 그 중간에 다른 소자를 사이에 두고 "전기적으로 연결"되어 있는 경우도 포함한다. Throughout this specification, when a part is "connected" with another part, this includes not only the case where it is "directly connected" but also the case where it is "electrically connected" with another element interposed therebetween. do.
본원 명세서 전체에서, 어떤 부재가 다른 부재 "상에", "상부에", "상단에", "하에", "하부에", "하단에" 위치하고 있다고 할 때, 이는 어떤 부재가 다른 부재에 접해 있는 경우뿐 아니라 두 부재 사이에 또 다른 부재가 존재하는 경우도 포함한다.Throughout this specification, when a member is positioned “on”, “on”, “on”, “on”, “under”, “under”, or “under” another member, this means that a member is positioned on the other member. It includes not only the case where they are in contact, but also the case where another member exists between two members.
본원 명세서 전체에서, 어떤 부분이 어떤 구성요소를 "포함" 한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.Throughout this specification, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.
본 명세서에서 사용되는 정도의 용어 "약", "실질적으로" 등은 언급된 의미에 고유한 제조 및 물질 허용오차가 제시될 때 그 수치에서 또는 그 수치에 근접한 의미로 사용되고, 본원의 이해를 돕기 위해 정확하거나 절대적인 수치가 언급된 개시 내용을 비양심적인 침해자가 부당하게 이용하는 것을 방지하기 위해 사용된다. 또한, 본원 명세서 전체에서, "~ 하는 단계" 또는 "~의 단계"는 "~를 위한 단계"를 의미하지 않는다.As used herein, the terms "about," "substantially," and the like are used in a sense at or close to the numerical value when the manufacturing and material tolerances inherent in the stated meaning are presented, and to aid in the understanding of the present application. It is used to prevent an unconscionable infringer from using the mentioned disclosure in an unreasonable way. Also, throughout this specification, "step to" or "step to" does not mean "step for".
본원 명세서 전체에서, 마쿠시 형식의 표현에 포함된 "이들의 조합"의 용어는 마쿠시 형식의 표현에 기재된 구성 요소들로 이루어진 군에서 선택되는 하나 이상의 혼합 또는 조합을 의미하는 것으로서, 상기 구성 요소들로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 의미한다.Throughout this specification, the term "combination of these" included in the expression of the Markush form means one or more mixtures or combinations selected from the group consisting of the components described in the expression of the Markush form, and the components It is meant to include one or more selected from the group consisting of.
본원 명세서 전체에서, "A 및/또는 B" 의 기재는, "A, B, 또는, A 및 B" 를 의미한다.Throughout this specification, reference to “A and/or B” means “A, B, or A and B”.
이하에서는 본원의 점막 상처 치료용 조성물에 대하여 구현예 및 실시예와 도면을 참조하여 구체적으로 설명하도록 한다. 그러나 본원이 이러한 구현예 및 실시예와 도면에 제한되는 것은 아니다.Hereinafter, the composition for treating mucosal wounds of the present application will be described in detail with reference to embodiments, examples, and drawings. However, the present application is not limited to these embodiments and examples and drawings.
상기한 기술적 과제를 달성하기 위한 기술적 수단으로서, 본원의 제 1 측면은, 각시취(Saussurea pulchella (Fisch.)) 추출물을 유효성분으로 포함하는 점막 상처 치료용 조성물을 제공한다.As a technical means for achieving the above technical problem, the first aspect of the present application provides a composition for treating mucosal wounds comprising an extract of Saussurea pulchella (Fisch.) as an active ingredient.
상기 상처는 창상(wound), 찰과상(abrasion), 열상(laceration), 자상(stab wound), 궤양 및 이들의 조합들로 이루어진 군으로부터 선택되는 것일 수 있으나, 이에 제한되는 것은 아니다.The wound may be selected from the group consisting of a wound, abrasion, laceration, stab wound, ulcer, and combinations thereof, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 펄첼라민 G(Pulchellamin G) 를 유효성분으로 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may include Pulchellamin G as an active ingredient, but is not limited thereto.
점막 조직의 손상은 염증으로 인해 발생할 수 있다. 만성 염증성 질환 등은 생체의 대사 과정 중 산화 반응에서 발생한 활성산소류(reactive oxygen species, ROS)에 의한다고 볼 수 있으며, 활성산소는 생체 내의 물질과 반응하여 산화적 스트레스를 유발하고 이러한 산화적 스트레스는 인체 내 다양한 조직 세포를 손상시켜 아토피성 피부염 등 여러 만성 염증성 질환을 유발시킨다.Damage to mucosal tissue can result from inflammation. Chronic inflammatory diseases can be considered to be caused by reactive oxygen species (ROS) generated in oxidative reactions during the metabolic process of the living body. Causes various chronic inflammatory diseases such as atopic dermatitis by damaging various tissue cells in the human body.
활성산소의 하나인 nitric oxide(NO) 는 염증 반응 시 inducible NO synthase(iNOS) 에 의해 과생성되어 부종, 발열, 조직손상 등의 염증반응을 촉발한다.One of the reactive oxygen species, nitric oxide (NO), is overproduced by inducible NO synthase (iNOS) during an inflammatory reaction, triggering inflammatory reactions such as edema, fever, and tissue damage.
