KR102474229B1 - Composition for increasing salivary secretion or prevention or treatment of xerostomia comprising phytosterols - Google Patents
Composition for increasing salivary secretion or prevention or treatment of xerostomia comprising phytosterols Download PDFInfo
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- KR102474229B1 KR102474229B1 KR1020170162217A KR20170162217A KR102474229B1 KR 102474229 B1 KR102474229 B1 KR 102474229B1 KR 1020170162217 A KR1020170162217 A KR 1020170162217A KR 20170162217 A KR20170162217 A KR 20170162217A KR 102474229 B1 KR102474229 B1 KR 102474229B1
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- present
- secretion
- enhancing
- active ingredient
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
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- A23V2200/312—Foods, ingredients or supplements having a functional effect on health having an effect on dental health
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Abstract
본 발명은 식물성스테롤(Phytosterols)을 유효성분으로 함유하는 타액 분비 증강 또는 구강건조증 예방 또는 치료용 조성물에 대한 것으로, 보다 상세하게는 β-sitosterol, stigmasterol, campesterol, 및 fucosterol 중에서 하나 이상을 유효성분으로 함유하는 타액 분비 증강 또는 구강건조증 예방 또는 치료용 조성물에 대한 것이다.
본 발명의 식물성스테롤은 타액 분비 기전의 주요 인자인 세포 내 칼슘 이온의 농도를 증가시켜 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료에 우수한 효과를 보인다. 따라서 본 발명은 천연물이므로 부작용 없이 안전하게 사용될 수 있으며, 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료에 탁월한 효과를 보이는 조성물을 제공할 수 있다.The present invention relates to a composition for enhancing salivary secretion or preventing or treating xerostomia containing plant sterols as an active ingredient, and more specifically, at least one of β-sitosterol, stigmasterol, campesterol, and fucosterol as an active ingredient It relates to a composition for enhancing salivary secretion or preventing or treating xerostomia.
The plant sterols of the present invention increase the concentration of intracellular calcium ions, which is a major factor in the secretion mechanism of saliva, and show excellent effects in enhancing salivary secretion or preventing, improving, or treating xerostomia. Therefore, since the present invention is a natural product, it can be safely used without side effects, and can provide a composition that exhibits excellent effects in preventing, improving, or treating dry mouth or enhancing salivary secretion.
Description
본 발명은 식물성스테롤(Phytosterols)을 유효성분으로 함유하는 타액 분비 증강 또는 구강건조증 예방 또는 치료용 조성물에 대한 것으로, 보다 상세하게는 β-sitosterol, stigmasterol, campesterol, 및 fucosterol 중에서 하나 이상을 유효성분으로 함유하는 타액 분비 증강 또는 구강건조증 예방 또는 치료용 조성물에 대한 것이다. The present invention relates to a composition for enhancing salivary secretion or preventing or treating xerostomia containing plant sterols as an active ingredient, and more specifically, at least one of β-sitosterol, stigmasterol, campesterol, and fucosterol as an active ingredient It relates to a composition for enhancing salivary secretion or preventing or treating xerostomia.
타액은 타액선에서 구강으로 분비되는 분비액으로 정상인의 경우 일일 평균1~1.5 L의 타액이 생성된다. 타액의 약 99.5 %는 수분이며 나머지 0.5 %는 전해질, 점액소, 당단백질, 효소, 항균성 물질 등으로 구성된다. 타액은 구강 점막을 윤활하게 하고 구강조직을 보호하며, 소화, 미각, 치아의 재무기물화(remineralization)등에 관여한다. 특히, 타액에 존재하는 여러 단백질들은 항박테리아, 항바이러스와 항곰팡이 작용으로 구강미생물총(oral microbiota)에 지대한 영향을 미친다(Journal of Dentistry 33:223-233, 2005).Saliva is a secretion fluid secreted from the salivary glands into the oral cavity. In the case of a normal person, an average of 1 to 1.5 L of saliva is produced per day. About 99.5% of saliva is water, and the remaining 0.5% is composed of electrolytes, mucins, glycoproteins, enzymes, and antimicrobial substances. Saliva lubricates the oral mucosa, protects oral tissues, and is involved in digestion, taste, and remineralization of teeth. In particular, several proteins present in saliva exert a great influence on the oral microbiota with antibacterial, antiviral and antifungal actions (Journal of Dentistry 33:223-233, 2005).
타액 분비기전은 단백질분비와 액체와 전해질의 분비로 나눌 수 있다. 분비종말부세포의 바닥가쪽 세포막에 존재하는 β-adrenergic receptor에 교감신경전달물질인 norepinephrine이 결합함으로써 heterotrimeric G-protein과 adenylyl cyclase가 활성화된다. 이로 인해 cyclic adenosine monophosphate의 형성이 촉매되어 protein kinase A가 활성화되면, 세포막에 존재하는 분비과립들이 세포외유출 방법으로 단백질을 내강쪽으로 분비하게 된다. 한편 액체와 전해질의 분비는 muscarinic cholinergic receptor에 부교감신경전달물질인 acetylcholine의 결합에 의해 주로 일어난다. Muscarinic receptor agonist가 이 수용체에 결합하게 되면 heterotrimeric G-protein과 phospholipase C가 차례로 활성화되어 궁극적으로 inositol triphosphate(IP₃)의 형성이 촉진된다. Inositol triphosphate(IP₃)는 세포 내에 저장되어 있는 Ca2+을 방출하고, 증가된 Ca2의 농도에 의해 내강쪽에 존재하는Cl- 통로와 바닥가쪽에 존재하는 K+ 통로가 열려 Na+/K+/2Cl- co-transporter가 활성화된다. 또한 소낭에 존재하는 aquaporin 5(AQP5) 단백질이 내강쪽 세포막으로 이동한다. 증가된 내강쪽의 Cl-은 폐쇄연접을 통해 내강으로 이동하는 Na+을 따라 균형을 맞추고 그 결과 삼투압기울기(osmotic gradient)가 발생한다. 삼투압기울기는 aquaporin 5(AQP5)와 폐쇄연접을 통해 물을 세포에서 내강쪽으로 이동시킨다(Annual Review of Physiology 67:445-469, 2005). Salivary secretion can be divided into protein secretion and fluid and electrolyte secretion. Heterotrimeric G-protein and adenylyl cyclase are activated by the binding of norepinephrine, a sympathetic neurotransmitter, to the β-adrenergic receptor present in the basolateral cell membrane of secretory terminal cells. This catalyzes the formation of cyclic adenosine monophosphate, and when protein kinase A is activated, the secretory granules present in the cell membrane secrete proteins into the lumen through exocytosis. On the other hand, the secretion of fluid and electrolytes is mainly caused by the binding of acetylcholine, a parasympathetic neurotransmitter, to muscarinic cholinergic receptors. When a muscarinic receptor agonist binds to this receptor, heterotrimeric G-protein and phospholipase C are activated in turn, ultimately promoting the formation of inositol triphosphate (IP₃). Inositol triphosphate (IP₃) releases Ca 2+ stored in cells, and the increased concentration of Ca 2 opens the Cl - channel in the luminal side and the K + channel in the basal side to open Na + /K + /2Cl - co-transporter is activated. In addition, the aquaporin 5 (AQP5) protein present in the vesicle migrates to the luminal cell membrane. The increased luminal Cl - balances the Na + moving into the lumen through the closed junction, resulting in an osmotic gradient. The osmotic gradient moves water from the cell to the lumen through aquaporin 5 (AQP5) and closed junctions (Annual Review of Physiology 67:445-469, 2005).
한편, aquaporin은 물 통로 단백질로서 각막, 신장, 간, 피부 등에서 발견된다. Aquaporin은 AQP0~12까지 subfamily가 다양하게 존재하는데, aquaporin 5는 타액 분비에 주요 biomarker이다. 특히, AQP5 knockout mice에서 타액 분비량이 60 % 이상 감소했다는 연구결과가 발표된 바 있다(The Journal of Biological Chemistry, 274: 20071-20074, 1999).On the other hand, aquaporin is a water passage protein found in the cornea, kidney, liver, and skin. Aquaporins exist in various subfamilies from AQP0 to AQP12, and aquaporin 5 is a major biomarker for salivary secretion. In particular, a research result was reported that salivary secretion decreased by more than 60% in AQP5 knockout mice (The Journal of Biological Chemistry, 274: 20071-20074, 1999).
타액선은 다양한 질병에 의해서 영향을 받는다. Cytomegalovirus, Epstein-Barr virus 및 Human herpes virus 등의 바이러스는 타액선세포를 감염시킨다. 당뇨병은 타액선의 기능을 떨어트려 타액 분비를 감소시키며, 타액의 포도당이 증가하면 치태대사에 악영향을 미친다. 쇼그렌 증후군(Sjogren’syndrome)과 류마티스관절염 또한 타액선 조직을 파괴하며, 부신질환은 타액 내 전해질 조성을 변화시킨다. 이외에도 후천성면역결핍증(acquired immune deficiency syndrome), 림프상피낭종(lymphoepithelial cyst), 림프절병증(lymphadenopathy), 낭종섬유증(cystic fibrosis) 환자의 타액선에서 병리적 변화가 관찰된다 (Ten Cate’Oral Biology, 8th ed, St Louis, MO: Mosby; 2013)The salivary glands are affected by various diseases. Viruses such as cytomegalovirus, Epstein-Barr virus and human herpes virus infect salivary gland cells. Diabetes reduces salivary secretion by reducing the function of the salivary glands, and when glucose in saliva increases, it adversely affects plaque metabolism. Sjogren's syndrome and rheumatoid arthritis also destroy salivary gland tissue, and adrenal disease alters the electrolyte composition in saliva. In addition, pathological changes are observed in the salivary glands of patients with acquired immune deficiency syndrome, lymphoepithelial cyst, lymphadenopathy, and cystic fibrosis (Ten Cate'Oral Biology, 8 th ed, St Louis, MO: Mosby; 2013)
구강건조증(Xerostomia)은 타액선과 관련하여 가장 흔한 임상적 증상이다. 비자극시에 분비되는 타액의 양이 분당 0.1 mL 이하인 경우 구강건조증으로 진단된다. 구강건조증의 발병원인은 주로 항우울증, 항당뇨, 항알레르기 등 다양한 약물의 부작용이다. 자연 노화에 의한 구강건조증은 타액선의 실질조직이 감소하고 지방조직으로 대체되거나 샘꽈리 용적이 감소하여 나타난다. 또한, 자가면역질환인 쇼그렌 증후군이나 방사선 치료에 의해 타액선이 파괴되거나 타액선의 혈류가 차단되어 나타나기도 한다. 구강 내 타액 양이 감소되면 충치, 산식증(acid erosion), 구강칸디다증(oral candidiasis), 미각장애(dysgeusia), 연하곤란(dysphagia), 구강 감각장애(oral dysesthesia), 구취(intraoral halitosis) 등이 동반된다(The Journal of the American Dental Association, 138: S15-S20, 2007).Xerostomia is the most common clinical symptom associated with the salivary glands. When the amount of saliva secreted during non-stimulation is less than 0.1 mL per minute, xerostomia is diagnosed. The causes of xerostomia are mainly side effects of various drugs such as antidepressants, antidiabetics, and antiallergics. Xerostomia due to natural aging is caused by a decrease in the parenchymal tissue of the salivary gland, which is replaced by adipose tissue, or a decrease in the volume of the acinar gland. In addition, salivary glands are destroyed by Sjogren's syndrome, an autoimmune disease, or radiation therapy, or blood flow to the salivary glands is blocked. When the amount of saliva in the mouth is reduced, tooth decay, acid erosion, oral candidiasis, dysgeusia, dysphagia, oral dysesthesia, and intraoral halitosis occur. (The Journal of the American Dental Association, 138: S15-S20, 2007).
