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WO2006001664A1 - Composition destinee a prevenir ou traiter des maladies cerebrales degeneratives aigues ou chroniques et contenant un extrait de selaginella tamariscina spring - Google Patents

Composition destinee a prevenir ou traiter des maladies cerebrales degeneratives aigues ou chroniques et contenant un extrait de selaginella tamariscina spring Download PDF

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Publication number
WO2006001664A1
WO2006001664A1 PCT/KR2005/001985 KR2005001985W WO2006001664A1 WO 2006001664 A1 WO2006001664 A1 WO 2006001664A1 KR 2005001985 W KR2005001985 W KR 2005001985W WO 2006001664 A1 WO2006001664 A1 WO 2006001664A1
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WO
WIPO (PCT)
Prior art keywords
composition
extract
selaginella tamariscina
tamariscina spring
degenerative brain
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2005/001985
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English (en)
Inventor
Byung-Hee Han
Sam-Sik Kang
Kun-Ho Son
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Seoul National University Industry Foundation
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Seoul National University Industry Foundation
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Filing date
Publication date
Application filed by Seoul National University Industry Foundation filed Critical Seoul National University Industry Foundation
Publication of WO2006001664A1 publication Critical patent/WO2006001664A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/898—Orchidaceae (Orchid family)
    • 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
    • A61K36/10—Bryophyta (mosses)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates to a composition for preventing or treating acute or chronic degenerative brain diseases including an extract of Selaginella tamariscina Spring as an effective ingredient.
  • Acute degenerative brain diseases such as ischemic stroke, together with chronic degenerative brain diseases such as dementia, are disorders causing loss of brain function due to continuous destruction of cerebral nerve cells.
  • Degenerative brain diseases exhibit various symptoms such as memory disorder, language disorder, space- time perception disability, judgment disability, personality and emotional disorder according to the degree of brain damage and an affected site, and cause permanent loss of brain function.
  • In Korea about 10% and 1% of people with the age of 65 or more suffer from senile dementia and Parkinson's disease, respectively. Ischemic stroke is the second leading cause of death after cancer.
  • degenerative brain diseases are adult diseases that the frequency of occurrence rapidly increases in aged persons with 50 or more of age.
  • degenerative brain diseases are major diseases that represent a serious social and economical burden and lower the life quality of aged persons.
  • a recent trend is toward elevation of de ⁇ generative brain disease patients due to an increase in aged population with increasing average lifespan.
  • flavonoids are naturally occurring multivalent phenol compounds present in fruits, vegetables, seeds, etc.
  • flavonoid derivatives categorized, according to chemical structure, into flavonols, flavones, and isoflavones, are known, and their biological and pharmacological activities have been studied.
  • Korean Patent Nos. 139,179 and 267,060 disclose that flavonoid derivatives such as isocryptomerin, cryptomerin B, and amentoflavone derived from Selaginella tamariscina Spring can be efficiently used as immunosuppressants, antiin ⁇ flammatory agents, anticancer agents, and analgesics.
  • the present invention provides a composition for the prevention or treatment of acute or chronic degenerative brain diseases including an extract of Se ⁇ laginella tamariscina Spring as an effective ingredient.
  • a composition for preventing or treating an acute or chronic degenerative brain disease including as an effective ingredient an extract of Selaginella tamariscina Spring obtained by a process including: primarily extracting Selaginella tamariscina Spring with water or a C ⁇ C alcohol and secondarily extracting the primary extract with an organic solvent selected from the group consisting of hexane, chloroform, ethylacetate, and butanol, and a pharmaceutically acceptable carrier.
  • the extract of Selaginella tamariscina Spring contained as an effective ingredient in the composition of the present invention may be obtained by a known method, for example, a preparation process disclosed in Korean Patent No.
  • a solvent used in the primary extraction is water or a C ⁇ C alcohol.
  • the C ⁇ C alcohol may be methanol or ethanol.
  • the organic solvent used in the secondary extraction may be ethylacetate.
  • the primary extraction may be performed in a water bath once or more, preferably three times for 6-hour once.
  • the primary extract may be concentrated prior to the secondary extraction.
  • the secondary extraction may be performed as follows: the concentrate of the primary extract is suspended in distilled water, loaded onto a separating funnel, and extracted sequentially or separately with the above-exemplified organic solvents.
  • an extract of Selaginella tamariscina Spring contains flavonoid derivatives such as amentoflavone, cryptomerin B, and isocryptomerin.
  • the extract of Selaginella tamariscina Spring contained as an effective ingredient in the composition of the present invention strongly prevents the incidence of a cerebral damage relative to amentoflavone.
  • the composition of the present invention includes a pharmaceutically acceptable carrier, and may be administered orally or parenterally to human beings or animals for the prevention or treatment of acute or chronic degenerative brain diseases including dementia and stroke.
  • a composition for oral administration according to the present invention may be in any form including tablets, capsules, powders, granules, liquids, suspensions, gels, etc., and may include a conventional excipient such as a diluent, a disintegrating agent, a lubricant, etc.
  • the excipient includes a conventional diluent such as syrup, Arabic gum, gelatin, sorbitol, lactose, sugar, corn-starch, calcium phosphate, glycine, magnesium stearate, talc, polyethyleneglycol, silica, potato starch, or sodium lauryl sulfate, and a conventional flavorant or colorant.
  • a composition for parenteral admin ⁇ istration according to the present invention may be an isotonic solution or a sterile isotonic solution, and/or may include a conventional excipient such as a preservative or a stabilizer.
  • a pharmaceutical composition of the present invention can be administered in the form of a daily dosage of 100 mg-lg for average 70 kg adult for the prevention or treatment of acute or chronic degenerative brain diseases. However, an adequate dosage is determined depending on the type of disease and the degree of disease severity. In this regard, for typical adult patients, a unit dosage form includes about 100 mg to 1 g of the extract according to the present invention in combination with a pharmaceutically acceptable carrier. Description Of Drawings [15] FIG.
