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WO2018048140A1 - Composition pharmaceutique destinée à la prévention ou au traitement des maladies osseuses - Google Patents

Composition pharmaceutique destinée à la prévention ou au traitement des maladies osseuses Download PDF

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Publication number
WO2018048140A1
WO2018048140A1 PCT/KR2017/009535 KR2017009535W WO2018048140A1 WO 2018048140 A1 WO2018048140 A1 WO 2018048140A1 KR 2017009535 W KR2017009535 W KR 2017009535W WO 2018048140 A1 WO2018048140 A1 WO 2018048140A1
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Prior art keywords
rankl
bone
group
extract
trees
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Korean (ko)
Inventor
정원윤
박광균
김형근
이주희
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Industry Academic Cooperation Foundation of Yonsei University
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Industry Academic Cooperation Foundation of Yonsei University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/40—Cornaceae (Dogwood 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
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • 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
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

Definitions

  • the present invention (a) at least one selected from rock horse claw, plum horse claw, apricot, cherry, radish, wild cherry, apricot, cherry tree, island cherry, oak, and Yoshino cherry tree (Rosales) plant group Plant extracts;
  • a pharmaceutical composition for the prevention or treatment of bone diseases including as an active ingredient any one or more extracts selected from the group consisting of locust and Carpinus plants It is about.
  • Osteoclast a multinucleated large cell, has the function of destroying and absorbing bone tissue, and is known to play a role in destroying bone matrix and degrading bone minerals.
  • Activated osteoclasts have three or more nuclei.
  • M-CSF macrophage colony stimulating factor
  • RNKL nuclear factor-kappa B
  • osteoclasts cause breakage and absorption of abnormal bone tissue due to imbalance with osteoblasts in the bone and thereby cause osteoporosis, in which bone mass and bone density decrease.
  • osteoclasts and osteoblasts can be caused by various causes such as bone metastasis of cancer cells, endocrine disorders, hyperparathyroidism, etc.
  • drugs and therapies that can effectively inhibit the destruction and absorption of bone tissue by osteoclasts have been actively studied for the treatment.
  • the treatment of bone damage caused by osteoclasts such as osteoporosis is widely used in the treatment of bisphosphonate-based drugs such as Fosamax (component name: aledronate), Actonel (component name: risedronate) and Zometa (component name: zoledronate).
  • osteoclasts are mostly used to induce the death of osteoclasts to delay or inhibit the loss of bone, and thus have various side effects such as osteonecrosis, severe atrial fibrillation, incapacitation of bones or joints, and pain in musculoskeletal pain. Causing problems (Coleman RE., Br J Cancer, 98: 1736-1740 (2008)).
  • osteoclasts are also promoted by cancer cells metastasized to bone in breast cancer, prostate cancer and the like, and serious bone diseases occur.
  • drugs for treating the same have not been developed.
  • One object of the present invention is to compensate for the disadvantages of the existing bisphosphonate series, by using any one or more natural extracts selected from the group consisting of rosewood plant extract, dogwood plant extract, ramie plant extract and hornberry plant extract side effects It is to provide a pharmaceutical composition for the prevention or treatment of significantly reduced bone disease.
  • the present inventors have found that when using any one or more extracts selected from the group consisting of rosewood plant extract, dogwood plant extract, ramie plant extract, and hornberry plant extract as an active ingredient, effectively inhibiting the formation of osteoclasts,
  • the present invention has been completed by discovering that the disease can be prevented or treated.
  • osteoblast refers to a cell that plays a role of destroying bone matrix and decomposing bone minerals to perform tissue destruction and absorption functions.
  • the osteoclasts have been reported to cause bone disease when an imbalance with osteoblasts occurs in the bone.
  • the bone disease is osteoporosis, osteomalacia, rickets, osteopenia, fibrotic osteoarthritis, aplastic bone disease, osteoplastic insufficiency, bone atrophy, paget's disease, periodontitis (periodontitis), rheumatoid arthritis ( rheumatoid arthritis), metabolic bone disease, and bone damage caused by bone metastasis of cancer cells, but may be any one or more selected from the group consisting of, but is not limited to any disease that may be caused by tissue destruction of osteoclasts and bone resorption. No.
  • the present invention is (a) rock horse claw, plum horse claw, dogwood, cherry, radish, wild cherry, apricot, island cherry, island cherry, oak, and Yoshino rose (Rosales) Any one or more plant extracts selected from the group of plants; (b) any one or more plant extracts selected from the group of Cornus plants consisting of bear horsetail, horsewood, dogwood, white horsewood, cornel and cornus; (c) any one or more plant extracts selected from the group of Boehmeria plants consisting of the herbaceous and turtle tails; And (d) any one or more plant extracts selected from the group consisting of acanthus and locusts (Carpinus) plant group; pharmaceutical composition for the prevention or treatment of bone diseases comprising at least one extract selected from the group consisting of To provide a composition.
  • the rock horse claw is one of the plants that grow seeds as a deciduous shrub, it is known to grow in the cracks of the foot of the mountain. It is about 1m high, hairy on small branches, old branches are greyish brown, and the opposite leaves are ovate about 3 ⁇ 6cm long and have serrated edges. Blooms in April-May, flowers are white. Planted for ornamental purposes and can be used for wheat circles.
  • the extract may be obtained by using any one or more of the leaves or flowers of the rock horsetail tree, and more preferably, the scientific name of the rock horsetail tree is Deutzia grandiflora var. baroniana Diels, but is not limited thereto.
  • the plum horse-valley (tree) is also called Danggangmok, and grows in the cracks of the mountains. At about 1 m in height, the bark is ash-colored and peels off irregularly. The leaves are opposite, oval or broad basal with fine serrates on the edges, and split into 4-6, 4-6 cm long on both sides. Flowers bloom in May and are white with 1 ⁇ 3 flowers on old branches. 1-2 flowers can be found under flowers.
  • the calyx tube is attached to the ovary, and the small peduncle is densely packed with the Virgin.
  • the extract may be obtained by using any one or more of the flowers or leaves of plum, more preferably, the scientific name of the plum may be Deutzia uniflora Shirai, but is not limited thereto.
  • the chanterelle grows in the vicinity of the village at the foot of the mountain or the height is 5-10m.
  • the bark is cork-developed, the small branches are brown, the leaves are alternate, broad egg-shaped, pointed, and have irregular ridges.
  • the length is 5-12cm, the leaf back is green and the petiole is 2-3cm long.
  • the flower is light red or white and blooms one by one before the leaves in April ⁇ May.
  • the small peduncle is about 8mm long, and the calyx is elliptical and has line-shaped serrate. Petals are round, 10-12 mm long.
  • the pistil is about 15mm long, similar to surgery, and the pistil is shaped like a goblet.
  • the ovary has hairs.
  • Fruit is a nucleus, egg-shaped, tastes astringent and ripens in yellow in July-August.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the apricot, more preferably the scientific name of the apricot is Prunus mandshurica var. glabra, but is not limited thereto.