현재 사용되고 있는 대표적인 구강건조증 치료제는 부교감신경작용제(parasympathomimetic)인 필로카르핀(pilocarpine), 세비멜린(cevimeline), 베탄콜(bethanechol) 등이 있다. 하지만 이러한 치료제들은 발한, 구토, 혈관확장, 설사, 기관지경련(bronchospasm)과 같은 부작용을 유발시키는 단점이 있다. 따라서 적은 부작용과 높은 안전성의 특징을 지닌 천연물을 기반으로 하여 구강건조증을 예방하고 치료하는 것은 매우 중요한 과제이다.Representative xerostomia treatments currently used include parasympathomimetics such as pilocarpine, cevimeline, and betanchol. However, these treatments have the disadvantage of causing side effects such as sweating, vomiting, vasodilation, diarrhea, and bronchospasm. Therefore, it is a very important task to prevent and treat xerostomia based on natural products with low side effects and high safety.
식물성스테롤(Phytosterols)은 식물에서 자연적으로 얻을 수 있는 스테로이드 알코올계의 피토케미컬(phytochemicals)로, 대표적으로 β-sitosterol, stigmasterol, campesterol, fucosterol 등이 있다. β-Sitosterol은 현재까지 항균(Natural Product Research, 22: 1085-1093, 2008), 항염(Journal of Ethnopharmacology, 116: 263-269, 2008), 항암(Acta Pharmacologica Sinica, 29: 341-348, 2008), 항당뇨(Journal of Diabetes, 3(1): 29-37, 2011), 항동맥경화(Atherosclerosis, 226(1): 110-117, 2013) 등의 활성이 보고 된 바 있다. Fucosterol은 해조류에 많이 함유되어 있는 물질이며, 항암(Pharmacognosy Magazine, 8(29): 60-64, 2012), 항당뇨(Archives of Pharmacal Research, 27(11): 1120-1122, 2004), 항산화(Bioorganic & Medicinal Chemistry, 17(5): 1963-1973, 2009), 혈중 지질 성분 개선(Biochemical and Biophysical Research Communications, 369(2): 363-368, 2008) 등의 효과가 알려져 있다. Plant sterols (Phytosterols) are phytochemicals of steroidal alcohols that can be obtained naturally from plants, and representatively include β-sitosterol, stigmasterol, campesterol, and fucosterol. β-Sitosterol has been found to be antibacterial (Natural Product Research, 22: 1085-1093, 2008), anti-inflammatory (Journal of Ethnopharmacology, 116: 263-269, 2008), and anticancer (Acta Pharmacologica Sinica, 29: 341-348, 2008). , Anti-diabetes (Journal of Diabetes, 3(1): 29-37, 2011), anti-atherosclerosis (Atherosclerosis, 226(1): 110-117, 2013) have been reported. Fucosterol is a substance that is abundant in seaweed and has anticancer (Pharmacognosy Magazine, 8(29): 60-64, 2012), antidiabetic (Archives of Pharmacal Research, 27(11): 1120-1122, 2004), antioxidant ( Bioorganic & Medicinal Chemistry, 17(5): 1963-1973, 2009), blood lipid component improvement (Biochemical and Biophysical Research Communications, 369(2): 363-368, 2008), etc. effects are known.
Stigmasterol과 campesterol은 항골관절염(Osteoarthritis and Cartilage, 18(1): 106-116, 2010), 갑상선 억제 및 항산화(Fitoterapia, 80(2): 123-126, 2009), 콜레스테롤 감소(Australian Family Physicians, 38(4): 218-221, 2009) 등의 효과가 알려져 있다.Stigmasterol and campesterol are anti-osteoarthritis (Osteoarthritis and Cartilage, 18(1): 106-116, 2010), thyroid suppression and antioxidant (Fitoterapia, 80(2): 123-126, 2009), cholesterol reduction (Australian Family Physicians, 38 (4): 218-221, 2009) and the like are known.
그러나 본 발명의 이전에는 식물스테롤(phytosterols)의 구강건조증 예방, 개선 혹은 치료 효과에 대해서는 상세히 보고된 바 없다. However, prior to the present invention, there has been no detailed report on the preventive, ameliorative, or therapeutic effects of phytosterols on xerostomia.
이에 본 발명자들은 타액 분비 증강에 부작용 없이 안전하게 적용될 수 있는 천연물을 탐색하기 위하여 연구한 결과, 식물스테롤(phytosterols)이 타액 분비 마커인 아쿠아스포린 발현량을 증가시켜, 구강건조증 예방, 개선 및 치료 효과가 있음을 확인하여 본 발명을 완성하였다. Accordingly, the present inventors studied to search for natural products that can be safely applied to the enhancement of salivary secretion without side effects. As a result, phytosterols increase the expression level of aquasporin, a marker for salivary secretion, and thus prevent, improve, and treat dry mouth. It was confirmed that the present invention was completed.
따라서 본 발명의 목적은Therefore, the object of the present invention is
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 타액 분비 증강용 약학적 조성물을 제공하는 것이다. It is to provide a pharmaceutical composition for enhancing saliva secretion containing plant sterols (pnytosterols) as an active ingredient.
본 발명의 다른 목적은Another object of the present invention is
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 타액 분비 증강용 식품 조성물을 제공하는 것이다. It is to provide a food composition for enhancing saliva secretion containing plant sterols (pnytosterols) as an active ingredient.
본 발명의 또 다른 목적은Another object of the present invention is
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 구강 건조증 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is to provide a pharmaceutical composition for preventing or treating xerostomia comprising plant sterols (pnytosterols) as an active ingredient.
본 발명의 또 다른 목적은Another object of the present invention is
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 구강 건조증 예방 또는 개선용 식품 조성물을 제공하는 것이다.To provide a food composition for preventing or improving dry mouth containing plant sterols (pnytosterols) as an active ingredient.
본 발명의 또 다른 목적은Another object of the present invention is
식물성스테롤을 유효성분으로 포함하는 타액 분비 증강용; 또는 구강건조증 예방 또는 개선용; 의약외품 조성물 및 의약외품을 제공하는 것이다.For enhancing saliva secretion containing plant sterols as an active ingredient; or for preventing or improving dry mouth; It is to provide quasi-drug compositions and quasi-drugs.
상기와 같은 목적을 달성하기 위하여 본 발명은 In order to achieve the above object, the present invention
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 타액 분비 증강용 약학적 조성물을 제공한다. Provided is a pharmaceutical composition for enhancing saliva secretion comprising plant sterols (pnytosterols) as an active ingredient.
본 발명의 다른 목적을 달성하기 위하여 본 발명은In order to achieve another object of the present invention, the present invention
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 타액 분비 증강용 식품 조성물을 제공한다. It provides a food composition for enhancing saliva secretion containing plant sterols (pnytosterols) as an active ingredient.
본 발명의 또 다른 목적을 달성하기 위하여 본 발명은In order to achieve another object of the present invention, the present invention
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 구강 건조증 예방 또는 치료용 약학적 조성물을 제공한다.Provided is a pharmaceutical composition for preventing or treating xerostomia, comprising plant sterols (pnytosterols) as an active ingredient.
본 발명의 또 다른 목적을 달성하기 위하여 본 발명은In order to achieve another object of the present invention, the present invention
식물성스테롤(pnytosterols)을 유효성분으로 포함하는 구강 건조증 예방 또는 개선용 식품 조성물을 제공한다.Provided is a food composition for preventing or improving dry mouth containing plant sterols (pnytosterols) as an active ingredient.
본 발명의 또 다른 목적을 달성하기 위하여 본 발명은In order to achieve another object of the present invention, the present invention
식물성스테롤을 유효성분으로 포함하는 타액 분비 증강용; 또는 구강건조증 예방 또는 개선용; 의약외품 조성물 및 의약외품을 제공한다.For enhancing saliva secretion containing plant sterols as an active ingredient; or for preventing or improving dry mouth; Provided are quasi-drug compositions and quasi-drugs.
이하 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 식물성스테롤(pnytosterols)을 유효성분으로 포함하는 타액 분비 증강용 조성물을 제공한다. The present invention provides a composition for enhancing saliva secretion comprising plant sterols (pnytosterols) as an active ingredient.
본 발명의 "식물성스테롤(phytosterol)"은 통상의 모든 종류의 식물에서 유래되는 스테롤 물질에 대한 통칭으로서, 주로 식물성 기름을 고온 진공하에서 최종 탈취하는 과정에서 발생하는 증류성분으로부터 분리, 정제하여 만든다. The "phytosterol" of the present invention is a general term for sterol substances derived from all kinds of conventional plants, and is mainly made by separating and refining vegetable oil from distillation components generated in the final deodorizing process under high temperature vacuum.
본 발명의 식물성스테롤은 그 종류가 제한되지 않으나, 바람직하게는 베타-시토스테롤, 푸코스테롤, 스티그마스테롤 또는 캠페스테롤일 수 있다.The plant sterol of the present invention is not limited in its kind, but may preferably be beta-sitosterol, fucosterol, stigmasterol or campesterol.
