Pharmaceutical composition for preventing or treating bone-related diseases
阅读说明：本技术 用于预防或治疗骨相关疾病的药物组合物 (Pharmaceutical composition for preventing or treating bone-related diseases ) 是由 徐廷泽 文硕晙 金圣镇 于 2018-05-30 设计创作，主要内容包括：本发明涉及一种用于预防或治疗骨相关疾病的药物组合物；其促进前成骨细胞分化为成骨细胞以诱导产生矿化结节,并且在同时抑制骨髓细胞分化为破骨细胞和抑制破骨细胞的功能,从而有效控制骨内稳态并在预防或治疗骨相关疾病中十分有用。此外,本发明还涉及一种用于预防或治疗更年期疾病(尤其是更年期骨疾病)的药物组合物；其中所述药物组合物提升海绵状骨体积和促进前成骨细胞的分化为成骨细胞以诱导产生矿化结节,并同时抑制骨髓细胞分化为破骨细胞抑制和破骨细胞的功能,从而有效控制骨内稳态并在预防或治疗骨相关疾病中十分有用。(The present invention relates to a pharmaceutical composition for preventing or treating bone-related diseases; it promotes differentiation of preosteoblasts into osteoblasts to induce the production of mineralized nodules, and is very useful in simultaneously inhibiting differentiation of bone marrow cells into osteoclasts and inhibiting the function of osteoclasts, thereby effectively controlling bone homeostasis and in preventing or treating bone-related diseases. In addition, the present invention relates to a pharmaceutical composition for preventing or treating a climacteric disorder (particularly a climacteric bone disorder); wherein the pharmaceutical composition promotes the spongy bone volume and promotes the differentiation of preosteoblasts into osteoblasts to induce the production of mineralized nodules, and simultaneously inhibits the differentiation of bone marrow cells into osteoclast inhibition and osteoclast function, thereby effectively controlling bone homeostasis and being very useful in the prevention or treatment of bone-related diseases.)
1. A pharmaceutical composition for preventing or treating bone-related diseases, comprising as active ingredients:
sterol sulfates.
2. The pharmaceutical composition of claim 1, wherein the sterol is at least one selected from the group consisting of: campesterol, sitosterol, stigmasterol, and cholesterol.
3. The pharmaceutical composition of claim 1, wherein the sterol sulfate is represented by formula 1:
[ formula 1]
4. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition promotes differentiation of preosteoblasts into osteoblasts.
5. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition inhibits differentiation of bone marrow cells into osteoclasts.
6. The pharmaceutical composition of claim 1, wherein the bone-related disease is at least one selected from the group consisting of: osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrodysplasia, paget's disease, hypercalcemia, bone tumor destruction, cancer-related bone resorption diseases, bone fractures, osteolysis, osteoarthritis and rheumatoid arthritis.
7. The pharmaceutical composition of claim 6, wherein the osteoporosis is at least one selected from the group consisting of: primary osteoporosis due to aging, primary osteoporosis due to menopause, primary osteoporosis due to ovariectomy, and primary osteoporosis due to orchiectomy.
8. The pharmaceutical composition of claim 6, wherein the osteoporosis is at least one selected from the group consisting of: glucocorticoid-induced osteoporosis, hyperthyroidism-associated osteoporosis, retention osteoporosis, heparin-induced osteoporosis, immunosuppression-induced osteoporosis, renal insufficiency-induced osteoporosis, inflammatory osteoporosis, Cushing's syndrome-induced osteoporosis, rheumatoid osteoporosis, and estrogen synthesis inhibitor-induced osteoporosis.
9. The pharmaceutical composition of claim 1, wherein the sterol sulfate is contained at a concentration of 1 μ Μ to 1 mM.
10. A food composition for preventing or improving a bone-related disease, comprising as active ingredients:
sterol sulfates.
11. The food composition of claim 10, wherein the sterol is at least one selected from the group consisting of: campesterol, sitosterol, stigmasterol, and cholesterol.
12. The food composition of claim 10, wherein the sterol sulfate is represented by formula 1:
[ formula 1]
13. The food composition of claim 10, wherein the food composition promotes differentiation of preosteoblasts to osteoblasts.
14. The food composition of claim 10, wherein the food composition inhibits differentiation of bone marrow cells into osteoclasts.