  • cherry tree is a deciduous broad-leaved arboreous tree is native to Korea, distributed in Japan, China and inhabit in the mountainous region. Its height is 10-20m and it is peeled sideways in dark brown. Leaves are alternate, 6 ⁇ 12cm long egg-shaped or egg-shaped basso, with small hangers at the edges, and the back of leaves is grayish green. Flowers bloom in April or May in light pink or white with obstetric or umbel inflorescences, with stalks on peduncles and hairless in calyx tubes and pistils. Fruits are nucleus, ripened in June-July, rounded.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the cherry tree, and more preferably, the scientific name of the cherry tree is Prunus serrulata var. spontanea (Maxim.) E.H.Wilson, but is not limited thereto.
  • the radiant tree (Peach tree) is an arboreal deciduous tree belonging to the rosaceae, the height is about 6m, there is no hair on the small branches and there is hair on the dongah. Leaves are alternate, lanceolate, lanceolate, elliptic lanceolate, 8 ⁇ 15cm long, 1.5 ⁇ 3.5cm wide, with hairless on both sides and dull fine teeth on the edge.
  • the flower is light reddish and blooms before the leaves in April-May.
  • the fruit is a nucleus (a fruit with a hard shell covering the seeds). It is an egg-shaped round and ripens in August-September.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the radish tree, and more preferably, the scientific name of the radish tree may be Prunus persica (L.) BATSCH.
  • the present invention is not limited thereto.
  • the wild cherry tree is a deciduous broad-leaved large tall tree that grows in the high mountain forests of the country, the stem reaches 20m in height.
  • Stem bark dark brown, peeled off laterally, with long stems.
  • Leaves alternate and elliptical or obovate.
  • Petioles are hairless and reddish purple with a pair of honey glands on top. Flowers bloom white or light red in April-May, forming 2-3 inflorescences. Petals are round and have no fragrance. No hairs on peduncle, operating table, pistil, or ovary. Fruits are nucleus, ripening black and purple in May-June. It is distributed in Japan and Russia Sakhalin.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the wild cherry tree, more preferably the scientific name of the wild cherry tree may be Prunus sargentii Rehder, but is not limited thereto. It is not.
  • the apricot tree is a deciduous deciduous tree planted and grown near the house, the height is about 5m and the bark is reddish and the branches are reddish brown. Leaves alternate, broad oval or broad ovate. Flowers bloom pale red in April. Calyx leaves are 5 sheets, reddish purple, flipped backward. The petals are five and round. Fruits are rounded, with a diameter of about 3cm and ripen in yellow or reddish yellow in July. Planted in the sub-central region of Korea. Native to China, it is planted for ornamental purposes. Fruits are edible or medicinal, and wood is used as equipment.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the apricot tree, more preferably the scientific name of the apricot tree is Prunus armeniaca var. ansu Maxim. but is not limited thereto.
  • the island cherry tree grows in the forest, the height is about 10m and the bark is gray brown. Leaves are alternate, long oval, narrow at both ends, with fine jagged teeth on the edges, with hairs on the back venous fluid. Petiole is 8-12cm. Flowers bloom in May and are white and hang on inflorescences growing on old branches. Calyxes short, blunt, with tooth-shaped teeth. Petals are 5 pieces, elliptical, shorter than stamen, hairless in ovary. Fruits are round in nucleus, ripened in purple in July, and calyx and stamen remain. It is widely distributed in Korea (Jeju) and Japan.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the island cherry tree, more preferably the scientific name of the island cherry tree may be Prunus buergeriana Miq. It doesn't happen.
  • the island cherry is one of Ulleungdo's specialty plants, the height reaches 20m.
  • the bark is grayish brown, and the twig is grayish brown or grayish purple with no hairs.
  • Winter snow is long oval, without hairs.
  • Leaves are alternate, elliptical or egg-shaped, pointed with long tips, subcardia or basal, 8-15cm long, 4-9cm wide, without hairs on both sides.
  • the surface is green, the back is grayish green, and the teeth are hairy pointed.
  • Petiole is 2.5 ⁇ 3cm long, hairless, yellowish green, with stalk at the end. Flowers bloom later than leaves in April and are 2.5cm in diameter, white at first, but turn red when they fall.
  • peduncles There are no peduncles and 2-5 flowers are arranged in ridges.
  • Small peduncle is 15-18mm long, without hairs.
  • Calyx leaf is rolled backward without sawtooth, 5mm long, lanceolate triangular.
  • Calyx tube is 6-7mm long.
  • Petals are obovate or broad oval, 12-13mm long, with tips.
  • Surgery is 30 ⁇ 40, 5 ⁇ 10mm long, pistil is hairless and 1cm long.
  • Fruits are round or egg-shaped, pointed or rounded, 1 ⁇ 2cm long, 7mm wide, ripened in red in June. The small diameter is strong, 2cm long and 2mm in diameter.
  • the extract may be obtained using any one or more of the leaves, stems, bark, fruit, and root of the island cherry tree, and more preferably, the scientific name of the island cherry tree may be Prunus takesimensis NAKAI. It doesn't happen.
  • the oak tree reaches 10m in height and the bark is grayish brown with hairs on the branches.
  • Leaves are alternate, broad lanceolate or oval, serrated at the edges, with petioles and hairs at first.
  • the leaf veins are hairy and jagged.
  • Petals have hairs. The sepal is rounded at the bottom.
  • Petals are oval, concave in tip, 10-12mm long, with dense hairs on the lower part of pistil.
  • Fruits are round and ripen black in June-July. It is distributed in Korea (Jangsan cape, Yubongsan, Jirisan, Bogildo, Jeju) and Japan.
  • the extract may be obtained using any one or more of the leaves, stems, bark, fruit, and root of the cherry tree, and more preferably, the scientific name of the island cherry tree is Prunus pendula for. ascendens, but is not limited thereto.
  • the Yoshino cherry is a plant belonging to the genus Rosaceae (Prunus L.), most of which grow in the temperate regions of the northern hemisphere, it is known that the fruit or bark can be eaten.
  • the extract can be obtained using the leaves of the Yoshino cherry, more preferably the Yoshino cherry may be Prunus yedoensis Matsum, but is not limited thereto.
  • the cornel is a deciduous arborescent growing in the foothills of the sub-central region.
  • the growing environment is well exposed to the sun, grows in the rich side of the soil, the height is 3 ⁇ 8m, the leaves are egg or round shape, and the edges are wavy curves.
  • Flowers do not have peduncles, 20-30 branches at the end of twigs, 3-8cm long, 2 ⁇ 3cm long, white or white green, similar to the shape of petals.
  • the cornel fruit ripens in October in red and round, the bark surrounding the seeds is fleshy and edible. It may contain isoquercitrin and gallic acid, used for ornamental and industrial purposes, and fruit for edible and medicinal purposes.
  • the extract can be obtained using the leaves of the cornel, more preferably the scientific name of the cornel may be Cornus kousa F. Buerger ex Miquel, but is not limited thereto.
  • the bear's horsetail is also referred to as woosumok. It grows at the foot of a mountain or at the edge of a forest and is over 15m high.
  • the bark is grayish brown and splits irregularly vertically.
  • Leaves are 8-18cm long, green, opposite, oval or broad egg-shaped. Lying on the front of the leaf has fine hairs, and on the back there are many white and strong hairs.
  • Petiole is 1 ⁇ 3cm long and hairless. In June-August, four white flowers bloom at the tip of twigs in clusters. Inflorescence is 8-14cm in diameter, with 1 pistil and 4 stamens.