상기 베타-시토스테롤(β-sitosterol)은 하기 화학식 1로 표시된다. 상기 β-sitosterol은 현미, 콩류, 땅콩, 무, 또는 배추 등의 추출물로부터 분리된 것일 수 있으며, 바람직하게는 현미, 콩류, 땅콩, 무, 배추 등을 이용한 에탄올 추출물, 열수 추출물, 헥산 추출물, 에틸아세테이트 추출물, 초고압 추출물에서 분리, 정제된 것일 수 있다. The beta-sitosterol (β-sitosterol) is represented by
[화학식 1][Formula 1]
상기 스티그마스테롤(stigmasterol)은 하기 화학식 2로 표시된다. 상기 stigmasterol은 대두, 강낭콩, 완두, 또는 팥 등의 추출물로부터 분리된 것일 수 있으며, 바람직하게는 대두, 강낭콩, 완두, 팥 등을 이용한 에탄올 추출물, 열수 추출물, 헥산 추출물, 에틸아세테이트 추출물, 초고압 추출물에서 분리, 정제된 것일 수 있다. The stigmasterol is represented by
[화학식2][Formula 2]
상기 캠페스테롤(campesterol)은 하기 화학식 3으로 표시된다. 상기 campesterol은 대두, 시트로넬라(citronella), 자몽, 고추 등의 추출물로부터 분리된 것일 수 있으며, 바람직하게는 대두식물 종자, 시트로넬라(citronella), 자몽, 고추 등을 이용한 에탄올 추출물, 열수 추출물, 헥산 추출물, 에틸아세테이트 추출물, 초고압 추출물로부터 분리된 것일 수 있다. The campesterol is represented by
[화학식 3][Formula 3]
상기 푸코스테롤(fucosterol)은 하기 화학식 4로 표시된다. 상기 fucosterol은 모자반, 톳, 감태, 곰피 등의 추출물로부터 분리된 것일 수 있으며, 바람직하게는 모자반, 톳, 감태, 곰피 등을 이용한 에탄올 추출물, 열수 추출물, 헥산 추출물, 에틸아세테이트 추출물, 초고압 추출물일 수 있다. The fucosterol is represented by
[화학식 4][Formula 4]
상기 추출용매는 물, 유기용매, 아임계 유체 및 초임계 유체로 이루어진 군에서 선택된 하나 이상 일 수 있다. 상기 유기용매는 극성용매, 비극성 용매, 극성 및 비극성 혼합용매 또는 물 일수 있다. 구체적으로, 탄소수 1 내지 6의 알코올(alcohol), 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌 클로라이드(methylene chloride), 헥산(hexane), 시클로헥산(cyclohexane), 석유에테르(petroleum ether) 및 물로 이루어진 군에서 선택된 어느 하나 일 수 있다.The extraction solvent may be one or more selected from the group consisting of water, an organic solvent, a subcritical fluid, and a supercritical fluid. The organic solvent may be a polar solvent, a non-polar solvent, a mixture of polar and non-polar solvents, or water. Specifically, alcohol having 1 to 6 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane ), cyclohexane, petroleum ether, and water.
또한, 상기 식물성스테롤은 식물 추출물로부터 분리·정제하거나 화학적으로 합성하여 이용하거나, 시판되고 있는 화합물을 이용할 수 있다. 상기 식물스테롤의 화학적 합성 방법은 당업계에 공지된 일반적인 방법을 이용할 수 있다.In addition, the plant sterols may be separated/purified from plant extracts, chemically synthesized and used, or commercially available compounds may be used. The chemical synthesis method of the plant sterol may use a general method known in the art.
본 명세서에서, '타액(saliva)'이란 침이라고도 하며, 입속의 침샘(타액선)에서 분비되는 무색의 점성의 소화액을 의미한다. 일반적인 경우, 정상인에서 24시간 동안 분비되는 침의 양은 약 1000 ~ 1500㎖이다. 보통, 자율신경에 의해 자극받지 않았을 경우 1 분당 0.001~0.2㎖를 생성하며, 자극을 받으면 분당 0.18~1.7㎖로 유출량이 증가하는데, 분당 평균 분비량이 1㎖ 정도이다. 약 99%가 수분이며, 다양한 무기물을 포함하고 있다.In the present specification, 'saliva' is also referred to as saliva, and refers to a colorless, viscous digestive fluid secreted from the salivary glands (salivary glands) in the mouth. In general, the amount of saliva secreted for 24 hours in a normal person is about 1000 to 1500 ml. Normally, when not stimulated by the autonomic nerve, 0.001 to 0.2 ml per minute is produced, and when stimulated, the output increases to 0.18 to 1.7 ml per minute, with an average secretion of about 1 ml per minute. It is about 99% water and contains various minerals.
본 발명에서는 타액분비가 정상보다 적은 증상을 개선할 수 있다는 측면에서, 타액분비 증강용 조성물일 수 있다.In the present invention, in terms of improving symptoms of less than normal salivary secretion, it may be a composition for enhancing salivary secretion.
또한, 본 발명은 식물성스테롤(pnytosterols)을 유효성분으로 포함하는 구강 건조증 예방, 치료 또는 개선용 조성물을 제공한다.In addition, the present invention provides a composition for preventing, treating or improving xerostomia comprising plant sterols (pnytosterols) as an active ingredient.
본 발명의 '구강건조' 또는 '구강건조증'이란 침 분비가 줄어들거나 그 외에 다양한 원인에 의하여 입안이 마르는 증상을 의미한다. 구체적으로 24시간 분비되는 침의 양이 1000 ~ 1500㎖ 미만인 경우 입이 건조하고 마른다고 느끼거나, 입으로 숨을 쉬면서 입 안의 수분이 증발되어 구강이 건조하다고 느낄 수 있다.'Dry mouth' or 'dry mouth syndrome' of the present invention refers to a symptom in which saliva secretion is reduced or the mouth is dry due to various other causes. Specifically, if the amount of saliva secreted for 24 hours is less than 1000 to 1500 ml, the mouth may feel dry and dry, or the moisture in the mouth may evaporate while breathing through the mouth and the mouth may feel dry.
상기 '구강건조'는 쇼그렌 증후군, 만성염증성질환, 방사선 치료 또는 이에 의한 타액선 장해, 중증설사, 전신성 수분감소, 당뇨병, 영양소 결핍, 노화, 신경계 질환, 항암제 투여의 부작용 및 항당뇨, 항우울 또는 항알레르기성 약물의 부작용으로 이루어진 군에서 선택된 하나 이상의 원인에 의하여 유발된 것 일 수 있다.The 'dry mouth' refers to Sjogren's syndrome, chronic inflammatory disease, radiation therapy or salivary gland disorder caused by it, severe diarrhea, systemic water loss, diabetes, nutrient deficiency, aging, nervous system disease, side effects of anticancer drug administration, and antidiabetic, antidepressant or anticancer drugs. It may be caused by one or more causes selected from the group consisting of side effects of allergic drugs.
본 명세서에서, '예방'은 질병 또는 병증의 발병을 억제하거나 지연시키는 모든 행위를 의미한다. 본 발명에 있어서는 타액선의 타액 분비작용을 활성화하여 타액선 이상, 타액선의 기능저하, 위축 또는 다른 원인에 의하여 타액분비가 감소되는 증상의 발현 시기를 지연시키거나, 발병을 억제하는 것을 의미한다.In this specification, 'prevention' refers to any action that suppresses or delays the onset of a disease or condition. In the present invention, by activating the salivary secretion action of the salivary gland, it means to delay the onset of the symptoms of salivary secretion reduction due to salivary gland abnormality, functional decline, atrophy or other causes, or to suppress the onset.
본 명세서에서, '개선'은 질병 또는 병증 상태를 호전 또는 이롭게 변경하는 모든 행위를 의미하는 것으로, 본 발명에 있어서는 타액선의 타액 분비작용을 활성화하여 타액선 이상, 타액선의 기능저하, 위축 또는 다른 원인에 의하여 타액분비가 감소되어 나타나는 구강 건조, 입마름 증상을 호전시키는 것을 의미한다.In the present specification, 'improvement' refers to any action that improves or beneficially changes a disease or condition, and in the present invention, the salivary secretion of the salivary glands is activated to treat abnormalities of the salivary glands, functional decline of the salivary glands, atrophy, or other causes. It means that it improves the symptoms of dry mouth and dry mouth caused by decreased salivary secretion.
본 명세서에서, '치료'는 질병 또는 병증의 진행을 지연, 중단 또는 역전시키는 모든 행위를 의미하는 것으로, 본 발명에 있어서는 타액선의 타액 분비작용을 활성화하여 타액선 이상, 타액선의 기능저하, 위축 또는 다른 원인에 의하여 타액분비가 감소되어 나타나는 구강 건조, 입마름 증상을 중단, 경감, 완화 또는 없애거나, 역전시키는 것을 의미한다.In the present specification, 'treatment' refers to any action that delays, stops, or reverses the progression of a disease or condition. In the present invention, salivary secretion is activated by salivary gland abnormalities, salivary gland dysfunction, atrophy, or other It means stopping, alleviating, alleviating, eliminating, or reversing the symptoms of dry mouth and dry mouth caused by reduced salivation.
본 발명에 따른 조성물은 경구 투여제, 경피투여제, 흡입투여제 등 약학적 조성물의 형태, 기능성 식품, 영양 보조제, 건강식품 및 식품 첨가제 등의 식품 조성물 형태 또는 화장료 조성물 형태로 제조되어 체내에 투여될 수 있다. 또한, 이러한 조성물은 치약, 마우스워시(mouthwash) 등과 같은 구강건강 생활제품과 개, 고양이등의 동물사료 제품에도 적용될 수 있다.The composition according to the present invention is prepared in the form of a pharmaceutical composition such as oral administration, transdermal administration, inhalation administration, food composition such as functional food, nutritional supplement, health food and food additive, or cosmetic composition and administered to the body. It can be. In addition, this composition can be applied to oral health products such as toothpaste, mouthwash, and the like, and animal feed products such as dogs and cats.
본 발명의 약학 조성물은 식물성스테롤을 약제학적으로 허용 가능한 염을 포함할 수 있다. 본 명세서에서 용어“약학적으로 허용 가능한”이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 것을 말하며, 상기 염으로는 약제학적으로 허용 가능한 유리산(free acid)에 의하여 형성된 산 부가염이 바람직하다. The pharmaceutical composition of the present invention may include a pharmaceutically acceptable salt of a plant sterol. As used herein, the term "pharmaceutically acceptable" refers to those that are physiologically acceptable and do not usually cause allergic reactions or similar reactions when administered to humans, and the salt includes a pharmaceutically acceptable free acid (free acid). acid) is preferred.
상기 식물성스테롤의 약제학적으로 허용 가능한 염은 유기산 또는 무기산을 이용하여 형성된 산 부가염일 수 있으며, 상기 유기산은 예를 들면 포름산, 아세트산, 프로피온산, 락트산, 부티르산, 이소부티르산, 트리플루오로아세트산, 말산, 말레산, 말론산, 푸마르산, 숙신산, 숙신산 모노아미드, 글루탐산, 타르타르산, 옥살산, 시트르산, 글리콜산, 글루쿠론산, 아스코르브산, 벤조산, 프탈산, 살리실산, 안트라닐산, 디클로로아세트산, 아미노옥시 아세트산, 벤젠술폰산, p-톨루엔술폰산 또는 메탄술폰산을 포함한다. 무기산은 예를 들면 염산, 브롬산, 황산, 인산, 질산, 탄산 또는 붕산을 포함한다. 산 부가염은 바람직하게는 염산염 또는 아세트산염 형태일 수 있으며, 보다 바람직하게는 염산염 형태일 수 있다.The pharmaceutically acceptable salt of the plant sterol may be an acid addition salt formed using an organic or inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, Maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxy acetic acid, benzenesulfonic acid , p-toluenesulfonic acid or methanesulfonic acid. Inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid. The acid addition salt may preferably be in the form of a hydrochloride salt or an acetate salt, more preferably in the form of a hydrochloride salt.