이러한 염증 과정 중에 iNOS 에 의해 발생되는 NO 와 cyclooxyfenase-2(COS-2) 에 의해 생성되는 prostaglandin E2(PGE2) 등의 염증매개물질들은 대사 과정에서 NO 형성 과정으로 다시 이어지게되고, tumor necrosisfactor-a(TNF-a), interleukin-1a(IL-1a), interleukin-1b(IL-1b), interleukin-6(IL-6) 등의 염증매개 사이토카인 등은 nucleartranscription factor-kappa B(NF-kB) 라는 전사인자에 의해 합성이 조절되며, ROS 의 생성을 촉진시킴에 따라 여러 염증성 질환들을 악화시킬 수 있다.During this inflammatory process, inflammatory mediators such as NO generated by iNOS and prostaglandin E2 (PGE2) generated by cyclooxyfenase-2 (COS-2) lead back to the NO formation process in the metabolic process, and tumor necrosisfactor-a ( Inflammation-mediated cytokines such as TNF-a), interleukin-1a (IL-1a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) are called nucleartranscription factor-kappa B (NF-kB). Synthesis is regulated by transcription factors, and as it promotes ROS generation, it can exacerbate various inflammatory diseases.
한편, 각시취의 성분 중 아미노산-세스퀘테르펜 락톤(amino acid-sesquiterpene lactone)계 화합물, 폴리페놀 및 플라보노이드는 산화적 스트레스로 인한 손상으로부터 세포보호효과를 나타내는 효소로 알려져 있으며, NO 의 분비를 효과적으로 억제하여, 항염증 효과를 나타낸다.On the other hand, amino acid-sesquiterpene lactone compounds, polyphenols, and flavonoids among the components of each shichwi are known as enzymes that show a cytoprotective effect from damage caused by oxidative stress, and effectively inhibit the secretion of NO. Inhibits the anti-inflammatory effect.
펠첼라민 G 의 경우, 각시취로부터 분리되는 아미노산-세스퀘테르펜 락톤(amino acid-sesquiterpene lactone)계 화합물이다. 산화적 스트레스로 인한 손상으로부터의 세포보호효과를 나타내는 효소로 알려진 헤마틴 산화효소-1(HemeOxygenase-1, HO-1)의 발현 및 활성을 증가시키며, 염증을 직접적으로 유도할 수 있는 NO 의 분비를 효과적으로 억제할 수 있고, 상기 NO 의 분비 및 염증을 유발하는 염증과 관련된 사이토카인의 생성 및 활성화를 효과적으로 억제할 수 있다.In the case of Felchelamin G, it is an amino acid-sesquiterpene lactone-based compound that is isolated from each stalk. Increases the expression and activity of hematin oxidase-1 (HemeOxygenase-1, HO-1), known as an enzyme that exhibits a cytoprotective effect from damage caused by oxidative stress, and secretion of NO that can directly induce inflammation can effectively inhibit the production and activation of cytokines associated with inflammation causing the secretion and inflammation of the NO.
본원에 따른 점막 상처 치료용 조성물은 펄첼라민 G(Pulchellamin G) 를 유효성분으로 포함함으로써 항산화 및 항염증 활성을 가진다. 이에, 염증으로 인해 발생한 점막 상처의 치료를 촉진할 수 있다.The composition for treating mucosal wounds according to the present application has antioxidant and anti-inflammatory activity by including Pulchellamin G as an active ingredient. Accordingly, it is possible to promote the treatment of mucosal wounds caused by inflammation.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은 약 0.5%(w/v) 내지 약 50%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the content of the extract of Saussurea pulchella (Fisch.) in the composition for treating mucosal wounds may be from about 0.5% (w/v) to about 50% (w/v). However, the present invention is not limited thereto.
예를 들어, 상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은 약 1.5%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.For example, the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds may be about 1.5% (w/v), but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 알케미라 불가리스(Alchemilla vulgaris), 비티스 비니페라(Vitis vinifera), 카멜리아 시넨시스(Camellia sinensis), 바시니움 에스피(Vaccinium sp.), 바시니움 미르티루스(Vaccinoum myrtillus), 미모사 테누이플로라(Mimosa tenuiflora), 에키나세아 프르푸라(Echinacea purpura) 및 이들의 조합들로 이루어진 군으로부터 선택되는 것의 식물성추출물을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds is Alchemilla vulgaris, Vitis vinifera, Camellia sinensis, Vaccinium sp., Vaccinoum myrtillus (Vaccinoum myrtillus), Mimosa tenuiflora (Mimosa tenuiflora), Echinacea purpura (Echinacea purpura) and a plant extract of those selected from the group consisting of combinations thereof may be added , but is not limited thereto.
예를 들어, 상기 점막 상처 치료용 조성물은 알케미라 불가리스(Alchemilla vulgaris) 추출물을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.For example, the composition for treating mucosal wounds may further include an Alchemilla vulgaris extract, but is not limited thereto.
본원에 따른 점막 상처 치료용 조성물은 상처 내부로부터 삼출물을 배출하여 단백질 분해 효소를 억제할 수 있다. 따라서, 상기 단백질 분해 효소의 활성을 중화함으로써 매트릭스의 분해를 억제시켜서 상처부위의 세포 성장 및 치료를 촉진할 수 있다.The composition for treating mucosal wounds according to the present application can inhibit proteolytic enzymes by discharging exudates from the inside of the wound. Therefore, by neutralizing the activity of the proteolytic enzyme, it is possible to inhibit the decomposition of the matrix, thereby promoting cell growth and treatment of the wound site.