  • a peduncle is 3-4cm long and has no hairs. Petals are broad lanceolates.
  • Fruits are round, 6mm in diameter, ripen in bluish black in October. Seeds are round and concave. It is planted as a garden tree and wood is used as a craft material. It is distributed in Korea, Japan, Taiwan, and China.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the bear horsetail, more preferably the scientific name of the bear horsetail may be Cornus macrophylla, but is not limited thereto. It doesn't happen.
  • the dogwood grows in the valley, the height is about 10m.
  • the bark is blackish brown and split like a net. Leaves are opposite, broad egg-shaped or oval, with double hairs on both sides, flat edge, 4-5 pairs of veins. It is 5 ⁇ 8cm long, 3 ⁇ 5cm butterfly and white on the back. Petiole is 1-3cm long. Flowers bloom in May-June, white, and hang on inflorescences. A peduncle is 1.5 ⁇ 2.5cm long, and the petals are lanceolate. The pistil is shorter than the surgery and the operating table is similar in length to the petals. Fruits are nuclear, round, 6-7mm in diameter, ripen in September-October.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, and root of the dogwood, more preferably the scientific name of the dogwood may be Cornus walteri, but is not limited thereto. no.
  • the dogwood also grows in mountain valley forests. It reaches 20m in height and branches are spread out horizontally. Small branches are dark reddish purple in winter, and the branches flow in spring. Leaves are alternate, broad oval, pointed end. Leaves have flat edges, 5-8 rows of lateral veins, red petioles, white on the back of leaves. Fine hairs on both sides of leaves. Flowers bloom in May-June, white, and form inflorescences. The petals are wide lanceolate, with hairs on the outside with the calyx. There are 4 stamens, anther runs in T-type, and 1 pistil. Fruits are rounded to a nucleus and ripen purple. It is distributed in Korea, Japan, and China.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, fruit and root of the dogwood, more preferably the scientific name of the dogwood may be Cornus controversa, but is not limited thereto. It is not.
  • the white horsewood tree is also referred to as hongseom. It grows on mountainsides and is about 3m high.
  • the bark is red, the bone is white, and the young branch has no hair.
  • Leaves are opposite, oval or oval ellipsoid, 5 ⁇ 10cm long, 3 ⁇ 4cm butterfly.
  • the end is pointed, the bottom is round or wide wedge-shaped, and the edge is flat.
  • the outer side is green with lying hairs and the back side is white with fine hairs.
  • a side vein is 6 pairs, petiole is 1 ⁇ 2.5cm long, hairless. Flowers bloom in yellowish white in May-June, and hang on inflorescences in the shape of umbrellas at the ends of branches.
  • Inflorescences are 4-5cm in diameter, and small peduncles are 5-10mm in length. Calyx is divided into 4 branches, and the branch is pointed and short. Petals are 4 sheets, oval lanceolate, about 3mm long. There are 4 stamens, similar in length to the petals, pistil is shorter than the stamen, and the ovary is at the bottom. Fruits are elliptical nucleus, white or blueish white, ripening in August-September. Seeds are narrow and flat at both ends. Breed with seeds and hooks. Excellent ornamental value, planted as garden water, bark and leaves have anti-inflammatory, hemostatic action is also used as a herbal medicine.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, fruit and root of the white horsewood, more preferably the scientific name of the white horsewood may be Cornus alba, but It is not limited.
  • the cornus is the fruit of the cornus tree which is a deciduous arborescent of the dogwood.
  • Oval nucleus initially green, ripens red in August-October. Seeds are long oval, with ridges. Steamed with strong sweetness and strong acidity. Harvested after mid-October in October, meat and seeds are separated and meat is used for alcohol, tea and herbal medicine.
  • the pulp contains glycosides such as cornin, morroniside, loganin, tannin and saponin, and organic acids such as vitric acid, malic acid and tartaric acid. It also contains vitamin A and large amounts of sugar. Seeds contain palmitic acid, oleic acid, linoleic acid, and the like.
  • cornine is known to have an excitatory action of parasympathetic nerves. From ancient times, the herbal medicine was medicinal. Cornus trees are native to Korea and China, and are planted in sub-central Korea. In Korea, they are shipped as special products every year from Shandong-myeon, Gurye-gun, Jeollanam-do, Baeksa-myeon, Icheon-si, Gyeonggi-do, and Uiseong-gun, Gyeongsangbuk-do.
  • the extract may be obtained using any one or more of the leaves, stems, bark, fruit, fruit and root of the cornus, and more preferably the scientific name of the cornus may be Cornus officinalis, but is not limited thereto. .
  • the grass is a perennial plant mainly grows near the beach and is about 1 meter high.
  • the stems are gathered and the leaves are opposite, the leaves are oval, with regular teeth on the edges.
  • Fruits are achene, obovate, with white hairs on top.
  • the extract can be obtained using any one or more of the outpost, leaf, stem, bark, fruit, fruit and root of the seedlings, more preferably the scientific name of the seedlings Boehmeria platanifolia Franch. et Sav, but is not limited thereto.
  • the turtle tail (sesame leaf tree) has a height of 50 ⁇ 100cm and the stem is reddish brown, but may be brownish greenish brown, although the hair gradually disappears and the branches are thin. Leaves are opposite, rhombic egg-shaped, 4 ⁇ 8cm long, 2.5 ⁇ 4cm wide, with long ends like tails, and 5 ⁇ 6 large teeth on the edges. Lying hair on the front, hair on the veins on the back, petiole 1 ⁇ 3cm long, reddish. Flowers are female and female, but sometimes females and females bloom in July-August. Male inflorescences run on the leaf axil at the bottom of the stem. Female inflorescences hang on the leaf axil at the top of the stem.
  • the male flower has 4 pieces of fork and stamens, and the female flower runs in a group.
  • the ovary has one ovary and one pistil.
  • Fruits are aquatic, ripen in October, long egg-shaped, but several are gathered together and appear as several, with hairs at the end of the fruit. Originated from Korea, distributed in Korea, China, and Japan, inhabited near valley valleys and forest edges.
  • the extract can be obtained using any one or more of the turtle tail outpost, leaf, stem, bark, fruit, fruit and root, more preferably the scientific name of the turtle tail is oehmeria spicata (Thunb.) Thunb May be, but is not limited thereto.
  • the dogwood tree grows in the forest below the hillside. It is about 15m high and about 70cm in diameter.
  • the bark is ash-colored, rugged but not bursting with scattered white trunks.
  • the leaves are oval or long egg-shaped, 2 rows alternate, with pointed ends, thinly serrated, 4 ⁇ 8cm long.
  • Side veins are 12 ⁇ 15 pairs, with hairs growing on the front and back veins, and petioles are 4-12mm long and hairy.
  • Flowers are bisexual, bloomed in unknown flowers in April-May. A male spikelet has no stand and hangs up and hangs, and a female spikelet has a stand and is sparsely attached.
  • Fruits are nuts, inside the bark, broad egg-shaped, ripen in October.
  • Wood is dense, hard and elastic. It is used as utensils, grains, handwork, letterpress, and wood for shiitake cultivation. It is distributed in Korea (Jeonnam, Jeonbuk, Gyeongnam), Japan, and China.