상기 언급된 산 부가염은 a) 식물성스테롤 및 산을 직접 혼합하거나, b) 이들 중 한 가지를 용매 또는 함수 용매 중에 용해시키고 혼합시키거나, 혹은 c) 식물성스테롤을 용매 또는 수하 용매 중의 산에 위치시키고 이들을 혼합하는 일반적인 염 제조방법으로 제조된다.The acid addition salts mentioned above are prepared by a) directly mixing a plant sterol and an acid, b) dissolving and mixing one of them in a solvent or aqueous solvent, or c) placing the plant sterol in a solvent or acid in a submerged solvent. It is prepared by a general salt production method of mixing them.
위와는 별도로 추가적으로 염이 가능한 형태는 가바염, 가바펜틴염, 프레가발린염, 니코틴산염, 아디페이트염, 헤미말론산염, 시스테인염, 아세틸시스테인염, 메티오닌염, 아르기닌염, 라이신염, 오르니틴염 또는 아스파르트산염 등이 있다. Apart from the above, additionally saltable forms include gaba salt, gabapentin salt, pregabalin salt, nicotate salt, adipate salt, hemimalonate salt, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt, or Aspartate, etc.
또한, 본 발명의 타액 분비 증강용 또는 구강건조증 예방 혹은 치료용 조성물은 약학적으로 허용 가능한 담체를 더 포함할 수 있다.In addition, the composition for enhancing salivary secretion or for preventing or treating xerostomia of the present invention may further include a pharmaceutically acceptable carrier.
약학적으로 허용되는 담체로는 예컨대, 경구 투여용 담체 또는 비경구 투여용 담체를 추가로 포함할 수 있다. 경구 투여용 담체는 락토스, 전분, 셀룰로스 유도체, 마그네슘 스테아레이트, 스테아르산 등을 포함할 수 있다. 또한 비경구 투여용 담체는 물, 적합한 오일, 식염수, 수성 글루코스 및 글리콜 등을 포함할 수 있다. 또한, 안정화제 및 보존제를 추가로 포함할 수 있다. 적합한 안정화제로는 아황산수소나트륨, 아황산나트륨 또는 아스코르브산과 같은 항산화제가 있다. 적합한 보존제로는 벤즈알코늄 클로라이드, 메틸- 또는 프로필-파라벤 및 클로로부탄올이 있다. 그 밖의 약학적으로 허용되는 담체로는 다음의 문헌에 기재되어 있는 것을 참고로 할 수 있다(Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).A pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. In addition, carriers for parenteral administration may include water, suitable oil, saline, aqueous glucose and glycol, and the like. In addition, a stabilizer and a preservative may be further included. Suitable stabilizers include antioxidants such as sodium bisulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. As other pharmaceutically acceptable carriers, reference may be made to those described in the following literature (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
본 발명의 약학 조성물은 인간을 비롯한 포유동물에 어떠한 방법으로도 투여할 수 있다. 예를 들어, 경구 또는 비경구로 투여할 수 있으며, 비경구적인 투여방법으로는 이에 제한되는 것은 아니나, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장내 투여일 수 있다.The pharmaceutical composition of the present invention can be administered to mammals including humans by any method. For example, it can be administered orally or parenterally, and parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal , intranasal, enteral, topical, sublingual or rectal administration.
본 발명의 약학 조성물은 상술한 바와 같은 투여 경로에 따라 경구 투여용 또는 비경구 투여용 제제로 제형화 할 수 있다. 제형화할 경우에는 하나 이상의 완충제(예를 들어, 식염수 또는 PBS), 항산화제, 정균제, 킬레이트화제(예를 들어, EDTA 또는 글루타치온), 충진제, 증량제, 결합제, 아쥬반트(예를 들어, 알루미늄 하이드록사이드), 현탁제, 농후제 습윤제, 붕해제 또는 계면활성제, 희석제 또는 부형제를 사용하여 조제될 수 있다.The pharmaceutical composition of the present invention may be formulated into a formulation for oral administration or parenteral administration according to the administration route as described above. When formulated, one or more buffers (eg saline or PBS), antioxidants, bacteriostats, chelating agents (eg EDTA or glutathione), fillers, bulking agents, binders, adjuvants (eg aluminum hydroxyl) side), suspending agents, thickening agents, wetting agents, disintegrating agents or surfactants, diluents or excipients.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 액제, 겔제, 시럽제, 슬러리제, 현탁액 또는 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 약학 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분(옥수수 전분, 밀 전분, 쌀 전분, 감자 전분 등 포함), 칼슘카보네이트(calcium carbonate), 수크로스(sucrose), 락토오스(lactose), 덱스트로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨 말티톨, 셀룰로즈, 메틸 셀룰로즈, 나트륨 카르복시메틸셀룰로오즈 및 하이드록시프로필메틸-셀룰로즈 또는 젤라틴 등을 섞어 조제될 수 있다. 예컨대, 활성성분을 고체 부형제와 배합한 다음 이를 분쇄하고 적합한 보조제를 첨가한 후 과립 혼합물로 가공함으로써 정제 또는 당의정제를 수득할 수 있다. Solid preparations for oral administration include tablets, pills, powders, granules, solutions, gels, syrups, slurries, suspensions or capsules, etc. These solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example , starch (including corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose , methyl cellulose, sodium carboxymethyl cellulose and hydroxypropylmethyl-cellulose or gelatin may be mixed and prepared. Tablets or dragees may be obtained, for example, by combining the active ingredient with a solid excipient which is then milled and processed into a mixture of granules after adding suitable auxiliaries.
단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물 또는 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 또는 보존제 등이 포함될 수 있다.In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, or syrups. In addition to water or liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, or preservatives may be included. .
또한, 경우에 따라 가교결합 폴리비닐피롤리돈, 한천, 알긴산 또는 나트륨 알기네이트 등을 붕해제로 첨가할 수 있으며, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.In addition, cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant, and may further include anti-agglomerating agents, lubricants, wetting agents, flavoring agents, emulsifiers, and preservatives. .
비경구적으로 투여하는 경우 본 발명의 약학 조성물은 적합한 비경구용 담체와 함께 주사제, 경피 투여제 및 비강 흡입제의 형태로 당 업계에 공지된 방법에 따라 제형화될 수 있다. 상기 주사제의 경우에는 반드시 멸균되어야 하며 박테리아 및 진균과 같은 미생물의 오염으로부터 보호되어야 한다. 주사제의 경우 적합한 담체의 예로는 이에 한정되지는 않으나, 물, 에탄올, 폴리올(예를 들어, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜 등), 이들의 혼합물 및/또는 식물유를 포함하는 용매 또는 분산매질일 수 있다. 보다 바람직하게는, 적합한 담체로는 행크스 용액, 링거 용액, 트리에탄올 아민이 함유된 PBS는 주사용 멸균수, 10% 에탄올, 40% 프로필렌 글리콜 및 5% 덱스트로즈와 같은 등장 용액 등을 사용할 수 있다. 상기 주사제를 미생물 오염으로부터 보호하기 위해서는 파라벤, 클로로부탄올, 페놀, 소르빈산, 티메로살 등과 같은 다양한 항균제 및 항진균제를 추가로 포함할 수 있다. 또한, 상기 주사제는 대부분의 경우 당 또는 나트륨 클로라이드와 같은 등장화제를 추가로 포함할 수 있다.In the case of parenteral administration, the pharmaceutical composition of the present invention may be formulated according to a method known in the art in the form of injection, transdermal administration, and nasal inhalation with a suitable parenteral carrier. In the case of the injection, it must be sterilized and must be protected from contamination by microorganisms such as bacteria and fungi. Examples of suitable carriers for injections include, but are not limited to, water, ethanol, polyols (eg, glycerol, propylene glycol, liquid polyethylene glycol, etc.), mixtures thereof, and/or solvents or dispersion media containing vegetable oils. can More preferably, suitable carriers include Hanks' solution, Ringer's solution, PBS containing triethanolamine, sterile water for injection, 10% ethanol, 40% propylene glycol, and isotonic solutions such as 5% dextrose. . In order to protect the injection from microbial contamination, various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid, and thimerosal may be further included. Also, in most cases, the injection may further include an isotonic agent such as sugar or sodium chloride.
경피 투여제의 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태가 포함된다. 상기에서 ‘경피 투여’는 약학 조성물을 국소적으로 피부에 투여하여 약학 조성물에 함유된 유효한 양의 활성성분이 피부 내로 전달되는 것을 의미한다. Transdermal preparations include ointments, creams, lotions, gels, external solutions, pastas, liniments, air rolls, and the like. In the above, 'transdermal administration' means that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin by topically administering the pharmaceutical composition to the skin.
흡입 투여제의 경우, 본 발명에 따라 사용되는 화합물은 적합한 추진제, 예를 들면, 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 또는 다른 적합한 기체를 사용하여, 가압 팩 또는 연무기로부터 에어로졸 스프레이 형태로 편리하게 전달 할 수 있다. 가압 에어로졸의 경우, 투약 단위는 계량된 양을 전달하는 밸브를 제공하여 결정할 수 있다. 예를 들면, 흡입기 또는 취입기에 사용되는 젤라틴 캡슐 및 카트리지는 화합물, 및 락토즈 또는 전분과 같은 적합한 분말 기제의 분말 혼합물을 함유하도록 제형화할 수 있다. 비경구 투여용 제형은 모든 제약 화학에 일반적으로 공지된 처방서인 문헌(Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour)에 기재되어 있다.For administration by inhalation, the compounds used according to the present invention may be administered in pressurized packs or with a suitable propellant, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be conveniently delivered in the form of an aerosol spray from a nebulizer. In the case of pressurized aerosols, dosage units may be determined by providing a valve that delivers a metered amount. For example, gelatin capsules and cartridges for use in inhalers or insufflators may be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in all pharmaceutical chemistry generally known prescriptions, Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour.
본 발명의 약학 조성물은 식물성스테롤을 유효량으로 포함 할 때 바람직한 타액 분비 증강 효과를 제공할 수 있다. 본 명세서에서, '유효량'이라 함은 음성 대조군에 비해 그 이상의 반응을 나타내는 양을 말하며 바람직하게는 타액 분비 증강에 충분한 양을 말한다. 본 발명의 약학 조성물에 식물성 스테롤이 0.01 내지 99.99% 포함될 수 있으며, 잔량은 약학적으로 허용 가능한 담체가 차지할 수 있다. 본 발명의 약학 조성물에 포함되는 식물성스테롤의 유효량은 조성물이 제품화되는 형태 등에 따라 달라질 것이다.When the pharmaceutical composition of the present invention contains an effective amount of plant sterol, it can provide a desirable saliva secretion enhancing effect. In the present specification, the term 'effective amount' refers to an amount that exhibits a higher response than that of the negative control group, and preferably refers to an amount sufficient to enhance saliva secretion. The pharmaceutical composition of the present invention may contain 0.01 to 99.99% of plant sterol, and the remaining amount may be occupied by a pharmaceutically acceptable carrier. The effective amount of the plant sterol contained in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized.