구체적으로, 상기 식물성추출물, 예를 들어, 알케미라 불가리스(Alchemilla vulgaris), 미모사 테누이플로라(Mimosa tenuiflora)에 포함된 상기 프로시아니딘(Procyanidins) 및 탄닌(tannin) 성분은 상처 조직의 외부로 배출되는 삼출물을 흡착하여 미생물 및 오염물질을 포함하는 상기 삼출물이 다시 조직 속으로 유입되는 것을 방지할 수 있다.Specifically, the plant extract, for example, Alchemilla vulgaris, the procyanidins and tannin components contained in Mimosa tenuiflora are exudates discharged to the outside of the wound tissue. It is possible to prevent the exudate containing microorganisms and contaminants from re-entering the tissue by adsorbing them.
또한, 상기 식물성추출물에 포함된 큰 분자를 침전하는 것으로 알려진 폴리페놀(Polyphenol) 및 다당류(Polysaccharide)는 단백질 분해 효소에 결합하여 단백질 분해 효소를 중화시킬 수 있다.In addition, polyphenols and polysaccharides, which are known to precipitate large molecules contained in the plant extract, can bind to proteolytic enzymes to neutralize proteolytic enzymes.
또한, 상기 폴리페놀 및 다당류는 단백질에 대한 강한 친화성을 가짐으로써, 박테리아 또는 바이러스성 단백질에 결합하여 감염 위험 및 미생물 기원의 독성 물질을 감소시켜 세포성장을 촉진할 수 있다.In addition, the polyphenols and polysaccharides have a strong affinity for proteins, and thus can promote cell growth by binding to bacterial or viral proteins and reducing the risk of infection and toxic substances of microbial origin.
또한, 상기 식물성추출물에 포함된 프로시아니딘은 상처에서 프로테아제(protease) 및 세포 간 매트릭스(MMPs)를 분해하는 효소들(intercellular matrix degrading enzymes)의 활성을 억제함으로써 상처 치유를 돕는 세포의 부착과 성장에 도움이 되는 환경을 형성하여 치유를 촉진시킬 수 있다.In addition, procyanidin contained in the plant extract inhibits the activity of protease and intercellular matrix degrading enzymes in the wound to help the adhesion and growth of cells that help wound healing. Healing can be promoted by forming an environment that becomes this
또한, 상기 식물성추출물, 예를 들어, 비티스 비니페라(Vitis vinifera) 추출물은 항산화제인 프로엔토사이아니딘스를 포함함으로써, 비타민과 비교하여 약 20 배 내지 약 50 배 높은 강력한 항산화 효과로 점막의 노화를 방지하고, 점막을 보호할 수 있다.In addition, the botanical extract, for example, Vitis vinifera extract contains proenthocyanidins, an antioxidant, and has a strong antioxidant effect that is about 20 to about 50 times higher than that of vitamins. It can prevent aging and protect the mucous membrane.
또한, 상기 식물성추출물, 예를 들어, 카멜리아 시넨시스(Camellia sinensis) 추출물은 카테킨 성분을 포함함으로써, 소염, 해독, 살균, 항균작용을 할 수 있다.In addition, the botanical extract, for example, Camellia sinensis (Camellia sinensis) extract by including a catechin component, can have anti-inflammatory, detoxification, sterilization, antibacterial action.
또한, 상기 식물성추출물, 예를 들어, 바시니움 미르티루스(Vaccinoum myrtillus) 추출물은 항산화 성분을 포함함으로써, 동맥, 정맥, 모세관 혈관을 강화하여 상처 치료를 촉진할 수 있다.In addition, the botanical extract, for example, Vaccinoum myrtillus extract, by including an antioxidant component, can promote wound healing by strengthening arteries, veins, and capillary blood vessels.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물 중 상기 식물성추출물의 함량은 약 2%(w/v) 내지 약 5%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the content of the vegetable extract in the composition for treating mucosal wounds may be from about 2% (w/v) to about 5% (w/v), but is not limited thereto.
예를 들어, 상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은 약 1.5%(w/v) 이고, 상기 식물성추출물의 함량은 약 3.0%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.For example, the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds is about 1.5% (w/v), and the content of the vegetable extract is about 3.0% (w/v) may be, but is not limited thereto.
구체적으로, 상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은 약 1.5%(w/v) 이고, 상기 알케미라 불가리스(Alchemilla vulgaris) 추출물의 함량은 약 3.0%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.Specifically, the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds is about 1.5% (w/v), and the content of the Alchemilla vulgaris extract is about 3.0% (w/v) may be, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 글리세린, 꿀, 히알루론산, 잔탄검, 콜라겐 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may further include one selected from the group consisting of glycerin, honey, hyaluronic acid, xanthan gum, collagen, and combinations thereof, but is not limited thereto. .
예를 들어, 상기 점막 상처 치료용 조성물은 글리세린, 꿀 및 히알루론산을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.For example, the composition for treating mucosal wounds may further include glycerin, honey and hyaluronic acid, but is not limited thereto.
구체적으로, 상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은 약 1.5%(w/v) 이고, 상기 알케미라 불가리스(Alchemilla vulgaris) 추출물의 함량은 약 3.0%(w/v) 이고, 상기 글리세린의 함량은 63%(w/v) 이고, 상기 꿀의 함량은 32%(w/v) 이고, 상기 히알루론산의 함량은 0.5%(w/v) 인 것일 수 있으나, 이에 제한되는 것은 아니다.Specifically, the content of the Saussurea pulchella (Fisch.) extract in the composition for treating mucosal wounds is about 1.5% (w/v), and the content of the Alchemilla vulgaris extract is about 3.0% (w/v), the content of the glycerin is 63% (w/v), the content of the honey is 32% (w/v), and the content of the hyaluronic acid is 0.5% (w/v) However, the present invention is not limited thereto.