  • the extract can be obtained using any one or more of the leaves, stems, bark, fruit, fruit and root of the dogwood tree, more preferably the scientific name of the dogwood tree may be Carpinus tschonoskii, but It is not limited.
  • seo tree is also referred to as seo tree and the origin of the tree name is not sure, but is assumed to mean a tree in the west. It grows mainly in mountains and is commonly found. Westerwood is used as an alley for shiitake mushroom cultivation, but its yield is lower than that of oak. Trees with similar shapes include the locust tree, magpie birch, and hawthorn. It is 15m high and 1m in diameter. The bark is gray and rugged like muscle. Leaves are alternate, 5.5 ⁇ 7.5cm long oval or long egg-shaped, pointed with long tips, plywood on the edge, hairy on the back vein. Flowers are male and female, bloom in May, running in doe inflorescences.
  • a male flower runs on a twig and sags downward.
  • a male flower runs one on each gun and has eight stamens, and the operating table is divided into two.
  • the female spikelet has a sack, two female flowers in each bag, and two pistils.
  • Fruit ears are long cylindrical, 4 ⁇ 8cm long, sagging down, 4 ⁇ 8 bracts with deeply sawed teeth on one side, and one projection under the opposite side.
  • Fruits are small, 3mm long, egg-shaped, ripen in October. It is distributed in Korea (Southern Yellow Sea), Japan, and China.
  • the extract may be obtained using any one or more of the leaves, stems, bark, fruit, fruit and root of the horn tree, and more preferably, the scientific name of the horn tree may be Carpinus laxiflora, but is not limited thereto. It is not.
  • the pharmaceutical composition according to the invention may be to inhibit differentiation into osteoclasts.
  • the extract according to the present invention preferably inhibits the activity of macrophage colony stimulating factor (M-CSF) and / or receptor activator of nuclear factor-kappa B ligand (RANKL) factors necessary for the differentiation of osteoclast precursor cells. It may be to inhibit the differentiation into osteoclasts through. However, there is no limitation as long as it can be used for the prevention and treatment of bone diseases by inhibiting the differentiation into osteoclasts.
  • M-CSF macrophage colony stimulating factor
  • RNKL nuclear factor-kappa B ligand
  • M-CSF macrophage colony stimulating factor
  • RANKL receptor activator of nuclear factor-kappa B ligand
  • RANKL receptor activator of nuclear factor-kappa B ligand
  • RANKL promotes differentiation into osteoclasts by activating transcription factors such as c-fos, nuclear factor of activated T-Cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), and nuclear factor kappa B (NF-kB), and PI3K.
  • the Cornus plant family consisting of bear horsetail, horsewood, dogwood, white horsewood, cornel and cornus;
  • Boehmeria flora consisting of hawthorn and turtle tails;
  • the powder is extracted with an organic solvent in a solvent extraction device or an accelerated solvent extractor (Accelerated Solution Extractor), and provides a method for producing a pharmaceutical composition for the prevention or treatment of bone diseases comprising the step of filtration.
  • the temperature of the solvent extraction device may be 30 ° C to 60 ° C, preferably 50 ° C, but is not limited thereto. If the temperature is 30 ° C or less, the temperature is not sufficiently raised, the active ingredient is not sufficiently dissolved in the organic solvent, if the temperature is 60 ° C or more, the components of the extract may be denatured.
  • the organic solvent used in the solvent extraction device may be ethanol or methanol, preferably ethanol, but is not limited thereto.
  • ethanol in the present invention there is an advantage that can be further improved the yield of the active ingredient contained in the extract compared to the case of using methanol.
  • the method may further comprise the step of concentrating the filtered filtrate.
  • the step of concentrating the filtrate may be a step of concentrating using a vacuum concentrator or a vacuum concentrator, but is not limited thereto.
  • the pharmaceutical composition of the present invention may be further co-administered with other anticancer agents, thereby effectively inhibiting general cancer cell proliferation and cancer metastasis, thereby being used for the treatment of cancer while treating bone damage caused by cancer.
  • the anticancer agent is nitrogen mustard, imatinib, oxaliplatin, rituximab, erlotinib, neratinib, lapatinib, zefitinib, vandetanib, nirotinib, semasanib, conservinib, axitinib, cediranib , Restautinib, trastuzumab, gefitinib, bortezomib, sunitinib, carboplatin, sorafenib, bevacizumab, cisplatin, cetuximab, biscumalboom, asparaginase, tretinoin, hydroxycarba Amide, dasatinib, estramastine, gemtuzumab ozogamycin, ibritumab tucetan, heptaplatin, methylaminolevulinic acid, amsacrine, alemtuzumab,
  • the pharmaceutical composition may be characterized in that the capsule, tablets, granules, injections, ointments, powder or beverage form, the pharmaceutical composition may be characterized in that it is intended for humans.
  • compositions of the present invention are not limited thereto, but may be used in the form of oral dosage forms, external preparations, suppositories, and sterile injectable solutions, such as powders, granules, capsules, tablets, and aqueous suspensions, respectively, according to conventional methods.
  • the pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers may be binders, suspending agents, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, flavors, etc.
  • compositions of the present invention may be prepared in various ways by mixing with a pharmaceutically acceptable carrier as described above.
  • oral administration may be in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and in the case of injectables, in the form of unit dose ampoules or multiple doses. have.
  • injectables in the form of unit dose ampoules or multiple doses.
  • Suitable carriers, excipients and diluents for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil and the like can be used.
  • fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like may be further included.
  • Routes of administration of the pharmaceutical compositions according to the invention include, but are not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, Sublingual or rectal. Oral or parenteral release is preferred.
  • parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intramuscular, intrasternal, intradural, intralesional and intracranial injection or infusion techniques.
  • the pharmaceutical compositions of the invention may also be administered in the form of suppositories for rectal administration.
  • the pharmaceutical compositions of the present invention vary depending on a number of factors, including the activity, age, weight, general health, sex, formulation, time of administration, route of administration, rate of release, drug combination and severity of the particular disease to be prevented or treated, of the specific compound employed.
  • the dosage of the pharmaceutical composition may be appropriately selected by those skilled in the art depending on the patient's condition, weight, extent of disease, drug form, route of administration and duration, and 0.0001 to 50 mg / kg per day or It may be administered at 0.001 to 50 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • the pharmaceutical compositions according to the invention may be formulated as pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions.
  • Another embodiment of the present invention provides a method for treating bone disease using the pharmaceutical composition, and the like.
  • the term "food composition” is used in various ways for improving and preventing bone diseases
  • the food composition comprising the composition of the present invention as an active ingredient includes various foods, for example, beverages, gums, teas, vitamins. It may be prepared in the form of a combination, powder, granules, tablets, capsules, sweets, rice cakes, bread and the like. Since the food composition of the present invention is configured from the conventional food intake which has little toxicity and no side effects, it can be used with confidence even for long-term use for prophylactic purposes.
  • the amount may be added at a ratio of 0.1 to 100% of the total weight.
  • natural carbohydrates include monosaccharides such as glucose, disaccharides such as fructose, sucrose, and the like, and common sugars such as polysaccharides, dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. can do.
  • flavourant examples include natural flavourant (tautin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).
  • natural flavourant tautin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)
  • synthetic flavoring agents sacharin, aspartame, etc.