15. The food composition of claim 10, wherein the bone-related disorder is at least one selected from the group consisting of: osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrodysplasia, paget's disease, hypercalcemia, bone tumor destruction, cancer-related bone resorption diseases, bone fractures, osteolysis, osteoarthritis and rheumatoid arthritis.
16. A composition for promoting bone regeneration, comprising as active ingredients:
sterol sulfates.
17. The composition of claim 16, wherein the sterol is at least one member selected from the group consisting of: campesterol, sitosterol, stigmasterol, and cholesterol.
18. The composition of claim 16, wherein the sterol sulfate is according to formula 1:
[ formula 1]
19. A pharmaceutical composition for preventing or treating climacteric disorders, which comprises as active ingredients:
sterol sulfatase inhibitors.
20. The pharmaceutical composition of claim 19, wherein said sterol sulfatase inhibitor is at least one selected from the group consisting of: AHBS (C)6H7NO4S), danazol (C)22H27NO2)、EMATE(C18H23NO4S), Erolfsta (C1)4H15NO5S)、KW-2581(C25H36N2O4S), progesterone (C)21H30O2)、SR-16157(C28H46N2O4S)、STX213(C28H46N2O4S)、STX681(C16H13BrN6O3S), and a compound of formula 2:
[ formula 2]
21. The pharmaceutical composition of claim 20, wherein the compound of formula 2 is 6-oxo-6, 7,8,9,10, 11-hexahydrocyclohepta [ c ] chromen-3-yl sulfamate.
22. The pharmaceutical composition according to claim 19, wherein the climacteric disorder is a climacteric bone disorder, and the bone disorder is at least one selected from the group consisting of: osteoporosis type I due to menopause, osteoporosis type I due to ovariectomy, spinal stenosis, spinal compression fracture, and osteoarthritis.
23. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition increases trabecular bone volume.
24. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition promotes differentiation of preosteoblasts into osteoblasts.
25. The pharmaceutical composition according to claim 19, wherein the pharmaceutically acceptable salt thereof,
wherein the pharmaceutical composition inhibits differentiation of bone marrow cells into osteoclasts.
26. A food composition for preventing or improving a climacteric disorder, comprising as active ingredients:
sterol sulfatase inhibitors.
27. The food composition of claim 26, wherein the sterol sulfatase inhibitor is at least one selected from the group consisting of: AHBS (C)6H7NO4S), danazol (C)22H27NO2)、EMATE(C18H23NO4S), Erolesta (C)14H15NO5S)、KW-2581(C25H36N2O4S), progesterone (C)21H30O2)、SR-16157(C28H46N2O4S)、STX213(C28H46N2O4S)、STX681(C16H13BrN6O3S), and a compound of formula 2:
[ formula 2]
28. The food composition of claim 27, wherein the compound of formula 2 is 6-oxo-6, 7,8,9,10, 11-hexahydrocyclohepta [ c ] chromen-3-yl sulfamate.
29. The food composition according to claim 26, wherein the climacteric disorder is a climacteric bone disorder, and the bone disorder is at least one selected from the group consisting of: osteoporosis type I due to menopause, osteoporosis type I due to ovariectomy, spinal stenosis, spinal compression fracture, and osteoarthritis.
30. The food composition of claim 26, wherein the food composition increases trabecular bone volume.
31. The food composition of claim 26, wherein the food composition promotes differentiation of preosteoblasts to osteoblasts.
32. The food composition of claim 26, wherein the food composition inhibits differentiation of bone marrow cells into osteoclasts.
33. A pharmaceutical composition for preventing or treating bone-related diseases, comprising as active ingredients:
sterol sulfates; and
sterol sulfatase inhibitors.
34. The pharmaceutical composition of claim 33, wherein the sterol is at least one selected from the group consisting of: campesterol, sitosterol, stigmasterol, and cholesterol.
35. The pharmaceutical composition of claim 33, wherein the sterol sulfate is according to formula 1:
[ formula 1]
36. The pharmaceutical composition of claim 33, wherein the sterol sulfatase inhibitor is according to formula 2:
[ formula 2]
37. The pharmaceutical composition of claim 33, wherein the bone-related disease is at least one selected from the group consisting of: osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrodysplasia, paget's disease, hypercalcemia, bone tumor destruction, cancer-related bone resorption diseases, bone fractures, osteolysis, osteoarthritis and rheumatoid arthritis.