본원에 따른 상기 점막 상처 치료용 조성물이 글리세린(Glycerol)을 포함하는 경우, 높은 보습효과로 통증을 완화할 수 있다.When the composition for treating mucosal wounds according to the present application contains glycerol, pain can be relieved with a high moisturizing effect.
또한, 높은 농도의 글리세린은 체내의 세포를 수축시켜 외부로 이동하는 삼출물을 조직 외부로 배출시킬 수 있다. 이때 글리세린은 높은 삼투압을 가지며, 폴리머의 형태로 결합력을 갖고 있기 때문에 조직 속으로 침투하지 않고 상처 외부에 존재한다. 따라서, 글리세린은 상기 식물성추출물과 결합하여 점도가 높아진 상태에서 상처 위에 필름막을 도포하게 된다. 따라서, 상기 조직 외부로 배출된 삼출물은 상기 식물성추출물의 탄닌(tannin)성분과 결합하여 체내 조직으로 다시 유입되지 않는다.In addition, the high concentration of glycerin can contract the cells in the body to discharge the exudate moving to the outside to the outside of the tissue. At this time, glycerin has a high osmotic pressure and because it has a binding force in the form of a polymer, it does not penetrate into the tissue and exists outside the wound. Therefore, glycerin is combined with the vegetable extract to apply a film film on the wound in a state in which the viscosity is increased. Therefore, the exudate discharged to the outside of the tissue is combined with the tannin component of the vegetable extract and does not flow back into the body tissue.
또한, 조직 밖으로 삼출물이 배출될 때 상처 내부의 바이러스 및 오염물질도 함께 배출되므로, 바이러스 및 오염물질을 제거할 수 있는 장점이 있다.In addition, since the virus and contaminants inside the wound are also discharged when the exudate is discharged out of the tissue, there is an advantage in that the virus and contaminants can be removed.
또한, 꿀(honey)은 점막에 도포 시 충분한 수분을 점막에 공급하고, 항박테리아 성분이 함유되어 있으므로, 상처 치유를 촉진할 수 있다.In addition, honey (honey) supplies sufficient moisture to the mucous membrane when applied to the mucous membrane, and contains an antibacterial component, so it can promote wound healing.
또한, 히알루론산(Hyaluronic Acid)은 N-아세틸글루코사민과 글루쿠론산으로 이루어진 고분자 화합물이다. 히알루론산은 조직을 재구축하고, 세포를 재생시키며, 세균의 침입이나 독물의 침투를 방지하여 상처의 오염 및 감염 확산을 방지함으로써 상처 치료를 촉진할 수 있다.In addition, hyaluronic acid (Hyaluronic Acid) is a high molecular compound consisting of N- acetylglucosamine and glucuronic acid. Hyaluronic acid can promote wound healing by reconstructing tissues, regenerating cells, and preventing contamination of the wound and the spread of infection by preventing invasion of bacteria or poisons.
또한, 콜라켄은 대부분 동물이나 사람에 있는 특히 피부, 근육과 힘줄과 같은 연결 조직에서 발견되는 섬유성 단백질로서. 상기 콜라겐은 혈액과 접촉할 때, 혈소판이 콜라겐에 응집하고 플라즈마와 함께 박리되는 응고인자를 유지하여 최종적으로 피브린과 혈전을 형성하여 지혈 작용을 할 수 있다.Collaken is also a fibrous protein found mostly in animals and humans, especially in the skin, connective tissues such as muscles and tendons. When the collagen is in contact with blood, platelets aggregate to the collagen and maintain coagulation factors that are peeled off together with the plasma, thereby finally forming a blood clot with fibrin to have a hemostatic effect.
또한, 콜라겐은 포함하는 경우, 수분증발을 억제하여 보습 상태를 유지하며, 밀도를 높여서 공기와의 차단효과를 증대시킴으로써 상처 치료 효과 및 통증 완화 효과를 증대 시킬 수 있다.또한, 잔탄검(Xanthan Gum)은 고분자 다당류인 검(Gum) 물질을 아이소프로필알코올에 정제·건조·분쇄한 분말 혼합물로, 물에 용해되어 본원에 따른 점막 상처 치료용 조성물의 점착성 및 점도를 증가시키는 증점제로 사용될 수 있다. In addition, when collagen is included, it suppresses moisture evaporation to maintain a moist state, and increases the density to increase the blocking effect from air, thereby increasing the wound healing effect and pain relief effect. In addition, Xanthan Gum (Xanthan Gum) ) is a powder mixture obtained by refining, drying, and pulverizing a high molecular weight polysaccharide gum in isopropyl alcohol, and is dissolved in water to increase the adhesion and viscosity of the composition for treating mucosal wounds according to the present invention. It can be used as a thickener.