  • These components may be used independently or in combination
  • the ratio of such additives is typically per 100 parts by weight of the composition of the present invention. It is generally selected from
  • the present invention is to inhibit the differentiation into osteoclasts using the pharmaceutical composition comprising any one or more natural extracts selected from the group consisting of rosewood plant extract, dogwood plant extract, ramie plant extract and hornberry plant extract Low side effects can effectively prevent or treat bone disease.
  • FIG. 1 is a view showing the results of confirming the toxicity of the rock horse claw and its related plant extract according to an embodiment of the present invention on the cells.
  • FIG. 2 is a view showing the results of confirming the toxicity of the cornel and its related plant extract according to an embodiment of the present invention on the cells.
  • Figure 3 is a view showing the results of confirming the toxicity of the seedling grass and its plant extract in accordance with an embodiment of the present invention on the cells.
  • FIG. 4 is a view showing the results of confirming the toxicity of the hawthorn and its related plant extracts on the cells according to an embodiment of the present invention.
  • FIG. 5 is a view showing the results of confirming the toxicity of the Yoshino cherry and its related plant extracts on the cells according to an embodiment of the present invention.
  • Figure 6 is a view showing the results confirming the osteoclast differentiation inhibitory effect of rock horse foot claw and its related plant extract according to an embodiment of the present invention.
  • Figure 7 is a view showing the results confirming the osteoclast differentiation inhibitory effect of rock horse claw and its related plant extract according to an embodiment of the present invention.
  • FIG. 8 is a view showing the results confirming the inhibitory effect of osteoclast differentiation of cornel and its related plant extract according to an embodiment of the present invention.
  • Figure 9 is a view showing the results confirming the inhibitory effect of osteoclast differentiation of cornel and its related plant extract according to an embodiment of the present invention.
  • FIG. 10 is a view showing the results of confirming the inhibitory effect of osteoclast differentiation of the seedling grass and its plant extract according to an embodiment of the present invention.
  • 11 is a view showing the results of confirming the inhibitory effect of osteoclast differentiation of the cultivars and the same plant extracts according to an embodiment of the present invention.
  • FIG. 12 is a view showing the results confirming the inhibitory effect of osteoclast differentiation of the hawthorn and its related plant extract according to an embodiment of the present invention.
  • Figure 13 is a view showing the results confirming the inhibitory effect of osteoclast differentiation of the hawthorn and its related plant extract according to an embodiment of the present invention.
  • FIG. 14 is a view showing the results confirming the inhibitory effect of osteoclast differentiation of Yoshino cherry tree and its related plant extract according to an embodiment of the present invention.
  • FIG. 15 is a view showing the results confirming the inhibitory effect of osteoclast differentiation of the Yoshino cherry and its related plant extract according to an embodiment of the present invention.
  • Botanical name Extraction Area Scientific name extraction Condition 7-1 Leather tree leaf Ailanthus altissima (Mill.) Swingle for. Altissima 2 7-4 Geoje Strawberry leaf Rubus longisepalus var. tozawai (Nakai) T.B.Lee 2 7-5 Oyster tree leaf Platycarya strobilacea Siebold & Zucc. var. strobilacea for. strobilacea 2 7-6 Gold leaf Ground Patrinia saniculaefolia Hemsl.
  • mouse bone marrow macrophages were isolated and cultured in the following process.
  • a three-week-old male ICR mouse (Naribiotech Co., Ltd.) was killed using a cervical dislocation, and the hind limb was peeled off using a forceps, and the hind limb was cut with surgical scissors to cut serum-free ⁇ -MEM ( minimum essential medium alpha (Gibco, USA).
  • ⁇ -MEM minimum essential medium alpha (Gibco, USA)
  • transfer to a new ⁇ -MEM transfer to a new ⁇ -MEM, and then put in a syringe (syringe) 600 ⁇ l of ⁇ -MEM inserted into the central spinal cord of the separated leg bone and sprayed 2 to 3 times Bone marrow cells were harvested.
  • the bone marrow cells extracted through the above process are placed into a new ⁇ -MEM, and a histopark (histopaque; Sigma) is used to separate the bone marrow macrophages from the bone marrow cells. -Aldrich, USA) was used to finally separate the bone marrow macrophages.
  • Bone marrow macrophages isolated by the above procedure were treated with 1% antibiotic-antimycotic (Gibco, USA), 10% fetal bovine serum (FBS) and Gibco, USA) and M-CSF ( Macrophage-colony stimulating factor (R & D system Inc., USA) was cultured in a 37 ° C., 5% CO 2 incubator with ⁇ -MEM nutrient medium containing 30ng / ml.
  • Example 2 Determine if the extract is cytotoxic
  • cytotoxicity experiments were performed.
  • Cell culture media was used Dulbecco's Modified Eagle's medium (DMEM) with 1% antibiotic-antibacterial solution and 10% FBS (fetal bovine serum).
  • DMEM Dulbecco's Modified Eagle's medium
  • FBS fetal bovine serum
  • 1 ⁇ 10 4 mouse macrophages were dispensed into each well of a 96-well plate and incubated for 24 hours at 37, 5% CO 2 conditions.
  • each extract was added to each concentration in a 96-well plate in which mouse macrophages were divided and further incubated for 24 hours.