본 발명의 약학 조성물의 총 유효량은 단일 투여량(single dose)으로 환자에게 투여될 수 있으며, 다중 투여량(multiple dose)으로 장기간 투여되는 분할 치료 방법(fractionated treatment protocol)에 의해 투여될 수 있다. 본 발명의 약학 조성물은 질환의 정도에 따라 유효성분의 함량을 달리할 수 있다. 비경구 투여시는 상기 식물성스테롤을 기준으로 하루에 체중 1 kg당 바람직하게 0.01 내지 50 mg, 더 바람직하게는 0.1 내지 30 mg의 양으로 투여되도록, 그리고 경구 투여시는 β-sitosterol, stigmasterol, campesterol 및 fucosterol을 기준으로 하루에 체중 1 kg당 바람직하게 0.01 내지 100 mg, 더 바람직하게는 0.01 내지 10 mg의 양으로 투여되도록 1 내지 수회에 나누어 투여할 수 있다. 그러나 상기 식물성스테롤의 용량은 약학 조성물의 투여 경로 및 치료 횟수뿐만 아니라 환자의 연령, 체중, 건강 상태, 성별, 질환의 중증도, 식이 및 배설율 등 다양한 요인들을 고려하여 환자에 대한 유효 투여량이 결정되는 것이므로, 이러한 점을 고려할 때 당 분야의 통상적인 지식을 가진 자라면 상기 식물성스테롤을 타액 분비 증강용을 위한 특정한 용도에 따른 적절한 유효 투여량을 결정할 수 있을 것이다. 본 발명에 따른 약학 조성물은 본 발명의 효과를 보이는 한 그 제형, 투여 경로 및 투여 방법에 특별히 제한되지 아니한다.The total effective amount of the pharmaceutical composition of the present invention can be administered to the patient in a single dose, or by a fractionated treatment protocol in which multiple doses are administered over a long period of time. The pharmaceutical composition of the present invention may vary the content of the active ingredient according to the severity of the disease. In the case of parenteral administration, the plant sterol is preferably administered in an amount of 0.01 to 50 mg, more preferably 0.1 to 30 mg per kg of body weight per day based on the plant sterol, and in case of oral administration, β-sitosterol, stigmasterol, campesterol And based on fucosterol, preferably 0.01 to 100 mg, more preferably 0.01 to 10 mg per 1 kg of body weight per day, may be administered in one to several divided doses. However, the dose of the plant sterol is determined by considering various factors such as the patient's age, weight, health condition, sex, severity of disease, diet and excretion rate, as well as the route of administration of the pharmaceutical composition and the number of treatments. Therefore, considering this point, those skilled in the art will be able to determine an appropriate effective dosage according to the specific use of the plant sterol for enhancing salivary secretion. The pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route and administration method as long as it exhibits the effects of the present invention.
본 발명의 약학 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 또는 생물학적 반응조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy or biological response modifiers.
본 발명의 타액분비 증강용 또는 구강건조 또는 타액분비이상의 예방 또는 치료용 약학 조성물은 또한 식물성스테롤을 유효성분으로 포함하는 외용제의 제형으로 제공할 수 있다. 이러한 측면에서, 본 발명의 조성물은 타액분비 증강용, 또는 구강 건조증의 예방 또는 개선용 의약외품 조성물 및 상기 조성물을 포함하는 의약외품 일 수 있다.The pharmaceutical composition for enhancing salivary secretion or for preventing or treating dry mouth or abnormal salivation of the present invention may also be provided in a formulation for external use containing plant sterols as an active ingredient. In this aspect, the composition of the present invention may be a quasi-drug composition for enhancing saliva secretion or preventing or improving dry mouth, and a quasi-drug containing the composition.
상기 외용제는 피부 또는 구강 내에 직접 적용될 수 있다. 본 발명의 조성물을 외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 유화제, 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 활성제, 친유성 활성제 또는 지질 소낭 등 피부 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한, 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.The external preparation may be directly applied to the skin or oral cavity. When the composition of the present invention is used for external use, it may additionally contain a fatty substance, an organic solvent, a solubilizing agent, a thickening and gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, and water. , ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic actives, lipophilic actives or lipid vesicles, etc. It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as In addition, the components may be introduced in an amount generally used in the field of skin science.
본 발명의 조성물이 외용제로 제공될 경우, 이에 제한되는 것은 아니나, 액제, 연고, 패취, 겔, 크림 또는 분무제 등의 제형일 수 있다. 본 발명의 일 구현예에 따르면, 본 발명의 의약외품은 치약, 양치액 및 마우스 스프레이를 포함하는 구강관리 제품, 연고제, 마스크, 습포제, 첩부제 및 경피흡수제 등을 포함할 수 있다.When the composition of the present invention is provided for external use, it may be in formulations such as, but not limited to, solutions, ointments, patches, gels, creams, or sprays. According to one embodiment of the present invention, the quasi-drug of the present invention may include oral care products including toothpaste, mouthwash and mouth spray, ointments, masks, poultices, patches and transdermal absorbents.
본 발명의 일 실시예에서, 식물성스테롤을 처리하는 경우 타액선의 타액 분비작용이 증가되었는바, 상기 유효성분을 구강관리 제품에 적용하는 경우, 타액선의 타액 분비작용의 증가되어 구강건조 또는 타액분비이상에 의해 입이 마르는 증상 및 이에 의하여 발생되는 증상을 개선할 수 있다. 따라서, 상기 의약외품 조성물은 타액분비 증강용, 또는 구강건조 또는 타액분비이상의 예방 또는 개선을 위한 구강 관리용 조성물 일 수 있다.In one embodiment of the present invention, the salivary secretion of the salivary glands was increased when plant sterols were treated. When the active ingredient was applied to oral care products, the salivary secretion of the salivary glands was increased, resulting in dry mouth or abnormal salivation. It is possible to improve the symptoms of dry mouth and the symptoms caused thereby. Accordingly, the quasi-drug composition may be an oral care composition for enhancing salivary secretion or for preventing or improving dry mouth or abnormal salivation.
본 발명의 조성물을 의약외품 조성물로 사용하는 경우, 식물성스테롤을 그대로 첨가하거나 다른 의약외품 성분과 함께 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 사용목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.When the composition of the present invention is used as a quasi-drug composition, plant sterols may be added as they are or may be appropriately used in a conventional manner together with other quasi-drug ingredients. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).
본 발명의 식품 조성물은 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health food), 식품 첨가제(food additives) 및 사료 등의 모든 형태를 포함하며, 인간 또는 가축을 비롯한 동물을 취식대상으로 한다. 상기 유형의 식품 조성물은 당 업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.The food composition of the present invention includes all forms of functional food, nutritional supplements, health food, food additives, and feed, and can be used for humans or animals, including livestock. target for eating. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 일반 식품으로는 이에 한정되지 않지만 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마아말레이드 등), 어류, 육류 및 그 가공식품(예: 햄, 소시지 콘비이프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게이트, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치이즈 등), 식용식물 유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 상기 식물성스테롤을 첨가하여 제조할 수 있다. 또한, 영양보조제로는 이에 한정되지 않지만 캡슐, 타블렛, 환 등에 상기 식물성스테롤을 첨가하여 제조할 수 있다. 또한, 건강기능식품으로는 이에 한정되지 않지만 예를 들면, 식물성스테롤 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용(건강음료)할 수 있도록 액상화, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 상기 식물성스테롤을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다. 또한, 상기 식물성스테롤과 타액 분비 증강용 또는 구강건조증 예방 혹은 치료 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.Food compositions of this type can be prepared in various forms according to conventional methods known in the art. General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and their processed foods (e.g. canned fruits, bottled products, jams, marmalades, etc.), fish, meat and their processed foods (e.g. ham, sausages) Corned beef, etc.), breads and noodles (e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, taffy, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , It can be prepared by adding the plant sterol to vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.). In addition, nutritional supplements are not limited thereto, but may be prepared by adding the plant sterol to capsules, tablets, pills, etc. In addition, health functional foods are not limited thereto, but, for example, plant sterols themselves can be prepared in the form of tea, juice and drinks and liquefied, granulated, encapsulated and powdered so that they can be consumed (healthy drinks). have. In addition, in order to use the plant sterol in the form of a food additive, it may be prepared and used in the form of a powder or concentrate. In addition, it can be prepared in the form of a composition by mixing the plant sterol with a known active ingredient known to have an effect for enhancing salivary secretion or preventing or treating xerostomia.
본 발명의 식품 조성물이 건강음료 조성물로 이용되는 경우, 상기 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml 당 일반적으로 약 0.01 ∼ 0.04 g, 바람직하게는 약 0.02 ∼ 0.03 g 이다.When the food composition of the present invention is used as a health beverage composition, the health beverage composition may contain various flavoring agents or natural carbohydrates as additional components, like conventional beverages. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrins and cyclodextrins; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol. Sweeteners include natural sweeteners such as thaumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
식물성스테롤은 식품 조성물의 유효성분으로 함유될 수 있는데, 그 양은 타액 분비 증강 또는 구강건조증 예방/치료 작용을 달성하기에 유효한 양으로 특별히 한정되는 것은 아니나, 전체 조성물 총 중량에 대하여 0.01 내지 100 중량 %인 것이 바람직하다. 본 발명의 식품 조성물은 식물성스테롤과 함께 타액 분비 증강 조성물에 효과가 있는 것으로 알려진 다른 활성 성분과 함께 혼합하여 제조될 수 있다.Plant sterols may be contained as an active ingredient in a food composition, the amount of which is not particularly limited to an amount effective to achieve salivary secretion enhancement or xerostomia prevention/treatment, but 0.01 to 100% by weight based on the total weight of the total composition. It is desirable to be The food composition of the present invention can be prepared by mixing plant sterols with other active ingredients known to be effective in saliva secretion enhancing compositions.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, It may contain glycerin, alcohol or a carbonating agent and the like. In addition, the health food of the present invention may contain fruit flesh for producing natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
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본 발명의 일실시예에서는 베타-시토스테롤, 스티그마스테롤, 캠페스테롤, 및 푸코스테롤의 타액 분비 증강 효과를 확인하기 위하여, 인간 침샘 세포에 상기 식물성스테롤을 각각 처리한 결과, 처리 전보다 처리 후에 타액 분비 기전의 주요 인자인 Ca2+가 현저히 증가함을 확인하였다.In one embodiment of the present invention, in order to confirm the effect of enhancing salivary secretion of beta-sitosterol, stigmasterol, campesterol, and fucosterol, human salivary gland cells were treated with the plant sterols, respectively. It was confirmed that Ca2+, a major factor of , was remarkably increased.