본원에 따른 상기 점막 상처 치료용 조성물은 각시취(Saussurea pulchella (Fisch.)) 추출물을 유효성분으로 포함함으로써 항산화 및 항염증 효능을 가지고, 피부 상처에 도포하였을 때 글리세린의 높은 삼투압에 의해 피부 내부로부터 피부 상처에 삼출물을 배출시켜서 감염된 세균 및 기타 오염물질을 살균하고, 상기 히알루론산에 의해 세균 침투를 방지하여 상처의 감염을 방지하며, 허브 엑기스에 의해 세포 간 매트릭스를 파괴하는 단백질 분해효소를 중화시켜 매트릭스를 복구하고 박테리아 또는 바이러스성 단백질에 결합하여 감염 및 독성물질의 해방을 감소시켜 세포의 성장을 촉진하여 상처 치료를 촉진하며, 상기 글리세린과 함께 수분증발을 억제하여 보습상태를 유지하고, 꿀에 의해 피부에 도포시 상처부위에 충분한 수분을 공급과 함께 항 박테리아 성분에 의해 상처 치유를 촉진하게 된다.The composition for treating mucosal wounds according to the present application has antioxidant and anti-inflammatory effects by including Saussurea pulchella (Fisch.) extract as an active ingredient, Discharges exudate to skin wounds to sterilize infected bacteria and other contaminants, prevents infection of wounds by preventing bacterial penetration with the hyaluronic acid, and neutralizes proteolytic enzymes that destroy intercellular matrix with herbal extracts It restores the matrix and binds to bacterial or viral proteins to reduce the release of infection and toxic substances, promotes cell growth, promotes wound healing, and maintains moisture by inhibiting water evaporation with the glycerin, When applied to the skin, it supplies sufficient moisture to the wounded area and promotes wound healing by antibacterial ingredients.
본원의 일 구현예에 따르면, 상기 점막은 장 점막, 위 점막, 기도 점막, 피부 점막, 입과 구강의 점막, 비점막, 안구 점막, 귀 점막, 생식기 점막 및 항문 점막, 직장 점막 및 이들의 조합들로 이루어진 군으로부터 선택되는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the mucous membrane is intestinal mucosa, gastric mucosa, airway mucosa, skin mucosa, mouth and oral mucosa, nasal mucosa, eye mucosa, ear mucosa, genital mucosa and anal mucosa, rectal mucosa, and combinations thereof. It may be selected from the group consisting of, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 점막의 염증 장애 또는 염증 병소를 예방 또는 치료하는데 사용하기 위한 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may be for use in preventing or treating inflammatory disorders or inflammatory lesions of the mucosa, but is not limited thereto.
점막 조직의 손상은 염증으로 인해 발생할 수 있다. 예를 들어, 본원에 따른 점막 상처 치료용 조성물은 펄첼라민 G(Pulchellamin G) 를 유효성분으로 포함함으로써, 산화적 스트레스로 인한 손상으로부터의 세포보호효과를 나타내는 효소로 알려진 헤마틴 산화효소-1(HemeOxygenase-1, HO-1)의 발현 및 활성을 증가시키며, 염증을 직접적으로 유도할 수 있는 NO의 분비를 효과적으로 억제할 수 있고, 상기 NO의 분비 및 염증을 유발하는 염증과 관련된 사이토카인의 생성 및 활성화를 효과적으로 억제할 수 있다. 이는 점막의 염증 장애 또는 염증 병소를 치료하는 기전 중 하나로 작용할 수 있다. 이에, 본원에 따른 점막 상처 치료용 조성물은 염증으로 인해 발생한 점막 상처의 치료를 촉진할 수 있다.Damage to mucosal tissue can result from inflammation. For example, the composition for treating mucosal wounds according to the present application contains pulselamine G (Pulchellamin G) as an active ingredient, so that hematin oxidase-1 known as an enzyme exhibiting a cytoprotective effect from damage caused by oxidative stress Increases the expression and activity of (HemeOxygenase-1, HO-1), can effectively inhibit the secretion of NO, which can directly induce inflammation, and the secretion of NO and inflammation-related cytokines production and activation can be effectively inhibited. This may act as one of the mechanisms of treating inflammatory disorders or inflammatory lesions of the mucous membrane. Accordingly, the composition for treating mucosal wounds according to the present application can promote treatment of mucosal wounds caused by inflammation.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 장염(gastroenteritis), 허혈성 괴사(ischemic necroses), 장 점막 궤양(ulceration), 궤양성 대장염(ulcerative colitis; UC), 크론병(Crohn's disease; CD) 및 이들의 조합들로 이루어진 군으로부터 선택되는 것의 예방 또는 치료에 사용하기 위한 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds includes enteritis (gastroenteritis), ischemic necroses, intestinal mucosal ulceration (ulceration), ulcerative colitis (UC), Crohn's disease; CD) and combinations thereof, but may be for use in the prevention or treatment of those selected from the group consisting of, but is not limited thereto.
상기 장염, 허혈성 괴사, 장 점막 궤양, 궤양성 대장염, 크론병 등의 염증성 장 질환에서 가장 흔하고 주요한 증상은 점막의 손상이다. 점막의 손상은 염증으로 인해 발생한다.The most common and major symptom in inflammatory bowel diseases such as enteritis, ischemic necrosis, intestinal mucosal ulceration, ulcerative colitis, and Crohn's disease is damage to the mucous membrane. Damage to the mucous membrane is caused by inflammation.
본원에 따른 점막 상처 치료용 조성물은 펄첼라민 G(Pulchellamin G) 를 유효성분으로 포함함으로써 항산화 및 항염증 활성을 가진다. 이에, 염증으로 인해 발생한 점막 상처의 치료를 촉진함으로써, 상기 염증성 장 질환의 치료를 촉진할 수 있다.The composition for treating mucosal wounds according to the present application has antioxidant and anti-inflammatory activity by including Pulchellamin G as an active ingredient. Accordingly, by promoting the treatment of mucosal wounds caused by inflammation, it is possible to promote the treatment of the inflammatory bowel disease.