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 1.059 ⁇ 0.117 100 Spoonbill Leaf, Flower One 1.326 ⁇ 0.252 125 3 1.333 ⁇ 0.129 126 5 1.309 ⁇ 0.050 124 10 1.547 ⁇ 0.147 146 20 1.768 ⁇ 0.064 167 40 2.075 ⁇ 0.262 196 80 1.817 ⁇ 0.296 172 Many-pumped stalk One 1.081 ⁇ 0.105 102 3 1.056 ⁇ 0.082 100 5 1.093 ⁇ 0.077 103 10 1.094 ⁇ 0.100 103 20 1.201 ⁇ 0.168 113 40 1.415 ⁇ 0.191 134 80 1.640 ⁇ 0.125 155 Plum Horse-footed Stem One 0.926 ⁇ 0.160 87 3 0.925 ⁇ 0.091 87 5 1.020 ⁇ 0.233 96 10 1.228 ⁇ 0.166 116 20 1.175 ⁇ 0.097 111 40 0.834 ⁇
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 1.102 ⁇ 0.156 100 Water stalk One 1.088 ⁇ 0.127 99 3 1.170 ⁇ 0.018 106 5 1.343 ⁇ 0.127 122 10 1.375 ⁇ 0.149 125 20 1.702 ⁇ 0.263 154 40 1.136 ⁇ 0.246 103 80 1.162 ⁇ 0.01 105 Rock Horsefoot Leaf One 1.127 ⁇ 0.138 102 3 1.104 ⁇ 0.13 100 5 1.276 ⁇ 0.102 116 10 1.276 ⁇ 0.036 116 20 1.631 ⁇ 0.131 148 40 1.592 ⁇ 0.133 144 80 1.975 ⁇ 0.143 179 Rock-footed Purlin One 0.953 ⁇ 0.208 86 3 1.276 ⁇ 0.224 116 5 1.265 ⁇ 0.051 115 10 1.36 ⁇ 0.134 123 20 1.489 ⁇ 0.073 135 40 1.305 ⁇ 0.139 118 80 2.297 ⁇ 0.235
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.912 ⁇ 0.064 100 Bear Dog Leaf One 0.926 ⁇ 0.038 102 3 1.168 ⁇ 0.058 128 5 1.15 ⁇ 0.024 126 10 1.809 ⁇ 0.116 198 20 2.251 ⁇ 0.113 247 40 2.266 ⁇ 0.086 248 80 1.236 ⁇ 0.119 135 Bear Dog Stem-Bark One 1.05 ⁇ 0.166 115 3 1.172 ⁇ 0.038 128 5 1.353 ⁇ 0.054 148 10 1.82 ⁇ 0.118 199 20 2.423 ⁇ 0.073 266 40 2.112 ⁇ 0.097 231 80 1.075 ⁇ 0.095 118 Dogwood Leaf, Stem One 0.963 ⁇ 0.093 106 3 1.023 ⁇ 0.011 121 5 1.165 ⁇ 0.115 134 10 1.187 ⁇ 0.058 130 20 1.473 ⁇ 0.176 161 40 1.466 ⁇
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.836 ⁇ 0.05 100 Cornel leaves One 0.842 ⁇ 0.124 101 3 1.069 ⁇ 0.085 128 5 1.01 ⁇ 0.119 121 10 1.378 ⁇ 0.093 165 20 1.469 ⁇ 0.092 176 40 1.213 ⁇ 0.124 145 80 0.943 ⁇ 0.108 113 Cornel bark-bark One 0.8 ⁇ 0.115 96 3 0.88 ⁇ 0.033 105 5 0.904 ⁇ 0.128 108 10 1.068 ⁇ 0.084 128 20 1.059 ⁇ 0.109 127 40 1.481 ⁇ 0.082 177 80 1.938 ⁇ 0.135 232 Cornus leaves, stem One 0.778 ⁇ 0.024 93 3 0.961 ⁇ 0.089 115 5 1.156 ⁇ 0.048 138 10 1.575 ⁇ 0.119 188 20 1.607 ⁇ 0.126 192 40 1.435 ⁇
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 1.43 ⁇ 0.031 100
  • Mossy Grass Outpost One 0.835 ⁇ 0.031 58 5 1.249 ⁇ 0.137 87 10 1.126 ⁇ 0.091 79 50 1.849 ⁇ 0.134 129 100 2.171 ⁇ 0.2 152
  • Ciliary grass One 1.832 ⁇ 0.026 128 5 1.692 ⁇ 0.025 118 10 1.713 ⁇ 0.1 120 50 1.46 ⁇ 0.101 102 100 1.2 ⁇ 0.183
  • Outcrop One 1.691 ⁇ 0.086 118 5 1.674 ⁇ 0.094 117 10 1.55 ⁇ 0.082 108 50 0.19
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 1.403 ⁇ 0.185 100 Bark tree trunk-bark
  • Cell survival rate (%) - - 1.403 ⁇ 0.185 100 Bark tree trunk-bark
  • Clover leaf, stem One 1.336 ⁇ 0.104 95 3 1.49 ⁇ 0.054 106 5 1.585 ⁇ 0.124 113 10 1.316 ⁇ 0.231 94 20 0.815 ⁇ 0.031 58 40 0.29 ⁇ 0.082 21 80 0.288 ⁇ 0.059 20
  • Magpie branch One 1.22 ⁇ 0.079 87 3 1.214 ⁇ 0.213 86 5 1.223 ⁇ 0.211 87 10 1.424 ⁇ 0.173 101
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.95 ⁇ 0.064 100 West tree flower One 1.359 ⁇ 0.022 143 3 1.43 ⁇ 0.218 150 5 1.241 ⁇ 0.228 131 10 1.417 ⁇ 0.17 149 20 1.526 ⁇ 0.17 161 40 0.868 ⁇ 0.117 91 80 0.175 ⁇ 0.048 18 West tree leaf One 1.304 ⁇ 0.163 137 3 1.366 ⁇ 0.129 144 5 1.16 ⁇ 0.066 122 10 1.187 ⁇ 0.196 125 20 1.219 ⁇ 0.2 128 40 1.336 ⁇ 0.132 141 80 0.589 ⁇ 0.136 62 West Tree Trunk-Bark One 0.91 ⁇ 0.146 96 3 0.98 ⁇ 0.085 103 5 1.13 ⁇ 0.105 119 10 1.359 ⁇ 0.07 143 20 1.595 ⁇ 0.095 168 40 0.147 ⁇ 0.007 16 80 0.126 ⁇ 0.003 13
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.842 ⁇ 0.039 100 Cherry tree trunk-bark One 0.902 ⁇ 0.055 107 3 1.11 ⁇ 0.066 132 5 1.119 ⁇ 0.036 133 10 1.453 ⁇ 0.059 173 20 1.741 ⁇ 0.067 207 40 2.004 ⁇ 0.141 238 80 2.219 ⁇ 0.127 264 Apricot leaves One 0.874 ⁇ 0.043 104 3 0.87 ⁇ 0.108 103 5 0.874 ⁇ 0.123 104 10 0.905 ⁇ 0.107 108 20 0.996 ⁇ 0.085 118 40 1.143 ⁇ 0.102 136 80 2.05 ⁇ 0.064 244 Apricot stem One 0.725 ⁇ 0.072 86 3 0.845 ⁇ 0.067 100 5 0.932 ⁇ 0.116 111 10 1.14 ⁇ 0.037 135 20 1.142 ⁇ 0.078 136 40 1.764 ⁇ 0.077
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.734 ⁇ 0.094 100 Cherry tree leaves One 0.56 ⁇ 0.034 76 3 0.575 ⁇ 0.059 78 5 0.767 ⁇ 0.059 104 10 1.044 ⁇ 0.075 142 20 1.149 ⁇ 0.098 157 40 1.631 ⁇ 0.096 222 80 1.996 ⁇ 0.136 272 Cherry trunks-bark One 0.812 ⁇ 0.048 111 3 0.936 ⁇ 0.13 127 5 0.987 ⁇ 0.102 134 10 1.458 ⁇ 0.122 199 20 1.511 ⁇ 0.051 206 40 1.63 ⁇ 0.108 222 80 1.808 ⁇ 0.11 246 Radish flowers One 0.729 ⁇ 0.109 99 3 0.819 ⁇ 0.036 112 5 0.77 ⁇ 0.055 105 10 0.802 ⁇ 0.137 109 20 0.792 ⁇ 0.04 108 40 1.144 ⁇ 0.115 156 80
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.713 ⁇ 0.05 100 Wild cherry tree leaves One 0.73 ⁇ 0.045 102 3 0.876 ⁇ 0.017 123 5 1.058 ⁇ 0.088 148 10 1.194 ⁇ 0.105 167 20 1.329 ⁇ 0.03 186 40 2.036 ⁇ 0.04 285 80 2.181 ⁇ 0.111 306 Wild cherry tree One 0.866 ⁇ 0.051 121 3 0.888 ⁇ 0.103 124 5 1.133 ⁇ 0.06 159 10 1.345 ⁇ 0.067 189 20 1.532 ⁇ 0.098 215 40 2.083 ⁇ 0.067 292 80 2.219 ⁇ 0.058 311 Apricot leaves One 0.823 ⁇ 0.124 115 3 0.873 ⁇ 0.152 122 5 0.915 ⁇ 0.047 128 10 0.891 ⁇ 0.13 125 20 1.078 ⁇ 0.1 151 40 1.345 ⁇ 0.008 189 80 1.467
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 1.203 ⁇ 0.089 100 Sakura cherry leaf One 1.348 ⁇ 0.195 112 3 1.369 ⁇ 0.197 114 5 1.548 ⁇ 0.123 129 10 1.628 ⁇ 0.019 135 20 1.69 ⁇ 0.159 141 40 1.841 ⁇ 0.104 153 80 2.331 ⁇ 0.201 194 Iris cherry tree trunk-bark One 1.209 ⁇ 0.136 101 3 1.478 ⁇ 0.232 123 5 1.627 ⁇ 0.127 135 10 1.769 ⁇ 0.189 147 20 1.578 ⁇ 0.061 131 40 2.392 ⁇ 0.032 199 80 3.04 ⁇ 0.078 253 Island cherry leaf One 1.166 ⁇ 0.175 97 3 1.476 ⁇ 0.073 123 5 1.478 ⁇ 0.147 123 10 1.671 ⁇ 0.074 139 20 1.546 ⁇ 0.072 129 40 1.936 ⁇ 0.091 161