본 발명의 다른 일실시예에서는 베타-시토스테롤, 스티그마스테롤, 캠페스테롤, 및 푸코스테롤의 타액 분비 증강 효과를 확인하기 위하여, 인간 침샘 세포에 상기 식물성스테롤을 각각 처리한 결과, 처리 전보다 처리 후에 타액 분비시 발현되는 주요 단백질인 AQP5의 mRNA 발현량이 증가한 것을 확인하였는 바, 본 발명의 식물성스테롤들의 타액 분비 증강 효과가 우수함을 확인하였다.In another embodiment of the present invention, in order to confirm the effect of enhancing salivary secretion of beta-sitosterol, stigmasterol, campesterol, and fucosterol, human salivary gland cells were treated with the plant sterols, respectively. As it was confirmed that the mRNA expression level of AQP5, a major protein expressed at the time of treatment, increased, it was confirmed that the salivary secretion enhancing effect of the plant sterols of the present invention was excellent.
본 발명의 식물성스테롤은 타액 분비 기전의 주요 인자인 세포 내 칼슘 이온의 농도를 증가시켜 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료에 우수한 효과를 보인다. 따라서 본 발명은 천연물이므로 부작용 없이 안전하게 사용될 수 있으며, 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료에 탁월한 효과를 보이는 조성물을 제공할 수 있다.The plant sterols of the present invention increase the concentration of intracellular calcium ions, which is a major factor in the secretion mechanism of saliva, and show excellent effects in enhancing salivary secretion or preventing, improving, or treating xerostomia. Therefore, since the present invention is a natural product, it can be safely used without side effects, and can provide a composition that exhibits excellent effects in preventing, improving, or treating dry mouth or enhancing salivary secretion.
도 1은 인간 침샘 세포(Human Salivary Gland, HSG)에서 β-sitosterol 처리에 따른 세포 내 Ca2+을 측정한 그래프이다.
도 2는 인간 침샘 세포(HSG)에서 stigmasterol 처리에 따른 세포 내 Ca2+을 측정한 그래프이다.
도 3은 인간 침샘 세포(HSG)에서 campesterol 처리에 따른 세포 내 Ca2+을 측정한 그래프이다.
도 4는 인간 침샘 세포(HSG)에서 fucosterol 처리에 따른 세포 내 Ca2+을 측정한 그래프이다.
도 5는 인간 침샘 세포(HSG)에서 식물성스테롤 (1. β-Sitosterol, 2. Campesterol, 3. Fucosterol, 4. Stigmasterol) 처리에 따른 AQP5의 mRNA 발현을 RT-PCR로 확인한 결과이다.1 is a graph measuring intracellular Ca 2+ according to β-sitosterol treatment in human salivary gland cells (Human Salivary Gland, HSG).
Figure 2 is a graph measuring intracellular Ca 2+ according to stigmasterol treatment in human salivary gland cells (HSG).
3 is a graph measuring intracellular Ca 2+ according to campesterol treatment in human salivary gland cells (HSG).
Figure 4 is a graph measuring intracellular Ca 2+ according to fucosterol treatment in human salivary gland cells (HSG).
Figure 5 is a result of confirming the mRNA expression of AQP5 according to the plant sterol (1. β-Sitosterol, 2. Campesterol, 3. Fucosterol, 4. Stigmasterol) treatment in human salivary gland cells (HSG) by RT-PCR.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.However, the following examples are only to illustrate the present invention, and the content of the present invention is not limited to the following examples.
<실험 재료><Experiment materials>
β-sitosterol (CAS Number: 83-46-5, Empirical Formula: C29H50O, Molecular Weight:: 414.72 g/mol), stigmasterol (CAS Number: 83-48-7, Empirical Formula: C29H48O, Molecular Weight: 412.70 g/mol), campesterol (CAS Number: 474-62-4, Empirical Formula: C28H48O, Molecular Weight: 400.69 g/mol) 및 fucosterol (CAS Number: 17605-67-3, Empirical Formula: C29H48O, Molecular Weight: 412.69 g/mol) 은 Sigma-Aldrich (St.Louis, MO, USA)에서 구입하였다.β-sitosterol (CAS Number: 83-46-5, Empirical Formula: C 29 H 50 O, Molecular Weight:: 414.72 g/mol), stigmasterol (CAS Number: 83-48-7, Empirical Formula: C 29 H 48 O, Molecular Weight: 412.70 g/mol), campesterol (CAS Number: 474-62-4, Empirical Formula: C 28 H 48 O, Molecular Weight: 400.69 g/mol) and fucosterol (CAS Number: 17605-67-3 , Empirical Formula: C 29 H 48 O, Molecular Weight: 412.69 g/mol) was purchased from Sigma-Aldrich (St.Louis, MO, USA).
<실시예 1><Example 1>
β-Sitosterol의 타액 분비 증강 효능검증Verification of saliva secretion enhancing efficacy of β-Sitosterol
세포 내 Ca2+측정을 통한 β-sitosterol의 타액 분비 증강 효능검증을 실시하였다. 인간 침샘 세포(HSG)를 두 개의100 mm dish에 10 %의 fetal bovine serum (FBS, Hyclone, Logan, UT, USA)이 함유된 Dulbecco's Modified Eagle's Medium (DMEM, Hyclone)배지를 이용하여 배양하였다. 100 mm dish에 세포밀도가 95%가 되었을 때, 세포를 수획하여 큐벳(cuvette)에 담았다. Ca2+ indicator인 Fura-2AM (Thermo Fisher Scientific Inc., Waltham, MA, USA)에 sulfinpyrazone (Thermo Fisher Scientific) 5 μL을 넣고 색이 변하는 것을 확인한 후 세포가 담긴 큐벳(cuvette)에 넣었다. Spectrofluorophotometer RF-5301 (Shimadzu, Kyoto, Japan)에 큐벳(cuvette)을 넣고 stirrer를 작동시켜 1시간 동안 loading하였다. 1시간이 지나면 큐벳(cuvette)내에 있는 세포를 1.5 mL tube에 옮겨 담고 DMEM (Hyclone)으로 washing하여 세포 밖 media에 있는 Ca2+을 제거하였다. Locke's solution 900 μL와 DMEM (Hyclone)으로 suspension 된 세포 100 μL를 큐벳(cuvette)에 넣고 100초간 기다린 후, β-sitosterol을 50 μM의 농도로 처리하였다. Fura-2AM (Thermo Fisher Scientific)의 자체 흡수 파장대인 380 nm와 Ca2+과 결합한 fura-2AM (Thermo Fisher Scientific)의 흡수 파장대인 340 nm에서 두 물질의 흡광도를 Spectrofluorophotometer RF-5301 ( Shimadzu)으로 측정하였고, 결과적으로 세포 내 Ca2+의 증가율을 F340nm/F380nm으로 나타내었다. 하기 수학식 1에 따라 β-sitosterol을 처리하기 전 대비 처리 후 Ca2+증가율을 계산하였다.The saliva secretion enhancing efficacy of β-sitosterol was verified by measuring intracellular Ca 2+ . Human salivary gland cells (HSG) were cultured in two 100 mm dishes using Dulbecco's Modified Eagle's Medium (DMEM, Hyclone) medium containing 10% fetal bovine serum (FBS, Hyclone, Logan, UT, USA). When the cell density in the 100 mm dish reached 95%, the cells were harvested and placed in a cuvette. After adding 5 μL of sulfinpyrazone (Thermo Fisher Scientific) to Fura-2AM (Thermo Fisher Scientific Inc., Waltham, MA, USA), which is a Ca 2+ indicator, and confirming that the color changes, it was placed in a cuvette containing cells. A cuvette was put into a spectrofluorophotometer RF-5301 (Shimadzu, Kyoto, Japan), and loading was performed for 1 hour by operating a stirrer. After 1 hour, the cells in the cuvette were transferred to a 1.5 mL tube and washed with DMEM (Hyclone) to remove Ca 2+ in the extracellular media. 900 μL of Locke's solution and 100 μL of cells suspended in DMEM (Hyclone) were placed in a cuvette, waited for 100 seconds, and then treated with β-sitosterol at a concentration of 50 μM. Measure the absorbance of the two materials at 380 nm, the self-absorption wavelength range of Fura-2AM (Thermo Fisher Scientific) and 340 nm, the absorption wavelength range of fura-2AM (Thermo Fisher Scientific) combined with Ca 2+ , using a Spectrofluorophotometer RF-5301 (Shimadzu) As a result, the increase rate of intracellular Ca 2+ was expressed as F340nm/F380nm. According to
그 결과, 도 1에 나타낸 바와 같이 β-sitosterol을 처리하기 전 F340/F380 ratio의 최저값은 2.273이였고, β-sitosterol 처리 후 F340/F380 ratio의 최고값은 3.474였다. 3.474/2.273 × 100 = 152.8 % 이므로, β-sitosterol에 의해 세포 내 Ca2+레벨이 약 53 % 증가한 것을 알 수 있었다. 이는 본 발명의 β-sitosterol이 타액 분비 기전의 주요 인자인 Ca2+ 을 증가시켜 타액 분비 증강 효능이 우수하다는 것을 의미한다. As a result, as shown in Figure 1, the lowest value of F340 / F380 ratio before treatment with β-sitosterol was 2.273, and the highest value of F340 / F380 ratio after treatment with β-sitosterol was 3.474. Since 3.474/2.273 × 100 = 152.8%, it was found that the intracellular Ca 2+ level was increased by about 53% by β-sitosterol. This means that the β-sitosterol of the present invention increases Ca2+, which is a major factor in the salivary secretion mechanism, and thus has excellent salivary secretion enhancing efficacy.
<실시예 2><Example 2>
Stigmasterol 의 타액 분비 증강 효능검증Verification of salivary secretion enhancing efficacy of Stigmasterol
세포 내 Ca2+측정을 통한 stigmasterol의 타액 분비 증강 효능검증을 실시하였다. 상기 실시예 1과 동일한 방법으로 인간 침샘 세포(HSG)를 배양한 후 stigmasterol을 50 μM의 농도로 처리하여 세포 내 Ca2+의 증가율을 F340nm/F380nm으로 나타내었다. 상기 수학식 1에 따라 stigmasterol을 처리하기 전 대비 처리 후 Ca2+증가율을 계산하였다.The saliva secretion enhancing efficacy of stigmasterol was verified through intracellular Ca 2+ measurement. After culturing human salivary gland cells (HSG) in the same manner as in Example 1, stigmasterol was treated at a concentration of 50 μM, and the increase rate of intracellular Ca 2+ was expressed as F340nm/F380nm. According to
그 결과, 도 2에 나타낸 바와 같이 stigmasterol을 처리하기 전 F340/F380 ratio의 최저값은 2.065이였고, stigmasterol 처리 후 F340/F380 ratio의 최고값은 3.129였다. 3.129/2.065 ×100 = 151.5 % 이므로, stigmasterol에 의해 세포 내 Ca2+레벨이 약 52 % 증가한 것을 알 수 있었다. 이는 본 발명의 stigmasterol이 타액 분비 기전의 주요 인자인 Ca2+을 증가시켜 타액 분비 증강 효능이 우수하다는 것을 의미한다.As a result, as shown in FIG. 2, the lowest F340/F380 ratio before treatment with stigmasterol was 2.065, and the highest value of F340/F380 ratio after treatment with stigmasterol was 3.129. Since 3.129/2.065 × 100 = 151.5%, it was found that stigmasterol increased the intracellular Ca 2+ level by about 52%. This means that the stigmasterol of the present invention increases Ca 2+ , which is a major factor in the salivary secretion mechanism, and thus has excellent salivary secretion enhancing efficacy.