대장염은 대장에 염증이 발생하는 질환으로, 다양한 원인에 의해 발생하고, 테네스무스(tenesmus, 시원치 않음), 복부팽만감, 하복 부통, 설사 등이 주요 증상으로 나타나고, 분변 중에 점액, 고름이나 혈액이 섞이는 경우도 있다. 대장염은 원인에 따라 크게 감염성 대장염과 비감염성 대장염으로 구분될 수도 있고, 발병 기간에 따라 급성 대장염과 만성 대장염으로 구분될 수도 있다. 급성 대장염에는 아메바성이질, 세균성이질, 살모넬라나 항생물질에 의한 위막성 대장염(pseudomembranous enteritis) 등이 있고 만성 대장염에는 궤양성 대장염, 크론병, 결핵, 매독, X선 등에 의한 것이 있다. 또한, 대장염은 염증성 대장 질환(Inflammatory bowel disease;IBD) 뿐만아니라 과민성 대장염 증후군(irritable bowel syndrome, IBS)등을 포함한다. 염증성 대장 질환(Inflammatory bowel disease; IBD) 중 대표적인 질환인 궤양성 대장염(ulcerative colitis; UC)과 크론병(Crohn's disease; CD)은 아직 원인이 명확히 밝혀져 있지 않고 있으며, 복통과 더불어 심한 만성 설사와 혈성설사를 일으킬 수 있으며, 완치가 힘들고 호전과 악화를 반복하는 특성이 있다.Colitis is a disease that causes inflammation of the large intestine, and it occurs due to various causes. In some cases. Colitis may be largely divided into infectious colitis and non-infectious colitis according to the cause, and may be divided into acute colitis and chronic colitis according to the onset period. Acute colitis includes amoebic dysentery, bacterial dysentery, and pseudomembranous enteritis caused by salmonella or antibiotics, and chronic colitis includes ulcerative colitis, Crohn's disease, tuberculosis, syphilis, and X-rays. In addition, colitis includes irritable bowel syndrome (IBS) as well as inflammatory bowel disease (IBD). Ulcerative colitis (UC) and Crohn's disease (CD), which are representative diseases of inflammatory bowel disease (IBD), have not yet been clearly identified, and the causes of severe chronic diarrhea and bloody blood along with abdominal pain are still unknown. It can cause diarrhea, and it is difficult to cure and has the characteristic of repeating improvement and exacerbation.
궤양성 대장염 (ulcerative colitis, UC)은 대장의 점막에 진무름(미란)이나 궤양이 연속적으로 형성되는 질환으로, 혈변, 점혈변, 설사, 복통이 일어나고, 중증인 경우에는 발열, 체중감소, 빈혈 등의 전신성의 증상이 나타난다. 또한, 궤양성 대장염은 위장관 어느 부위에서도 발생할 수 있다. Ulcerative colitis (UC) is a disease in which erosions or ulcers are continuously formed on the mucous membrane of the large intestine. systemic symptoms of In addition, ulcerative colitis can occur anywhere in the gastrointestinal tract.
크론병은 입에서 항문에 이르는 소화관의 임의의 부위에 궤양 등의 병변이 비연속적으로 발생하는 질환으로서, 복통, 설사, 혈변과 더불어, 중증의 경우에는 탈수, 빈혈, 발열, 하혈, 체중감소, 전신권태감, 빈혈 등의 증상이 나타난다. Crohn's disease is a disease in which lesions such as ulcers occur discontinuously in any part of the digestive tract from the mouth to the anus. Symptoms such as general malaise and anemia appear.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 약학적으로 허용가능한 담체, 부형제, 희석제 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 추가 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds may further include one selected from the group consisting of pharmaceutically acceptable carriers, excipients, diluents, and combinations thereof, but is not limited thereto.
본원의 일 구현예에 따르면, 상기 담체, 부형제 및 희석제는, 각각 독립적으로, 락토즈, 덱스트로즈, 수크로즈, 올리고당, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘, 스테아레이트, 광물유 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the carrier, excipient and diluent are, each independently, lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin , calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium, stearate, mineral oil and combinations thereof. It may include, but is not limited to.
본원의 일 구현예에 따르면, 상기 점막 상처 치료용 조성물은 크림, 겔, 패치, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제, 카타플라스마제 및 이들의 조합들로 이루어진 군으로부터 선택되는 피부 외용제 형태로 투여되는 것일 수 있으나, 이에 제한되는 것은 아니다.According to one embodiment of the present application, the composition for treating mucosal wounds is selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, liniments, pastas, cataplasmases, and combinations thereof. It may be administered in the form of a selected skin external preparation, but is not limited thereto.
상기 각시취 추출물은 피하 경로, 근육내 경로, 정맥내 경로, 경막내 경로, 설하 경로, 볼점막 경로, 직장 경로, 질 경로, 안구 경로, 귀 경로, 코 경로, 흡입 경로, 분무 경로, 피부 경로, 경피 경로 및 이들의 조합들로 이루어진 군으로부터 선택되는 경로로 투여되는 것일 수 있으나, 이에 제한되는 것은 아니다.The extracts from each sagittal route are subcutaneous route, intramuscular route, intravenous route, intrathecal route, sublingual route, buccal route, rectal route, vaginal route, ocular route, ear route, nasal route, inhalation route, nebulization route, dermal route , may be administered by a route selected from the group consisting of transdermal routes and combinations thereof, but is not limited thereto.
투여량은, 이에 제한되지는 않으나 물질의 성질, 독성, 투여 대상의 종류, 연령, 체중 및 건강 등의 조건을 기초로 당업자가 판단하여 적절하게 결정할 수 있다.The dosage may be appropriately determined by a person skilled in the art based on conditions such as, but not limited to, the properties of the substance, toxicity, the type of administration target, age, weight, and health.