38. The pharmaceutical composition according to claim 33, wherein the bone-related disease is a climacteric bone disease, and the bone disease is at least one selected from the group consisting of: osteoporosis type I due to menopause, osteoporosis type I due to ovariectomy, spinal stenosis, spinal compression fracture, and osteoarthritis.
39. A method for preventing or treating a bone-related disease, comprising:
sterol sulfate is administered.
40. A method for promoting bone regeneration, comprising:
sterol sulfate is administered.
41. A method for preventing or treating a climacteric disorder, comprising:
a sterol sulfatase inhibitor is administered.
42. A method for preventing or treating a bone-related disease, comprising:
sterol sulfate and sterol sulfatase inhibitors are administered.
[ technical field ] A method for producing a semiconductor device
The present invention relates to a pharmaceutical composition for preventing or treating bone-related diseases.
[ background of the invention ]
Osteoporosis is a typical bone-related disease caused by imbalance in regulation of bone homeostasis between osteoclasts, which are resorbed by bone, and osteoblasts, which form bone, and refers to a bone disease characterized by weakened bone strength, which may lead to an increased risk of fracture (defined by National Institute of Health (NIH), 2000).
Imbalance in regulation of bone homeostasis may be caused by aging, systemic diseases, menopause, etc., and corresponds to a systemic disease in which bone density is decreased and the microstructure of bone tissue is degraded, resulting in an increased risk of bone fracture. In other words, bone density is maintained while a balance is maintained between old bone destruction and new bone formation. However, if replacement of new bone is not successfully completed due to aging, menopause, or the like, the bone becomes loose. As this process occurs repeatedly, the bone thins, resulting in an increased risk of bone fracture or fracture.
In particular, menopause refers to the phenomenon in which ovulation and estrogen production no longer occur due to the decreased ovarian function. It is well known that menopause is a phenomenon that occurs after
Osteoporosis is a disease in which the amount of bone (i.e., bone density) required to maintain normal activities is reduced, for example, due to a decrease in bone calcium content, and thus even a slight impact easily causes fracture. The state before osteoporosis is called osteopenia, which is a state until a hole is generated by gradual thinning and lightening of bone thickness or the like. In addition, osteomalacia refers to a condition in which calcium does not mix with bone in the case of vitamin D deficiency or in the case of kidney disease with large calcium excretion and thus bone is bent in the stage of cartilage formation. In addition, bone atrophy refers to a condition caused by degenerative reduction of bone (i.e., reduction in the amount of bone mass of bone tissue that has been completed).
Since the amount of bone in the human body is maintained by regulating the bone homeostasis achieved by the balance between osteocytes and osteoclasts, it is important to develop a therapeutic agent against molecules that play an important role in these cells. That is, in the case where the activity of osteoblasts forming bone is decreased and the activity of osteoclasts resorbing bone is increased, the destruction of bone is promoted, resulting in diseases such as osteoporosis (in which bone becomes thin and easily breaks); thus, proteins that modulate osteoblast and osteoclast activity are being investigated as therapeutic agents for Bone diseases (Gregory R. Mundy, Journal of Bone and Mineral Metabolism (1996)14: 59-64; Chad Deal, Natural clinical practice RHEUMATOLOGY (2009)), Vol.5, No. 1; kalervo Vaananen, Advanced Drug Delivery Reviews (Advanced Drug Delivery Reviews)57(2005) 959-. However, the currently available drugs for treating osteoporosis are mainly drugs that inhibit osteoclast activity, in addition to parathyroid hormone, and thus the development of drugs targeting osteoblasts is urgently required.
Meanwhile, cholesterol sulfate (corresponding to sterol sulfate) is one of the constituents constituting cell membranes, and is present at high concentration in blood, skin, and the like. However, as for cholesterol sulfate, only a part of functions related to immune function and differentiation into skin cells have been identified so far, and there is no clear report on its in vivo effect.
[ detailed description of the invention ]
[ problem ] to provide a method for producing a semiconductor device
The present invention has been made in order to solve the above-mentioned conventional problems, and provides a pharmaceutical composition or a food composition for preventing or treating bone-related diseases, which comprises sterol sulfate (sterolsulphane) as an active ingredient.