  • Botanical name Extract concentration ( ⁇ g / ml) Absorbance value Cell survival rate (%) - - 0.921 ⁇ 0.052 100 Yeonna Leaf, stem One 1.092 ⁇ 0.065 118 3 1.02 ⁇ 0.155 111 5 1.194 ⁇ 0.116 130 10 1.478 ⁇ 0.118 160 20 1.774 ⁇ 0.087 193 40 2.346 ⁇ 0.171 255 80 2.405 ⁇ 0.139 261 Cherry tree trunk-bark One 1.099 ⁇ 0.121 119 3 1.198 ⁇ 0.126 130 5 1.132 ⁇ 0.119 123 10 1.804 ⁇ 0.215 196 20 2.156 ⁇ 0.355 234 40 3.029 ⁇ 0.05 329 80 3.104 ⁇ 0.052 337 Cherry tree leaves, stem One 1.066 ⁇ 0.098 116 3 1.097 ⁇ 0.065 119 5 1.063 ⁇ 0.076 115 10 1.635 ⁇ 0.169 177 20 2.079 ⁇ 0.02 226 40 2.109 ⁇ 0.107 229 80 2.
  • osteoclast differentiation inhibition assay was performed ( See, Park EK. Et al., Biochem Biophys Res Commun., 325 (4): 1472-1480 (2004).
  • Bone marrow macrophages prepared by the method of Example 1 were dispensed by 5 ⁇ 10 4 cells / well in 96-well for differentiation inhibition rate experiment. Each extract was then mixed in ⁇ -MEM (1% antibiotic-antibacterial solution, 10% FBS, 30 ng / ml M-CSF, 50 ng / ml RANKL addition) medium by concentration to a final volume of 200 ⁇ l. After the preparation, the treated bone marrow macrophages were treated and replaced with fresh medium every two days in a cell incubator at 37, 5% CO 2 condition and finally cultured for 5 days to prepare an experimental group.
  • ⁇ -MEM 1% antibiotic-antibacterial solution, 10% FBS, 30 ng / ml M-CSF, 50 ng / ml RANKL addition
  • Negative controls were prepared by culturing cells using ⁇ -MEM with 1% antibiotic-antibacterial solution, 10% FBS, and 30ng / ml M-CSF, and positive controls 1% antibiotic-antibacterial.
  • the solution, 10% FBS, 30ng / ml of M-CSF, and ⁇ -MEM with 50ng / ml of RANKL was incubated under the same conditions as the experimental group.
  • the cultured cells were measured using a TRAP assay kit (tartrate resistant acid phosphatase assay kit; Sigma-Aldrich, USA), followed by measuring the number of osteoclasts corresponding to three or more nuclei using an optical microscope. 6 to 15 and Tables 16 to 21 are shown.
  • the leaf extract of hawthorn hawthorn and the leaf extract of rock hawthorn had an inhibition of osteoclast differentiation of 80% or more at a concentration of 40 ⁇ g / ml. Confirmed to show. Through the above results, it was confirmed that even in the same plants, different osteoclast differentiation inhibition rates, and among the same plants of the rock herbaceous tree, the extracts of the rock herbaceous tree and the plum anemone tree can be used for the prevention or treatment of bone diseases. .
  • Botanical name Extract concentration ( ⁇ g / ml) Number of osteoclasts induced by RANKL % Inhibition of differentiation into osteoclasts 0 ⁇ 0 RANKL 247 ⁇ 8 0 Cypress, flower RANKL + 10 239 ⁇ 1 3 RANKL + 20 244 ⁇ 6
  • the leaf and stem extracts of the white horseradish tree, the leaf extracts of the cornel and the extracts of the stems and the bark (bark) showed significantly higher inhibition of differentiation, whereas the fruit extracts of the cornel tree showed low osteoclast differentiation inhibition. In this way, it was confirmed that even the same plant had different effects depending on the tissues of leaves and stems. In addition, it was confirmed that the leaves and stem extracts and fruit extracts of cornus milk showed high osteoclast differentiation inhibition rate.
  • Botanical name Extract concentration ( ⁇ g / ml) Number of osteoclasts induced by RANKL % Inhibition of differentiation into osteoclasts - - 0 ⁇ 0 - - RANKL 252 ⁇ 4 0 Bear Dog Leaf RANKL + 10 9 ⁇ 1 97 RANKL + 20 0 ⁇ 0 100 RANKL + 40 0 ⁇ 0 100 Bear Dog Stem-Bark RANKL + 10 0 ⁇ 0 100 RANKL + 20 0 ⁇ 0 100 RANKL + 40 0 ⁇ 0 100 Dogwood Leaf, Stem RANKL + 10 138 ⁇ 11 45 RANKL + 20 7 ⁇ 2 97 RANKL + 40 0 ⁇ 0 100 Dogwood Stem-bark RANKL + 10 0 ⁇ 0 100 RANKL + 20 0 ⁇ 0 100 RANKL + 40 0 ⁇ 0 100 Dogwood Leaf, Stem RANKL + 10
  • Botanical name Extract concentration ( ⁇ g / ml) Number of osteoclasts induced by RANKL % Inhibition of differentiation into osteoclasts - - 0 ⁇ 0 - - RANKL 199 ⁇ 2 0 Mossy Grass Outpost RANKL + 5 197 ⁇ 11 One RANKL + 10 197 ⁇ 5 One RANKL + 20 134 ⁇ 10 32 RANKL + 50 98 ⁇ 10 51 Wangmosi Pool Outpost RANKL + 0.1 187 ⁇ 14 6 RANKL + 0.5 178 ⁇ 9 11 RANKL + 1 174 ⁇ 18 13 Ciliary grass RANKL + 5 179 ⁇ 10 10 RANKL + 10 179 ⁇ 10 10 RANKL + 20 151 ⁇ 15 24 RANKL + 50 145 ⁇ 15 27 Outcrop RANKL + 5 196 ⁇ 10 One RANKL + 10 164 ⁇ 10 17 RANKL + 20 133
  • Botanical name Extract concentration ( ⁇ g / ml) Number of osteoclasts induced by RANKL % Inhibition of differentiation into osteoclasts - - 0 ⁇ 0 - - RANKL 267 ⁇ 4 0 Bark tree trunk-bark RANKL + 5 255 ⁇ 6 4 RANKL + 10 88 ⁇ 11 67 RANKL + 20 42 ⁇ 8 84 Clover leaf, stem RANKL + 5 244 ⁇ 8 9 RANKL + 10 87 ⁇ 4 68 RANKL + 20 0 ⁇ 0 100 Magpie branch RANKL + 5 169 ⁇ 1 37 RANKL + 10 170 ⁇ 5 37 RANKL + 20 103 ⁇ 8 62 Blackcurrant leaves RANKL + 5 239 ⁇ 1 10 RANKL + 10 223 ⁇ 4 16 RANKL + 20 149 ⁇ 2 44 West tree flower RANKL + 10 233 ⁇ 6 13 RANKL + 20 157
  • the leaf extract and stem extract of the apricot As shown in Fig. 14, Fig. 15, Table 20 and Table 21, among the Yoshino cherry tree and its related plants, the leaf extract and stem extract of the apricot, the stem (bark) extract and the leaf extract of the cherry tree, the stem (bark) of the radish tree Extract, Leaf Extract and Stem Extract of Apricot Tree, Leaf Extract of Apricot Tree, Bark Extract of Sakura Cherry, Bark Extract of Sakura Cherry, Stem Extract of Bark Cherry, Stem Extract of Yoshino Cherry It was confirmed that the osteoclast differentiation rate was high.