이하 실시예를 통하여 본 발명을 더욱 상세하게 설명하고자 하나, 하기의 실시예는 단지 설명의 목적을 위한 것이며 본원의 범위를 한정하고자 하는 것은 아니다.The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present application.
[실시예 1] [Example 1]
각시취(Saussurea pulchella (Fisch.)) 50 g 을 세척 및 분쇄하고, 열수(100℃ 이상 정제수) 1 Kg 으로 2 시간동안 추출하였다.50 g of each specimen (Saussurea pulchella (Fisch.)) was washed and pulverized, and extracted with 1 kg of hot water (purified water at 100° C. or higher) for 2 hours.
원재료 및 불순물 분리를 위하여 PP 필터로 1 차 여과하였다. 이어서, 감압농축기(Evaporator)로 농축하여, 300 g 의 농축액을 확보하였다.Primary filtration was performed with a PP filter to separate raw materials and impurities. Then, it was concentrated with an evaporator to obtain 300 g of a concentrated solution.
이어서, 안정성 개선을 위해 농축액을 PES 필터로 2 차 여과하였다.Then, the concentrate was filtered twice with a PES filter to improve stability.
이어서, 상기 2 차 여과된 농축 여과액 200 g + 1,3-BG 5% + 1,2-헥산디올 3% + 에칠헥실글리세린 0.05% 를 혼합하여, 각시취 추출물을 유효성분으로 포함하는 점막 상처 치료용 조성물 10 Kg 을 제조하였다.Then, 200 g of the second-filtered concentrated filtrate + 5% of 1,3-BG + 3% of 1,2-hexanediol + 0.05% of ethylhexylglycerin were mixed, and the mucosal wound containing the extract of each stencil as an active ingredient A therapeutic composition 10 kg was prepared.
[실시예 2][Example 2]
상기 실시예 1 의 점막 상처 치료용 조성물 1.5%(w/v) 에 알케미라 불가리스 잎 엑기스 3.0%(w/v), 글리세린 63.0wt%, 꿀 32%(w/v) 및 히알루론산 0.5%(w/v) 을 혼합한 후, 내부의 공기 압력을 낮춘 후 저어서 제조하였다.Alchemyra vulgaris leaf extract 3.0% (w/v), glycerin 63.0 wt%, honey 32% (w/v) and hyaluronic acid 0.5% ( w/v) was mixed, and stirred after lowering the internal air pressure.
[실험예 1][Experimental Example 1]
도 1 및 도 2 는 본원의 실시예 2 에서 제조한 점막 상처 치료용 조성물을 이용한 in vivo 조건에서의 점막 피부 상처 치료 효과를 측정한 결과를 나타낸 이미지이다.1 and 2 are images showing the results of measuring the mucosal skin wound treatment effect in vivo conditions using the composition for treating mucosal wounds prepared in Example 2 of the present application.
구체적으로, 미니 피그(Mini-Pig(Sus scrofa)) 모델에서 가상의 병변(지름 2 cm 원형)을 표시하고, 내시경점막하박리술을 시행하였다.Specifically, a virtual lesion (2 cm in diameter round) was marked in a mini-pig (Sus scrofa) model, and endoscopic submucosal dissection was performed.
이어서, 시술 이후 발생한 인공 궤양에 대하여 14 일 동안 실험군에는 상기 실시예 2 에서 제조한 점막 상처 치료용 조성물을 도포하고, 대조군에는 아무 것도 도포하지 않았다.Then, the composition for treating mucosal wounds prepared in Example 2 was applied to the experimental group for 14 days for artificial ulcers that occurred after the procedure, and nothing was applied to the control group.
14 일 이후, 식도, 위 및 대장을 적출하여 10% 중성 완충 포르말린 용액에 고정하여 육안으로 관찰(도 1)하고, 일정한 두께로 삭정한 다음, 일반적인 조직처리 과정을 거쳐 파라핀 포매 하여 4 ㎛ 의 조직 절편을 제작하였다. 이어서, H&E 염색을 실시하여 광학 현미경을 이용하여 조직병리학적 소견을 관찰(도 2)하였다.After 14 days, the esophagus, stomach, and large intestine were extracted, fixed in 10% neutral buffered formalin solution, observed with the naked eye (FIG. 1), cut to a certain thickness, and then paraffin-embedded through a general tissue treatment process to form a 4 μm tissue Sections were prepared. Then, H&E staining was performed and histopathological findings were observed using an optical microscope (FIG. 2).
이를 통하여, 본원에 따른 점막 상처 치료용 조성물을 도포한 경우, 대조군보다 염증으로 인한 손상이 적은 것을 확인할 수 있었다. 따라서, 본원의 실시예 2 에서 제조한 점막 상처 치료용 조성물이 식도 점막, 위 점막, 대장 점막에서 대조군에 비하여 현저한 점막 상처 치료 효과를 나타내는 것을 확인할 수 있었다.Through this, when the composition for treating mucosal wounds according to the present application was applied, it was confirmed that the damage due to inflammation was less than that of the control group. Therefore, it was confirmed that the composition for treating mucosal wounds prepared in Example 2 of the present application exhibited a significant mucosal wound healing effect on the esophageal mucosa, gastric mucosa, and colonic mucosa compared to the control group.
전술한 본원의 설명은 예시를 위한 것이며, 본원이 속하는 기술분야의 통상의 지식을 가진 자는 본원의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다.The above description of the present application is for illustration, and those of ordinary skill in the art to which the present application pertains will understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present application. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a dispersed form, and likewise components described as distributed may be implemented in a combined form.
본원의 범위는 상기 상세한 설명보다는 후술하는 특허청구범위에 의하여 나타내어지며, 특허청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본원의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present application is indicated by the following claims rather than the above detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included in the scope of the present application.