  • FIG. 1 is a graph illustrating the evaluation results for the inhibitory activity of an extract of Selaginella tamariscina Spring against nerve cell death induced by reactive oxygen species;
  • FIG. 2 is a graph illustrating the evaluation results for the inhibitory activity of an extract of Selaginella tamariscina Spring against nerve cell apoptosis;
  • FIG. 3 is a graph illustrating the evaluation results for an effect of an extract of Se ⁇ laginella tamariscina Spring on caspase-3 activity in several brain sections. Best Mode [18]
  • the present invention will be described more specifically with reference to the following Examples. The following Examples are for illustrative purposes and are not intended to limit the scope of the invention.
  • the term 'an extract of Selaginella tamariscina Spring' refers to 'an extract fraction of Selaginella tamariscina Spring' extracted from Selaginella tamariscina Spring using methanol as a primary extraction solvent and ethylacetate as a secondary extraction solvent according to a preparation process disclosed in Example 1 of Korean Patent No. 137,179.
  • Example 1 Evaluation of inhibitory activity of extract fraction of Selaginella tamarisdna Spring against nerve cell death caused by ischemic stimuli
  • the inhibitory activity of an extract fraction of Selaginella tamariscina Spring against nerve cell death induced by ischemia was evaluated.
  • SH-SY5Y cells (Korean Cell Line Bank (KCLB), No. 22266) were used as nerve cell lines.
  • the nerve cells were deposited in a volume of 5X10 cells/well in a 48-well plate.
  • DMEM media containing 5% fetal bovine serum and 10% horse serum were added thereto and the cell cultures were incubated at 37 0 C .
  • the cell culture media were replaced with serum-free DMEM media. Then, 0.5 mM of a hydrogen peroxide water solution was added thereto and the cell cultures were incubated for 24 hours.
  • MTT methylthiazoletetrazolium
  • DMSO dimethyl- sulfoxide
  • absorbance was measured at 595 nm.
  • An extract fraction of Selaginella tamariscina Spring was dissolved in DMSO. The mixed solution was added to the cells until the final concentration of the used compound was 1, 5, and 25 D / D and treated with a hydrogen peroxide water solution at one hour after the addition of the mixed solution to induce cell death. At this time, the final concentration of DMSO was adjusted to up to 0.5% to eliminate an influence of DMSO on cell death.
  • FIG. 1 An extract fraction of Selaginella tamariscina Spring exhibits an effective inhibitory activity against nerve cell death induced by reactive oxygen species.
  • FIG. 1 '*' indicates that cell death was inhibited at a significant level relative to a control (p ⁇ 0.05).
  • Nerve cell death can be morphologically classified into apoptosis and necrosis, and caspase-3 is a protease playing an important role in apoptotic cell death.
  • the nerve cell lines were treated with a cell culture (as a control) or an extract fraction of Selaginella tamariscina Spring (1, 5, 25 D / D ).
  • the cells were treated with 0.4 mM of a hydrogen peroxide water solution to induce cell death.
  • the cells were collected and dissolved in a buffer (10 mM HEPES pH7.4, 100 mM NaCl, 5 mM MgCl , 1% Triton X-100, 1 mM PMSF) to separate total proteins.
  • Caspase-3 activity was measured using a peptide substrate by fluorescent analysis and the results are shown in FIG. 2.
  • the hydrogen peroxide water solution remarkably increased caspase-3 activity, thereby leading to apoptotic cell death.
  • caspase-3 activity was remarkably reduced in a concentration-dependent manner.
  • '*' indicates that cell death was inhibited at a significant level relative to the control (p ⁇ 0.05).
  • the animal subjects were grouped into a control and two drug treatment groups.
  • a physiological saline was administered intraperitoneally to the Sprague-Dawley rats.
  • amentoflavone known to be contained in an extract fraction of Selaginella tamariscina Spring and an extract fraction of Selaginella tamariscina Spring were respectively ad ⁇ ministered intraperitoneally to the Sprague-Dawley rats in a dosage of 10 mg/kg.
  • the brains were excised from the rat heads. The degree of cerebral damage was evaluated by measuring Caspase-3 activity by fluorescent analysis and the results are shown in FIG. 3.
  • Example 3 Evaluation of inhibitory effect of an extract fraction of Selaginella tamariscina Spring against nerve cell death induced by betaamyloid
  • a ⁇ betaamyloid
  • nerve cell death was induced by be- taamyloid (A ⁇ ) peptides, and the inhibitory effect of an extract fraction of Se- laginella tamariscina Spring against the nerve cell death was evaluated.
  • a ⁇ be- taamyloid
  • the degree of nerve cell death induced by A ⁇ was measured using cell lines (PC12 cells, KCLB No. 21721) having similar characteristics to nerve cells.
  • the PC12 cells are deposited in a volume of 5X10 cells/well in a 48-well plate. Then, DMEM media containing 10% fetal bovine serum were added thereto and the cell cultures were incubated at 37 0 C .
  • the cell culture media were replaced with serum-free DMEM media.
  • a composition according to the present invention including an extract of Selaginella tamariscina Spring can effectively prevent nerve cell death induced by ischemia or be ⁇ taamyloid.
  • the physiological inhibitory activity of the extract of Selaginella tamariscina Spring against nerve cell death is attributed to a synergic effect of amentoflavone known to be contained in the extract and another ingredient(s) contained in the extract. Therefore, the composition according to the present invention can be effectively used for the prevention or treatment of acute or chronic degenerative brain diseases such as dementia or stroke.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Epidemiology (AREA)
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  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition destinée à prévenir ou traiter une maladie cérébrale dégénérative aiguë ou chronique, cette composition contenant, comme ingrédient actif, un extrait de Selaginella tamariscina Spring obtenu au moyen d'un procédé consistant d'abord à extraire Selaginella tamariscina Spring avec de l'eau ou un alcool C1-C4, puis à extraire le premier extrait avec un solvant organique choisi dans le groupe constitué par l'hexane, le chloroforme, l'éthylacétate et le butanol. Ladite composition comprend également un support pharmaceutiquement acceptable.
PCT/KR2005/001985 2004-06-28 2005-06-24 Composition destinee a prevenir ou traiter des maladies cerebrales degeneratives aigues ou chroniques et contenant un extrait de selaginella tamariscina spring Ceased WO2006001664A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020040048898A KR100633344B1 (ko) 2004-06-28 2004-06-28 권백 추출물을 포함하는 급성 또는 만성 퇴행성 뇌질환의 예방 또는 치료용 조성물
KR10-2004-0048898 2004-06-28