<실시예3><Example 3>
Campesterol의 타액 분비 증강 효능검증Campesterol's salivary secretion enhancing efficacy verification
세포 내 Ca2+측정을 통한 campesterol의 타액 분비 증강 효능검증을 실시하였다. 상기 실시예 1과 동일한 방법으로 인간 침샘 세포(HSG)를 배양한 후 campesterol을 50 μM의 농도로 처리하여 세포 내 Ca2+의 증가율을 F340nm/F380nm으로 나타내었다. 상기 수학식 1에 따라 campesterol을 처리하기 전 대비 처리 후 Ca2+증가율을 계산하였다.The salivary secretion enhancing efficacy of campesterol was verified by measuring intracellular Ca 2+ . After culturing human salivary gland cells (HSG) in the same manner as in Example 1, campesterol was treated at a concentration of 50 μM, and the increase rate of intracellular Ca 2+ was expressed as F340nm/F380nm. According to
그 결과, 도 3에 나타낸 바와 같이 campesterol을 처리하기 전 F340/F380 ratio의 최저값은 2.337이였고, campesterol 처리 후 F340/F380 ratio의 최고값은 3.328이였다. 3.328/2.337 ×100 = 142.4 % 이므로, campesterol에 의해 세포 내 Ca2+레벨이 약 42 % 증가한 것을 알 수 있었다. 이는 본 발명의 campesterol이 타액 분비 기전의 주요 인자인 Ca2+ 을 증가시켜 타액 분비 증강 효능이 우수하다는 것을 의미한다.As a result, as shown in FIG. 3, the lowest F340/F380 ratio before treatment with campesterol was 2.337, and the highest value of F340/F380 ratio after treatment with campesterol was 3.328. Since 3.328/2.337 × 100 = 142.4%, it was found that the intracellular Ca 2+ level was increased by about 42% by campesterol. This means that the campesterol of the present invention increases Ca 2+ , which is a major factor in the salivary secretion mechanism, and thus has excellent salivary secretion enhancing efficacy.
<실시예 4><Example 4>
Fucosterol의 타액 분비 증강 효능검증Verification of salivary secretion enhancing efficacy of fucosterol
세포 내 Ca2+측정을 통한 fucosterol의 타액 분비 증강 효능검증을 실시하였다. 상기 실시예 1과 동일한 방법으로 인간 침샘 세포(HSG)를 배양한 후 fucosterol을 20 μM의 농도로 처리하여 세포 내 Ca2+의 증가율을 F340nm/F380nm으로 나타내었다. 상기 수학식 1에 따라 fucosterol을 처리하기 전 대비 처리 후 Ca2+증가율을 계산하였다.The salivary secretion enhancing efficacy of fucosterol was verified by measuring intracellular Ca 2+ . After culturing human salivary gland cells (HSG) in the same manner as in Example 1, fucosterol was treated at a concentration of 20 μM, and the increase rate of intracellular Ca 2+ was expressed as F340nm/F380nm. According to
그 결과, 도 4에 나타낸 바와 같이 fucosterol을 처리하기 전 F340/F380 ratio의 최저값은 2.22이였고, fucosterol 처리 후 F340/F380 ratio의 최고값은 3.837였다. 3.837/2.22 ×100 = 172.8 % 이므로, fucosterol에 의해 세포 내 Ca2+레벨이 약 73 % 증가한 것을 알 수 있었다. 이는 본 발명의 fucosterol이 타액 분비 기전의 주요 인자인 Ca2+ 을 증가시켜 타액 분비 증강 효능이 우수하다는 것을 의미한다.As a result, as shown in FIG. 4, the lowest value of the F340/F380 ratio before treatment with fucosterol was 2.22, and the highest value of F340/F380 ratio after treatment with fucosterol was 3.837. Since 3.837/2.22 × 100 = 172.8%, it was found that the intracellular Ca 2+ level was increased by about 73% by fucosterol. This means that the fucosterol of the present invention increases Ca 2+ , which is a major factor in the salivary secretion mechanism, and thus has excellent salivary secretion enhancing efficacy.
<실시예 5><Example 5>
RT-PCR을 통한 β-sitosterol, stigmasterol, campesterol, fucosterol의 타액 분비 증강 효능검증Verification of saliva secretion enhancement efficacy of β-sitosterol, stigmasterol, campesterol, and fucosterol through RT-PCR
인간 침샘 세포(HSG)를 6-웰 평판배양기(6-well microtiter plate)에 10 %의 Fetal bovine serum (FBS, Hyclone, Logan, UT, USA)가 함유된 Dulbecco's Modified Eagle's Medium (DMEM, Hyclone)을 이용하여 5 × 10?세포/웰이 되도록 넣었다. 24시간 후, 웰에 있는 배지를 제거하고 10 %의 FBS (Hyclone)가 함유된 DMEM (Hyclone)에 β-sitosterol, campesterol, stigmasterol을 각각 50 μM, fucosterol을 20 μM로 세포에 20분간 처리하였다. 그 후 타액 분비 시 발현되는 주요 단백질인 AQP5의 mRNA 발현량을 알아보기 위해 RT-PCR을 수행하였다. 세포로부터 TRIzol시약(Takara, Tokyo, Japan)을 사용하여 총 RNA를 분리하였다. 분리한 총 RNA는 나노드랍(NanoDrop 1000, Thermo Fisher Scientific, Waltham, MA, USA)을 이용하여 정량하였다. 정량된 16 μL의 RNA를 Reverse Transcriptase Premix (ELPIS-Biotech, Daejeon, Korea)와 PCR 기계(Gene Amp PCR System 2700, Applied Biosystems, Waltham, MA, USA)를 이용하여 42°C 55분, 70°C 15분의 조건에서 cDNA로 합성하였다. 16 μL의 생성된 cDNA 중 4 μL의 cDNA, 하기의 특정 프라이머(Bioneer, Daejeon, Korea) 그리고 HiPi PCR Premix (ELPIS-Biotech)로 95°C에서 30초, 53°C에서 1분, 72°C에서 1분을 23번 반복하여 PCR을 수행하였다.Human salivary gland cells (HSG) were cultured in Dulbecco's Modified Eagle's Medium (DMEM, Hyclone) containing 10% Fetal bovine serum (FBS, Hyclone, Logan, UT, USA) in a 6-well microtiter plate. 5 × 10? cells/well were put in using. After 24 hours, the medium in the well was removed, and cells were treated with 50 μM each of β-sitosterol, campesterol, and 20 μM fucosterol in DMEM (Hyclone) containing 10% FBS (Hyclone) for 20 minutes. Then, RT-PCR was performed to determine the mRNA expression level of AQP5, a major protein expressed during salivary secretion. Total RNA was isolated from cells using TRIzol reagent (Takara, Tokyo, Japan). Isolated total RNA was quantified using a nanodrop (NanoDrop 1000, Thermo Fisher Scientific, Waltham, MA, USA). Quantified 16 μL of RNA was prepared using Reverse Transcriptase Premix (ELPIS-Biotech, Daejeon, Korea) and a PCR machine (Gene Amp PCR System 2700, Applied Biosystems, Waltham, MA, USA) at 42°C for 55 minutes at 70°C. It was synthesized into cDNA under the condition of 15 minutes. 4 μL of cDNA out of 16 μL of generated cDNA, the following specific primers (Bioneer, Daejeon, Korea) and HiPi PCR Premix (ELPIS-Biotech) at 95 °C for 30 seconds, 53 °C for 1 minute, 72 °C PCR was performed by repeating 1 minute 23 times.
AQP5:AQP5:
Forward primer : 5'-AAGACCATGGAGCTGACCAC-3' (서열번호 1)Forward primer: 5'-AAGACCATGGAGCTGACCAC-3' (SEQ ID NO: 1)
Reverse primer : 5‘-CCCTCTCTAACTGTGCAGCC-3' (서열번호 2)Reverse primer: 5‘-CCCTCTCTAACTGTGCAGCC-3’ (SEQ ID NO: 2)
GAPDH:GAPDH:
Forward primer : 5‘-CTCCTGTTCGACAGTCAGCC-3’ (서열번호 3)Forward primer: 5'-CTCCTGTTCGACAGTCAGCC-3' (SEQ ID NO: 3)
Reverse primer : 5‘-TCGCCCCACTTGATTTTGGA-3’ (서열번호 4)Reverse primer: 5'-TCGCCCCACTTGATTTTGGA-3' (SEQ ID NO: 4)
그 결과, 도 5에 나타낸 바와 같이 β-sitosterol, campesterol, stigmasterol, 그리고 fucosterol 처리에 의해 인간 침샘 세포에서 AQP5 mRNA 발현량이 증가한 것을 확인할 수 있었다. 이는 본 발명의 상기 식물성스테롤이 타액 분비 증강 효능이 우수하다는 것을 의미한다.As a result, as shown in FIG. 5, it was confirmed that the AQP5 mRNA expression level increased in human salivary gland cells by treatment with β-sitosterol, campesterol, stigmasterol, and fucosterol. This means that the plant sterols of the present invention are excellent in enhancing saliva secretion.
이하, 본 발명에 따른 상기 실시예 1내지 5의 식물성스테롤을 유효성분으로 함유하는 의약품 및 식품의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다. 상기 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료 효과가 우수한 식물성스테롤을 가지고 하기와 같은 조성성분 및 조성비에 따라 제조예 1 내지 2의 의약품 및 식품 조성물을 통상적인 방법에 따라서 제조하였다.Hereinafter, manufacturing examples of pharmaceuticals and foods containing the plant sterols of Examples 1 to 5 according to the present invention as an active ingredient will be described, but the present invention is not intended to limit them, but only to be specifically described. The pharmaceutical and food compositions of Preparation Examples 1 and 2 were prepared according to the conventional method according to the following compositional components and composition ratios with plant sterols having excellent salivary secretion enhancement or prevention, improvement or treatment effect of xerostomia.
[제조예 1] 의약품[Production Example 1] Pharmaceuticals
<1-1> 산제<1-1> Powder
상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 50 mg, 결정셀룰로오즈 2 g을 혼합한 후 통상의 산제 제조방법에 따라서 기밀포에 충진하여 산제를 제조하였다.Powders were prepared by mixing 50 mg of β-sitosterol, stigmasterol, campesterol and/or fucosterol and 2 g of crystalline cellulose of Examples 1 to 5, and filling them into airtight bags according to a conventional powder preparation method.
<1-2> 정제<1-2> Refining
상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 50 mg, 결정셀룰로오즈 400 mg, 스테아린산 마그네슘 5 mg을 혼합한 후 통상의 정제 제조방법에 따라서 타정하여 정제를 제조하였다.Tablets were prepared by mixing 50 mg of β-sitosterol, stigmasterol, campesterol and/or fucosterol, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate from Examples 1 to 5, and then tableting according to a conventional tablet manufacturing method.