Claims (12)

  1. 각시취(Saussurea pulchella (Fisch.)) 추출물을 유효성분으로 포함하는,Gakshichwi (Saussurea pulchella (Fisch.)) comprising an extract as an active ingredient,
    점막 상처 치료용 조성물.A composition for treating mucosal wounds.
  2. 제 1 항에 있어서, The method of claim 1,
    상기 점막 상처 치료용 조성물은 펄첼라민 G(Pulchellamin G) 를 유효성분으로 포함하는 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds is a composition for treating mucosal wounds comprising Pulchellamin G as an active ingredient.
  3. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물 중 상기 각시취(Saussurea pulchella (Fisch.)) 추출물의 함량은0.5%(w/v) 내지 50%(w/v) 인 것인, 점막 상처 치료용 조성물.The content of the extract of Saussurea pulchella (Fisch.) in the composition for treating mucosal wounds is 0.5% (w/v) to 50% (w/v) of the composition for treating mucosal wounds.
  4. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물은 알케미라 불가리스(Alchemilla vulgaris), 비티스 비니페라(Vitis vinifera), 카멜리아 시넨시스(Camellia sinensis), 바시니움 에스피(Vaccinium sp.), 바시니움 미르티루스(Vaccinoum myrtillus), 미모사 테누이플로라(Mimosa tenuiflora), 에키나세아 프르푸라(Echinacea purpura) 및 이들의 조합들로 이루어진 군으로부터 선택되는 것의 식물성추출물을 추가 포함하는 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds is Alchemilla vulgaris, Vitis vinifera, Camellia sinensis, Vaccinium sp., Vaccinium myrtirus (Vaccinoum). myrtillus), mimosa tenuiflora (Mimosa tenuiflora), Echinacea purpura (Echinacea purpura), and a composition for treating mucosal wounds further comprising a plant extract of those selected from the group consisting of combinations thereof.
  5. 제 4 항에 있어서,5. The method of claim 4,
    상기 점막 상처 치료용 조성물 중 상기 식물성추출물의 함량은 2%(w/v) 내지 5%(w/v) 인 것인, 점막 상처 치료용 조성물.The content of the vegetable extract in the composition for treating mucosal wounds is 2% (w/v) to 5% (w/v) of the composition for treating mucosal wounds.
  6. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물은 글리세린, 꿀, 히알루론산, 잔탄검, 콜라겐 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 추가 포함하는 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds further comprises one selected from the group consisting of glycerin, honey, hyaluronic acid, xanthan gum, collagen, and combinations thereof.
  7. 제 1 항에 있어서,The method of claim 1,
    상기 점막은 장 점막, 위 점막, 기도 점막, 피부 점막, 입과 구강의 점막, 비점막, 안구 점막, 귀 점막, 생식기 점막 및 항문 점막, 직장 점막 및 이들의 조합들로 이루어진 군으로부터 선택되는 것인, 점막 상처 치료용 조성물.The mucous membrane is selected from the group consisting of intestinal mucosa, gastric mucosa, airway mucosa, skin mucosa, oral and oral mucosa, nasal mucosa, eye mucosa, ear mucosa, genital and anal mucosa, rectal mucosa, and combinations thereof. , a composition for treating mucosal wounds.
  8. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물은 점막의 염증 장애 또는 염증 병소를 예방 또는 치료하는데 사용하기 위한 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds is for use in preventing or treating inflammatory disorders or inflammatory lesions of the mucous membrane, compositions for treating mucosal wounds.
  9. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물은 장염(gastroenteritis), 허혈성 괴사(ischemic necroses), 장 점막 궤양(ulceration), 궤양성 대장염(ulcerative colitis; UC), 크론병(Crohn's disease; CD) 및 이들의 조합들로 이루어진 군으로부터 선택되는 것의 예방 또는 치료에 사용하기 위한 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds includes enteritis (gastroenteritis), ischemic necroses, intestinal mucosal ulceration (ulceration), ulcerative colitis (UC), Crohn's disease (CD), and combinations thereof. For use in the prevention or treatment of those selected from the group consisting of, a composition for treating mucosal wounds.
  10. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물은 약학적으로 허용가능한 담체, 부형제, 희석제 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 추가 포함하는 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds further comprises a pharmaceutically acceptable carrier, excipient, diluent, and combinations thereof.
  11. 제 10 항에 있어서,11. The method of claim 10,
    상기 담체, 부형제 및 희석제는, 각각 독립적으로, 락토즈, 덱스트로즈, 수크로즈, 올리고당, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘, 스테아레이트, 광물유 및 이들의 조합들로 이루어진 군으로부터 선택되는 것을 포함하는 것인, 점막 상처 치료용 조성물.The carrier, excipient and diluent are, each independently, lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium, stearate, mineral oil, and combinations thereof. A composition for the treatment of wounds.
  12. 제 1 항에 있어서,The method of claim 1,
    상기 점막 상처 치료용 조성물은 크림, 겔, 패치, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제, 카타플라스마제 및 이들의 조합들로 이루어진 군으로부터 선택되는 피부 외용제 형태로 투여되는 것인, 점막 상처 치료용 조성물.The composition for treating mucosal wounds is administered in the form of an external preparation for the skin selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, liniments, pastas, cataplasmas, and combinations thereof. The composition for treating mucosal wounds.
PCT/KR2021/014211 2020-10-22 2021-10-14 Composition for preventing and treating mucosal damage WO2022086047A1 (en)

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