For the purpose of preventing or treating bone-related diseases, the present invention proposes a method for further supplementing sterol sulfate or for inhibiting the decomposition of sterol sulfate, thereby allowing a high sterol sulfate concentration to be maintained in vivo. For a method for further supplementation of sterol sulfate, a compound of
However, the technical problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood from the following description by those skilled in the art. .
[ technical solution ] A
Various embodiments described herein are described below with reference to the drawings. In the following description, numerous specific details are set forth, such as specific configurations, compositions, and methods, in order to provide a thorough understanding of the present invention. However, certain embodiments may be practiced without one or more of these specific details or in combination with other known methods and configurations. In other instances, well-known methods and preparation techniques have not been described in particular detail in order to not unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, composition, or characteristic described in connection with the embodiment is included in one or more embodiments of the present invention. Thus, the appearances of the phrase "in one embodiment" or "in an implementation" in various places throughout this specification are not necessarily all referring to the same embodiment of the invention. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments.
In view of the fact that there has been no report on a drug which simultaneously exerts an effect of increasing bone formation by osteoblasts and inhibiting bone resorption by osteoclasts, the present inventors have conducted repeated studies on such a compound. As a result, the present inventors have found that sterol sulfate esters, particularly [ (3S,8S,9S,10R,13R,14S,17R) -10, 13-dimethyl-17- [ (2R) -6-methylheptan-2-yl ] -2,3,4,7,8,9,11,12,14,15,16, 17-dodecahydro-1H-cyclopenten [ a ] phenanthren-3-yl ] hydrogen sulfate, exhibit a significant effect on the treatment and prevention of bone-related diseases by a method of regulating bone homeostasis, and thus have completed the present invention.
In one embodiment of the present invention, there is provided a pharmaceutical composition for preventing or treating bone-related diseases, which comprises sterol sulfate as an active ingredient.
In the present invention, sterol (sterol) is an abbreviation of steroidal alcohol (steroid alcohol) and refers to an organic molecule of a steroid compound. Sterols are reported to be present in most plants, animals and fungi and can play important physiological functions in eukaryotes, such as constituting the membrane of animal cells or affecting their fluidity, and functioning as secondary signal transducers. For the purposes of the present invention, the sterols may include: the sulfates of campesterol, which is a phytosterol, sitosterol, stigmasterol, and cholesterol, which is an zoosterol. The sterol sulfate (sterol sulfate) is preferably cholesterol sulfate, which may be, but is not limited to [ (3S,8S,9S,10R,13R,14S,17R) -10, 13-dimethyl-17- [ (2R) -6-methylheptan-2-yl ] -2,3,4,7,8,9,11,12,14,15,16, 17-dodecahydro-1H-cyclopentene [ a ] phenanthren-3-yl ] hydrogen sulfate, represented by formula 1:
[ formula 1]
In another embodiment of the present invention, there is provided a pharmaceutical composition for preventing or treating bone-related diseases, comprising [ (3S,8S,9S,10R,13R,14S,17R) -10, 13-dimethyl-17- [ (2R) -6-methylheptan-2-yl ] -2,3,4,7,8,9,11,12,14,15,16, 17-dodecahydro-1H-cyclopenten [ a ] phenanthren-3-yl ] hydrogen sulfate as an active ingredient.
Here, in the present invention, the compound represented by
In the present invention, the bone-related disease may be caused by a dysregulation in activity between osteoblasts, which play a role in generating bone, in vivo and osteoclasts, which play a role in destroying bone, in vivo.
In the present invention, osteoclasts are large multinucleated cells that destroy or resorb bone tissue that is not necessary for the bone growth process. Mature osteoclasts are multinucleated cells that originate from and differentiate from hematopoietic stem cells. In addition, osteoblasts differentiated from mesenchymal stem cells may survive for about 34 months and form new bone at a site where activated osteoclasts break down old bone. Bone formation is accomplished by the process of many osteoblasts forming a bone matrix and mineralizing the matrix. After such bone formation is completed, about 70% or more of osteoblasts die, some of which survive by differentiating into osteocytes and osteocytes. However, in the case of such steady state sustained imbalance, bone-related diseases may occur.
Therefore, for the purpose of the present invention, unlike previously reported pharmaceutical compositions for bone-related diseases, pharmaceutical compositions comprising sterol sulfate as an active ingredient can simultaneously play roles in promoting differentiation into osteoblasts and inhibiting differentiation into osteoclasts and functions thereof. Therefore, the pharmaceutical composition is more effective in treating bone-related diseases.