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WO2006001664A1 true WO2006001664A1 (fr) 2006-01-05

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115093462A (zh) * 2022-02-17 2022-09-23 西南民族大学 一种环肽类化合物及其制备方法和用途

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101487231B1 (ko) * 2012-01-03 2015-01-29 서웅진 부처손 추출물 또는 이의 분획물을 포함하는 스트레스로 인한 코티졸 과다 분비 억제를 통한 쿠싱증후군 개선용 약학적 조성물.
CN108498705A (zh) * 2018-05-10 2018-09-07 广东柏丽源美妆科技股份有限公司 阴道疑胶栓及其制作方法

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KR20050072175A (ko) * 2004-01-06 2005-07-11 이호섭 권백 추출물을 포함하는 뇌혈관계 질환의 예방 및 치료를위한 약학조성물

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KR20050072175A (ko) * 2004-01-06 2005-07-11 이호섭 권백 추출물을 포함하는 뇌혈관계 질환의 예방 및 치료를위한 약학조성물

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115093462A (zh) * 2022-02-17 2022-09-23 西南民族大学 一种环肽类化合物及其制备方法和用途
CN115093462B (zh) * 2022-02-17 2024-03-15 西南民族大学 一种环肽类化合物及其制备方法和用途

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KR20060000252A (ko) 2006-01-06
KR100633344B1 (ko) 2006-10-12

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