<1-3> 캡슐제<1-3> Capsules
상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 30 mg, 유청단백질 100 mg, 결정셀룰로오즈 400 mg, 스테아린산 마그네슘 6 mg을 혼합한 후 통상의 캡슐제 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing 30 mg of β-sitosterol, stigmasterol, campesterol and/or fucosterol, 100 mg of whey protein, 400 mg of crystalline cellulose, and 6 mg of magnesium stearate from Examples 1 to 5, form a gelatin capsule according to the conventional capsule preparation method. Capsules were prepared by filling.
<1-4> 주사제<1-4> Injectables
통상의 주사제 제조방법에 따라 활성성분을 주사용 증류수에 용해하고 pH를 약 7.5로 조절한 다음 상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 100 mg, 주사용 증류수, pH 조절제를 혼합하여 2 ml 용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.According to the conventional method for preparing injections, the active ingredient was dissolved in distilled water for injection, the pH was adjusted to about 7.5, and 100 mg of β-sitosterol, stigmasterol, campesterol and / or fucosterol of Examples 1 to 5, distilled water for injection, pH An injection was prepared by mixing the regulator and filling a 2 ml ampoule and sterilizing it.
[제조예 2] 식품[Production Example 2] Food
<2-1> 건강식품의 제조<2-1> Manufacture of health food
상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 1000 mg, 비타민 A 아세테이트 70 ug, 비타민 E 1.0 mg, 비타민 B1 0.13 mg, 비타민 B2 0.15 mg, 비타민 B6 0.5 mg, 비타민 B12 0.2 ug, 비타민 C 10 mg, 비오틴 10 ug, 니코틴산아미드 1.7 mg, 엽산 50 ug, 판토텐산 칼슘 0.5 mg, 황산제1철 1.75 mg, 산화아연 0.82 mg, 탄산마그네슘 25.3 mg, 제1인산칼륨 15 mg, 제2인산칼슘 55 mg, 구연산칼륨 90 mg, 탄산칼슘 100 mg, 염화마그네슘 24.8 mg를 혼합하여 제조할 수 있으며, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.1000 mg of β-sitosterol, stigmasterol, campesterol and/or fucosterol of Examples 1 to 5, 70 ug of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of vitamin B1, 0.15 mg of vitamin B2, 0.5 mg of vitamin B6, and 0.2 of vitamin B12 ug, vitamin C 10 mg, biotin 10 ug, nicotinamide 1.7 mg,
<2-2> 건강음료의 제조<2-2> Manufacture of health drinks
상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 1000 mg, 구연산 1000 mg, 올리고당 100 g, 매실농축액 2 g, 타우린 1 g에 정제수를 가하여 전체 900 ml 통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 건강음료 조성물 제조에 사용할 수 있다.1000 mg of β-sitosterol, stigmasterol, campesterol and/or fucosterol, 1000 mg of citric acid, 100 g of oligosaccharide, 2 g of plum concentrate, and 1 g of taurine in Examples 1 to 5 were added with purified water to make a total of 900 ml of normal health beverage manufacturing method After mixing the above ingredients according to, and then stirring and heating at 85 for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and then refrigerated, and then used for preparing a health drink composition. .
<2-3> 츄잉껌<2-3> Chewing gum
껌 베이스 20 중량%, 설탕 76.9 중량%, 향료 1 중량% 및 물 2 중량% 와 상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 0.1 중량%를 배합하여 통상의 방법으로 츄잉껌을 제조하였다.20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of flavoring agent, 2% by weight of water, and 0.1% by weight of β-sitosterol, stigmasterol, campesterol and/or fucosterol of Examples 1 to 5 were blended and chewing gum was prepared in a conventional manner. was manufactured.
<2-4> 캔디<2-4> Candy
설탕 60 중량%, 물엿 39.8 중량% 및 향료 0.1 중량%와 상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 0.1 중량%를 배합하여 통상의 방법으로 캔디를 제조하였다.60% by weight of sugar, 39.8% by weight of starch syrup, 0.1% by weight of flavoring, and 0.1% by weight of β-sitosterol, stigmasterol, campesterol and / or fucosterol of Examples 1 to 5 were mixed to prepare candy in a conventional manner.
<2-5> 비스켓<2-5> Biscuit
박력 1급 25.59 중량%, 중력 1급 22.22 중량%, 정백당 4.80 중량%, 식염 0.73 중량%, 포도당 0.78 중량%, 팜쇼트닝 11.78 중량%, 암모늄 1.54 중량%, 중조 0.17 중량%, 중아황산나트륨 0.16 중량%, 쌀가루 1.45 중량%, 비타민 B 0.0001 중량%, 밀크향 0.04 중량%, 물 20.6998 중량%, 전지분유 1.16 중량%, 대용분유 0.29 중량%, 제1인산칼슘 0.03 중량%, 살포염 0.29 중량% 및 분무유 7.27 중량%와 상기 실시예 1내지 5의 β-sitosterol, stigmasterol, campesterol 및/또는 fucosterol 중량%를 배합하여 통상의 방법으로 비스켓을 제조하였다.Strength 1st grade 25.59% by weight, gravity 1st grade 22.22% by weight, white sugar 4.80% by weight, table salt 0.73% by weight, glucose 0.78% by weight, palm shortening 11.78% by weight, ammonium 1.54% by weight, sodium bicarbonate 0.17% by weight, sodium bisulfite 0.16% by weight , Rice flour 1.45% by weight, vitamin B 0.0001% by weight, milk flavor 0.04% by weight, water 20.6998% by weight, whole milk powder 1.16% by weight, substitute powdered milk 0.29% by weight, monobasic calcium phosphate 0.03% by weight, dusting salt 0.29% by weight and spray Biscuits were prepared in a conventional manner by combining 7.27% by weight of oil with β-sitosterol, stigmasterol, campesterol and/or fucosterol in Examples 1 to 5 by weight.
이상 살펴본 바와 같이, 본 발명의 식물성스테롤은 타액 분비 기전의 주요 인자인 세포 내 칼슘 이온의 농도를 증가시켜 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료에 우수한 효과를 보인다. 따라서 본 발명은 천연물이므로 부작용 없이 안전하게 사용될 수 있으며, 타액 분비 증강 또는 구강건조증 예방, 개선 혹은 치료에 탁월한 효과를 보이는 조성물을 제공할 수 있으므로 산업상 이용가능성이 높다.As described above, the plant sterols of the present invention increase the concentration of intracellular calcium ions, which is a major factor in the salivary secretion mechanism, and show excellent effects in enhancing salivary secretion or preventing, improving, or treating xerostomia. Therefore, since the present invention is a natural product, it can be safely used without side effects and has high industrial applicability because it can provide a composition that exhibits excellent effects in preventing, improving, or treating salivary secretion or dry mouth.
<110> AAT Costech Co., Ltd.
<120> Composition for increasing salivary secretion; or prevention or
treatment of xerostomia comprising phytosterols
<130> NP17-0121
<160> 4
<170> KoPatentIn 3.0
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<223> Aquasporin5 primer Forward
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<213> Artificial Sequence
<220>
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ccctctctaa ctgtgcagcc 20
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<211> 20
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<220>
<223> GAPDH primer Forward
<400> 3
ctcctgttcg acagtcagcc 20
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<211> 20
<212> RNA
<213> Artificial Sequence
<220>
<223> GAPDH primer Reverse
<400> 4
tcgccccact tgattttgga 20
<110> AAT Costech Co., Ltd.
<120> Composition for increasing salivary secretion; or prevention or
treatment of xerostomia comprising phytosterols
<130> NP17-0121
<160> 4
<170> KoPatentIn 3.0
<210> 1
<211> 20
<212> RNA
<213> artificial sequence
<220>
<223> Aquasporin5 primer Forward
<400> 1
aagaccatgg agctgaccac 20
<210> 2
<211> 20
<212> RNA
<213> artificial sequence
<220>
<223> Aquasporin5 primer Reverse
<400> 2
ccctctctaa ctgtgcagcc 20
<210> 3
<211> 20
<212> RNA
<213> artificial sequence
<220>
<223> GAPDH primer Forward
<400> 3
ctcctgttcg acagtcagcc 20
<210> 4
<211> 20
<212> RNA
<213> artificial sequence
<220>
<223> GAPDH primer Reverse
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Claims (10)
A pharmaceutical composition for enhancing saliva secretion comprising plant sterols (pnytosterols) as an active ingredient.
The composition according to claim 1, wherein the plant sterol is at least one selected from β-sitosterol, stigmasterol, campesterol, and fucosterol.
A food composition for enhancing saliva secretion comprising plant sterols (pnytosterols) as an active ingredient.
A pharmaceutical composition for preventing or treating xerostomia, comprising plant sterols (pnytosterols) as an active ingredient.
A pharmaceutical composition for preventing or improving dry mouth comprising plant sterols (pnytosterols) as an active ingredient.
For enhancing saliva secretion containing plant sterols as an active ingredient; or for preventing or improving dry mouth; Quasi-drug composition.
For enhancing saliva secretion containing plant sterols as an active ingredient; or for preventing or improving dry mouth; Quasi-drugs.
The quasi-drug composition according to claim 7, wherein the plant sterol is at least one selected from β-sitosterol, stigmasterol, campesterol, and fucosterol.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4963346A (en) | 1988-05-31 | 1990-10-16 | Amer & Company, Inc. | Method and composition for treatment or prevention of dental plaque calculus and gingivitis |
WO2003063605A1 (en) | 2002-02-01 | 2003-08-07 | Eugene Science Inc. | Chewing gum composition containing plant sterol for decrease of flood cholesterol levels and prevention of periodontal disease |
KR100817599B1 (en) | 2006-12-22 | 2008-03-31 | 재단법인 전주생물소재연구소 | Toothpaste composition for preventing dental caries |
US20090053309A1 (en) | 2007-08-24 | 2009-02-26 | Axiomedic Ltd., Gibraltar | Adhesive compositions for the treatment of xerostomia |
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KR20160084904A (en) * | 2015-01-06 | 2016-07-15 | (주) 바이오에스텍 | Composition for sanitation promotion of oral cavity comprising natural medicinal ingredient extract as effective component |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4963346A (en) | 1988-05-31 | 1990-10-16 | Amer & Company, Inc. | Method and composition for treatment or prevention of dental plaque calculus and gingivitis |
WO2003063605A1 (en) | 2002-02-01 | 2003-08-07 | Eugene Science Inc. | Chewing gum composition containing plant sterol for decrease of flood cholesterol levels and prevention of periodontal disease |
KR100817599B1 (en) | 2006-12-22 | 2008-03-31 | 재단법인 전주생물소재연구소 | Toothpaste composition for preventing dental caries |
US20090053309A1 (en) | 2007-08-24 | 2009-02-26 | Axiomedic Ltd., Gibraltar | Adhesive compositions for the treatment of xerostomia |
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