In particular, in the present invention, the bone-related disease may be at least one selected from the group consisting of: osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrodysplasia (fibrodysplasia), Paget's disease, hypercalcemia, bone tumor destruction (bone), cancer-related bone resorption diseases, bone fractures, osteolysis, osteoarthritis, and rheumatoid arthritis.
Here, in the present invention, the osteoporosis may be at least one selected from the group consisting of: primary osteoporosis due to aging, primary osteoporosis due to menopause (menopause), primary osteoporosis due to ovariectomy, and primary osteoporosis due to orchiectomy. Further, the osteoporosis may be at least one selected from the group consisting of: glucocorticoid-induced osteoporosis, hyperthyroidism-associated osteoporosis, fixed-position osteoporosis, heparin-induced osteoporosis, immunosuppression-induced osteoporosis, renal insufficiency-induced osteoporosis, inflammatory osteoporosis, Cushing's syndrome-induced osteoporosis, rheumatoid osteoporosis, and estrogen synthesis inhibitor-induced osteoporosis.
In addition, the present invention provides a pharmaceutical composition for preventing or treating climacteric symptoms, which comprises the compound represented by
[ formula 2]
In one embodiment of the invention, the compound of
Meanwhile, cholesterol sulfate is one of the constituents constituting cell membranes, and is present at high concentration in blood, skin, and the like. However, to date, only some of their functions related to immune function and skin cell differentiation have been identified for cholesterol sulfate.
In one embodiment of the present invention, the climacteric disorder is a climacteric bone disorder, and the bone disorder may be at least one selected from the group consisting of: osteoporosis type I due to menopause, osteoporosis type I due to ovariectomy, spinal stenosis, spinal compression fracture, and osteoarthritis.
In particular, osteoporosis is a typical bone-related disease, and is a disease in which bone density is reduced due to imbalance in regulation of bone homeostasis between osteoblasts forming bone and osteoclasts absorbing bone; osteoporosis is a bone disease characterized by a reduction in bone strength, which may lead to an increased risk of fracture.
In general, imbalance in regulation of bone homeostasis may be caused by aging, systemic diseases, menopause, etc., and corresponds to a systemic disease in which the bone density is decreased and the microstructure of bone tissues is degraded, resulting in an increased risk of fracture. In other words, bone density is maintained while a balance is maintained between old bone destruction and new bone formation. However, in the case where a new bone replacement cannot be obtained smoothly for various reasons, the bone becomes loose. As this process occurs repeatedly, the bone thins, resulting in an increased risk of bone fracture or fracture.
According to the american society of orthopedics, osteoporosis is classified according to its etiology as primary osteoporosis, which occurs in adults without other systemic diseases that may cause osteoporosis, and secondary osteoporosis associated with other apparent etiologic diseases. Primary osteoporosis is further classified into post-menopausal osteoporosis (type I osteoporosis), age-related osteoporosis or senile osteoporosis (type II osteoporosis), idiopathic osteoporosis, etc. (american orthopedists' society "adult osteoporosis/Bone health is the focus of national public health (steporosis/Bone health as a national public health)" standing statement 1113 (2015)).
In particular, type I osteoporosis may occur even in young female patients under 40 years of age due to early menopause; and in the case of this early menopause, the bone density of these patients is markedly reduced compared with patients with normal menopause after the age of 50 (Shuster, Lynne T. et al, "Premature menopause or early menopause: Long-term health consequences)" menopause (Maturitas)65.2 (2010): 161-166).
In one embodiment of the invention, the composition according to the invention can elevate the volume of trabecular bone. Trabecular bone refers to tissue having a spongy cellular structure and constituting the inner layer of bone.
In type I osteoporosis, in particular, a decrease in bone density is caused by a decrease in hormones such as estrogen and androgen after menopause, an increase in bone turnover, and bone resorption over bone formation. Type I osteoporosis is characterized by relatively greater loss observed in trabecular bone than in cortical bone. In contrast, type II osteoporosis is associated with a gradual decrease in bone density with age in men and women, and its main cause is a decrease in stem cells for bone formation. Osteoporosis type II is characterized by The observation of loss primarily in cortical bone (Dobbs, Matthew B., Joseph Buckwalter and Charles Saltzman, "Osteoporosis: orthopedists's increasing role (osteoporotosis: The creating role of The orthopaedics)" journal of Iowa orthopaedics 19 (1999): 43).