  • Botanical name Extract concentration ( ⁇ g / ml) Number of osteoclasts induced by RANKL % Inhibition of differentiation into osteoclasts - - 0 ⁇ 0 - - RANKL 269 ⁇ 10 0 Cherry tree trunk-bark RANKL + 10 244 ⁇ 5 9 RANKL + 20 208 ⁇ 10 23 RANKL + 40 108 ⁇ 6 60 Apricot leaves RANKL + 10 193 ⁇ 16 28 RANKL + 20 129 ⁇ 21 52 RANKL + 40 13 ⁇ 2 95 Apricot stem RANKL + 10 169 ⁇ 1 37 RANKL + 20 46 ⁇ 8 83 RANKL + 40 14 ⁇ 3 95 Apricot Stem-Bark RANKL + 10 221 ⁇ 4 18 RANKL + 20 137 ⁇ 5 49 RANKL + 40 25 ⁇ 2 91 Oak leaves, stems, flowers RANKL + 10 237 ⁇ 5 12 RANKL + 20
  • Botanical name Extract concentration ( ⁇ g / ml) Number of osteoclasts induced by RANKL % Inhibition of differentiation into osteoclasts - - 0 ⁇ 0 - - RANKL 269 ⁇ 10 0 Island Cherry Tree Trunk RANKL + 10 180 ⁇ 13 33 RANKL + 20 159 ⁇ 4 41 RANKL + 40 53 ⁇ 4 80 Gingko leaf, stem RANKL + 10 189 ⁇ 8 30 RANKL + 20 172 ⁇ 12 36 RANKL + 40 106 ⁇ 4 61 Yeonna Leaf, stem RANKL + 10 251 ⁇ 6 7 RANKL + 20 271 ⁇ 2 0 RANKL + 40 194 ⁇ 8 28 Cherry tree trunk-bark RANKL + 10 267 ⁇ 4 One RANKL + 20 187 ⁇ 9 31 RANKL + 40 48 ⁇ 6 82 Cherry tree leaves, stem RANKL + 10 261 ⁇ 15 3 RANKL +
  • each of the extracts are not cytotoxic or at high concentrations, such as cornel leaves, oyster tree leaves, rockberry leaves and flowers, ivy leaf leaves and stems, Yoshino leaves, pine needles, leather leaves, and hazel leaves. In particular, it was confirmed that more effectively inhibit the differentiation into osteoclasts.
  • the use of the extracts according to the present invention can effectively inhibit the differentiation of macrophages from osteoclasts with low side effects.
  • the extracts according to the present invention effectively prevent and treat bone diseases. It was confirmed that it could be used.
  • the present invention is to inhibit the differentiation into osteoclasts using the pharmaceutical composition comprising any one or more natural extracts selected from the group consisting of rosewood plant extract, dogwood plant extract, ramie plant extract and hornberry plant extract
  • the pharmaceutical composition comprising any one or more natural extracts selected from the group consisting of rosewood plant extract, dogwood plant extract, ramie plant extract and hornberry plant extract

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Abstract

La présente invention concerne une composition pharmaceutique destinée à prévenir ou à traiter les maladies osseuses et une composition alimentaire destinée à soulager ou à atténuer les maladies osseuses, les compositions permettant aux effets secondaires du traitement d'être remarquablement réduits en utilisant un ou plusieurs extraits d'origine naturelle sélectionnés dans le groupe constitué d'un extrait végétal de l'ordre des Rosales, d'un extrait végétal du genre Cornus, d'un extrait végétal du genre Boehmeria, et d'un extrait végétal du genre Carpinus. Lorsque les compositions sont utilisées, la différenciation en ostéoclastes est efficacement inhibée, permettant ainsi la prévention ou le traitement efficace des maladies osseuses.
PCT/KR2017/009535 2016-09-07 2017-08-31 Composition pharmaceutique destinée à la prévention ou au traitement des maladies osseuses Ceased WO2018048140A1 (fr)

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CN118415341A (zh) * 2024-06-27 2024-08-02 朗姿赛尔生物科技（广州）有限公司 一种增加骨密度的组合物、保健食品及其制备方法

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KR102186886B1 (ko) * 2018-07-11 2020-12-04 한국 한의학 연구원 프루누스 자마사쿠라 추출물을 유효성분으로 함유하는 골다공증의 예방, 개선 또는 치료용 조성물
KR20200064776A (ko) * 2018-11-29 2020-06-08 경희대학교 산학협력단 도인 추출물을 포함하는 골절 예방, 개선 또는 치료용 조성물
KR20200099357A (ko) 2019-02-14 2020-08-24 경북대학교 산학협력단 벚나무 껍질 추출물을 유효성분으로 포함하는 알레르기 질환의 예방 또는 치료용 약학적 조성물
KR102415187B1 (ko) * 2019-06-25 2022-07-01 아주대학교산학협력단 유백피 및 산수유 복합추출물을 유효성분으로 함유하는 골질환 예방 또는 치료용 조성물
EP4000622A4 (fr) * 2019-07-15 2022-10-05 Industry Foundation of Chonnam National University Composition pharmaceutique destinée à la prévention ou au traitement des maladies osseuses
KR102481063B1 (ko) 2020-06-30 2022-12-27 한국콜마주식회사 살구나무꽃의 향취를 재현한 향료 조성물
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KR102672417B1 (ko) * 2021-12-16 2024-06-07 가톨릭관동대학교산학협력단 층층나무 추출물을 포함하는 혈관 석회화의 예방 또는 치료용 조성물

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CN118415341A (zh) * 2024-06-27 2024-08-02 朗姿赛尔生物科技（广州）有限公司 一种增加骨密度的组合物、保健食品及其制备方法

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