In one embodiment, the pharmaceutical composition according to the present invention provides a pharmaceutical composition for preventing or treating climacteric disorders, wherein the pharmaceutical composition promotes differentiation of preosteoblasts (preosteoblasts) into osteoblasts.
Further, in one embodiment of the present invention, the pharmaceutical composition according to the present invention provides a pharmaceutical composition for preventing or treating a climacteric disorder, wherein the pharmaceutical composition inhibits differentiation of bone marrow cells into osteoclasts.
In the present invention, the climacteric bone-related diseases may be caused by a dysregulation in activity between osteoblasts, which play a role in generating bone in vivo, and osteoclasts, which play a role in destroying bone in vivo.
In the present invention, osteoclasts are large multinucleated cells that destroy or resorb bone tissue that is not necessary for the bone growth process. Mature osteoclasts are multinucleated cells that originate from and differentiate from hematopoietic stem cells. In addition, osteoblasts differentiated from mesenchymal stem cells may survive for about 34 months and form new bone at a site where activated osteoclasts break down old bone. Bone formation is accomplished by the process of many osteoblasts forming a bone matrix and mineralizing the matrix. After such bone formation is completed, about 70% or more of osteoblasts die, some of which survive by differentiating into osteocytes and osteocytes. However, in the case of such steady state sustained imbalance, bone-related diseases may occur.
The pharmaceutical composition according to the present invention can not only increase the volume of trabecular bone, but also simultaneously play roles and functions of promoting differentiation into osteoblasts and inhibiting differentiation into osteoclasts. Therefore, the pharmaceutical composition is more effective in the treatment of climacteric disorders, especially climacteric bone disorders.
Meanwhile, in the present invention, "prevention" may include, but is not limited to, any act of blocking symptoms caused by bone-related diseases, blocking symptoms caused by climacteric diseases, or suppressing or delaying symptoms using the pharmaceutical composition of the present invention.
In addition, in the present invention, "treatment" may include, but is not limited to, any action of using the pharmaceutical composition of the present invention to improve or beneficially modify symptoms caused by bone-related diseases or symptoms caused by climacteric disorders.
In the present invention, the pharmaceutical composition may be in the form of a capsule, a tablet, a granule, an injection, an ointment, a powder or a beverage, and the pharmaceutical composition may be for a human.
In the present invention, the pharmaceutical composition can be formulated into oral preparations such as powders, granules, capsules, tablets and aqueous suspensions, external preparations, suppositories and sterile injectable solutions according to a conventional method and used. However, the pharmaceutical composition is not limited thereto. The pharmaceutical compositions of the present invention may also include a pharmaceutically acceptable carrier. As pharmaceutically acceptable carriers, binders, glidants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, flavoring agents (fragance) and the like can be used for oral administration; a mixture which can be used for injection, such as a buffer, a preservative, an analgesic, a solubilizer, an isotonic agent, a stabilizer and the like; bases, excipients, lubricants, preservatives, and the like may be used for topical application. The formulation of the pharmaceutical composition of the present invention can be prepared in various ways by mixing it with a pharmaceutically acceptable carrier as described above. For example, for oral administration, the pharmaceutical compositions may be formulated as tablets, troches (troches), capsules, elixirs, suspensions, syrups, wafers (wafers), and the like. For injections, the pharmaceutical compositions may be formulated in unit-dose ampoules or in multi-dose formulations. Alternatively, the pharmaceutical composition may be formulated as a solution, suspension, tablet, capsule, sustained release formulation, and the like.
Meanwhile, as examples of carriers, diluents or excipients suitable for preparing formulations, lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, and the like can be used. In addition, bulking agent, anticoagulant, lubricant, humectant, aromatic, emulsifier, antiseptic, etc. can be added.
Routes of administration of the pharmaceutical compositions of the present invention include, but are not limited to: oral, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal routes. Oral or parenteral administration is preferred.
As used herein, the term "parenteral" includes: subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intracapsular (intraburst), intrasternal (intrasternal), epidural, intralesional and intracranial injection or infusion techniques. The pharmaceutical compositions of the present invention may also be in the form of suppositories for rectal administration.
The pharmaceutical composition of the present invention may vary based on a variety of factors, including the activity of a certain compound used, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, pharmaceutical composition, and the severity of a certain disease to be prevented or treated. The dosage of the pharmaceutical composition may vary depending on the condition, body weight, severity of disease, pharmaceutical dosage form, administration route and duration of the patient, and may be appropriately selected by those skilled in the art. The pharmaceutical composition may be administered in an amount of 0.0001 to 10g/kg or 0.001 to 10mg/kg per day. Administration may be once a day or multiple times a day. The dosage is not meant to limit the scope of the invention in any way. The pharmaceutical composition according to the present invention may be formulated in the form of a pill, a coated tablet, a capsule, a liquid, a gel, a syrup, a slurry, or a suspension.
In other embodiments of the present invention, there are provided a food composition for preventing or improving bone-related diseases, which comprises the compound represented by
Meanwhile, in the present invention, "improving" may include, but is not limited to, any action of using the food composition of the present invention to improve or beneficially modify symptoms caused by bone-related diseases.
The food composition comprising the compound of the present invention as an active ingredient can be prepared in the form of various foods, for example, beverages, chewing gums, teas, vitamin complexes, powders, granules, tablets, capsules, candies, rice cakes and breads.
In the present invention, when the compound is contained in the food composition, the compound may be added in an amount corresponding to a proportion of 0.1% to 50% of the total weight. However, the amount of the compound is not limited thereto.
In the present invention, in the case where the food composition is prepared in the form of a beverage, there is no particular limitation except that the food composition is contained in a specified ratio. In this case, as with ordinary beverages, various flavors, natural carbohydrates, and the like may be included as additives. Specifically, examples of the natural carbohydrate may include monosaccharides such as glucose, disaccharides such as fructose, polysaccharides such as sucrose, conventional sugars such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. Examples of the flavoring agent may include natural flavoring agents (thaumatin, stevia extracts (e.g., rebaudioside a and glycyrrhizin), etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).
In the present invention, the food composition of the present invention may comprise, in addition to the above ingredients: various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, colorants, pectic acids and salts thereof, alginic acids and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, ethanol, carbonic acid agents used in carbonated beverages, and the like.
In the present invention, the above-mentioned components may be used alone or in combination. Although the proportion of additives does not conform to the essential elements of the present invention, such additives may be selected in the range of 0.1 to about 50 parts by weight per 100 parts by weight of the food composition of the present invention. However, the amount of these additives is not limited thereto.
[ advantageous effects of the invention ]
The pharmaceutical composition and the food composition, each including the compound of
In addition, the pharmaceutical composition and the food composition, each including the compound of
[ description of the drawings ]
Fig. 1 shows results obtained by identifying the degree of mineralized nodule formation of osteoblasts caused by the addition of the compound of
Fig. 2 shows results obtained by identifying the degree of mineralized nodule formation in osteoblasts caused by the addition of the compound of
Fig. 3 shows results obtained by identifying the degree of mineralized nodule formation of osteoblasts caused by the addition of tauroursodeoxycholic acid, deoxycholic acid, or taurocholic acid, according to an embodiment of the present invention.
Fig. 4 shows results obtained by identifying osteoblast differentiation marker gene expression according to an embodiment of the present invention.
Fig. 5 shows results obtained by identifying the degree of differentiation of bone marrow cells into osteoclasts according to an embodiment of the present invention.
Fig. 6 shows results obtained by evaluating the function of osteoclasts according to an embodiment of the present invention.
FIG. 7 shows results obtained by analyzing bone density in an ovariectomized mouse model according to an embodiment of the present invention.
Fig. 8 shows results obtained by identifying the degree of differentiation into osteoblasts according to an embodiment of the present invention.
[ best mode ] for carrying out the invention
It was verified whether the compounds according to the invention significantly promoted osteoblast mineralization nodules. As a result, in the preosteoblasts to which the compound of
In addition, the results of experiments performed in the ovariectomized mouse model showed that the OVX group showed a decrease in trabecular bone volume of about 40% compared to the control group. In contrast, trabecular volume showed a 90% increase in the group orally administered with the compound of
[ embodiments of the invention ]
The details of the present invention will be further described below by way of examples. These examples are only for describing the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention.
Example 1 identification of preventive or therapeutic Effect of the Compound of
- 上一篇：一种医用注射器针头装配设备
- 下一篇：生物活性寡糖的生产