WO2015147559A1

WO2015147559A1 - Composition for promoting growth comprising chaenomeles sinesis as active ingredient

Info

Publication number: WO2015147559A1
Application number: PCT/KR2015/002949
Authority: WO
Inventors: 손원록; 정지훈
Original assignee: (주)솔빛피앤에프
Priority date: 2014-03-28
Filing date: 2015-03-26
Publication date: 2015-10-01
Also published as: KR20150112419A

Abstract

The present invention relates to a growth promotion effect of chaenomeles sinesis, and more specifically to a pharmaceutical composition for promoting growth, a food composition, and a composition for an animal feed comprising chaenomeles sinesis as an active ingredient. The composition of the present invention comprising chaenomeles sinesis as the active ingredient has an advantageous effect of promoting growth of a physeal plate and a long bone, and the composition of the present invention is effective in promoting a growth and a bone-forming of an infant and a juvenile in a growth period, and furthermore the composition of the present invention alone or with a parallel treatment of a growth hormone treatment has an advantageous effect of treating a stature growth.

Description

【Specification】

[Name of invention]

Growth promoting composition containing Chinese quince as an active ingredient

<ι> This application claims the priority of Korean Patent Application No. 10-2014-0036559, filed March 28, 2014, the entirety of which is a reference of the present application.

<2>

The present invention relates to a growth promoting effect of Chinese quince, and more particularly to a pharmaceutical composition for promoting growth, a food composition and a composition for animal feed comprising the Chinese quince as an active ingredient.

<4>

Background Art

<5> Recently, interest in height growth factors has increased due to the westernization of body shape and the increase in average height. If we define growth as a broad concept, it means not only an increase in height but also an increase in the size and function of each organ of the body, but a concept of consultation can mean an increase in height. This increase in kidney is achieved through skeletal metabolism, which involves the synthesis of cartilage tissue, skeletal length growth, and extensive proliferation of skeletal tissue by various factors such as nutrition and growth hormone. Bone (bone) tissue is a specially differentiated connective tissue, which is composed of several types of cells such as mesenchymal cells, chondrocytes, osteoblast osteoclasts, and bone marrow cells. There is a balance between the amount of bone resorption by osteoclasts and the amount of bone formation by osteoblasts. In the growth period, bone growth is greater than the amount of bone resorption by osteoblasts. Will be done.

<6>

The growth piate is a group of horizontally shaped cartilaginous cells located at both ends of the long bone, located between the metaphys is and the epiphysi s. After the growth of chondrocytes, growth of hypertrophy, secretion of extracellular epilepsy, invasion of blood vessels and bone precursor cells and oss ifi cat ion During the process of endochondral oss ifi cat ion where the cartilage is turned into bone, new bone is continuously formed at the end of the bone trunk of the growth plate, thereby lengthening the long bone. Growth plate is castle It is regulated by hormones such as intestinal hormone, insul in- ike growth factor (IGF), thyroid hormone, sex hormone, and glucocorticoids and various cytokines, which eventually become ossified and fuse with surrounding bones ( Shin, Ho-Ho, 2006, Hormone Growth Edition, Korean Society of Pediatric Endocrinology, vol 11, 117-122.

<8>

Meanwhile, as a method for promoting growth, a growth hormone preparation administration method, an irizanov operation method, and a dietary supplement taking method have been used. In particular, growth hormone therapy, which has been used in the past for pathologically sluggish growth, has been applied to growing children and adolescents with normal kidneys as their interest in height growth has recently increased. However, the method of administration of the growth hormone preparation shows an excellent effect in the case of the lack of growth hormone, but the majority of people with normal hormone secretion have various side effects such as positive terminal hypertrophic growth hormone antibody, systemic allergic reaction, hypothyroidism, etc. There is a problem that can be caused. In addition, problems such as excessive duration and cost of growth hormone therapy, cancer, and disturbance of other growth factors have been found. In addition, ilizanov surgery is an operation that is performed after cutting the bone of the leg, and it is difficult to use it for the general public in terms of pain and cost of patients, and growth supplements are mostly scientifically untested. . <10> Therefore, the efficacy of promoting growth is scientifically verified and the development of safe food materials is required.

<1 1>

[Detailed Description of the Invention]

[Technical problem]

The present inventors while studying to develop a food material having an activity that effectively promotes growth without side effects, confirmed the effect of growth plate promotion and iliac bone length increase in experimental animals administered quince and completed the present invention.

<13>

Accordingly, an object of the present invention is to provide a pharmaceutical composition for promoting growth comprising a Chinese quince as an active ingredient.

<15>

Another object of the present invention is to provide a growth promoting food composition comprising a Chinese quince as an active ingredient.

<17> Another object of the present invention to provide a composition for promoting animal feed comprising a Chinese quince as an active ingredient.

<19>

Another object of the present invention is to provide the use of Chinese quince for the production of growth promoters.

<21>

Another object of the present invention is to provide a use of Chinese quince for preparing a food composition for growth promotion.

<23>

Another object of the present invention is to provide a use of Chinese quince for the production of animal feed for growth promotion.

<25>

Another object of the present invention is to provide a method for promoting growth, comprising administering an effective amount of a Chinese quince to an individual in need of growth.

<27>

Technical Solution

In order to achieve the above object, the present invention provides a pharmaceutical composition for growth promotion comprising a Chinese quince as an active ingredient.

<29>

In order to achieve another object of the present invention, the present invention provides a food composition for growth promotion comprising a Chinese quince as an active ingredient.

<31>

In order to achieve another object of the present invention, the present invention provides a composition for promoting animal feed comprising a Chinese quince as an active ingredient.

<33>

In order to achieve another object of the present invention, the present invention provides the use of a Chinese quince tree for the production of growth promoters.

<35>

In order to achieve another object of the present invention, the present invention provides the use of the Chinese quince for producing a food composition for promoting growth.

<37>

In order to achieve another object of the present invention, the present invention provides a feed for promoting animal growth Provided is the use of Chinese quince for manufacturing. In order to achieve another object of the present invention, the present invention provides a method for promoting growth, comprising administering an effective amount of a Chinese quince to an object in need of growth. . Hereinafter, the present invention will be described in detail. The present invention provides a growth promoting composition comprising a Chinese quince as an active ingredient. The quince tree (qui nce t ree, Chaenomeles sinensis ᅳ) is a deciduous tree of the dicotyledonous rosacea rosaceae, which has several aliases such as Cydonia sinensis, Pseudocydonia sinensis, Cydonia sinensis, and Cydonia oblonga. The Chinese quince tree of the present invention is not limited to any part constituting the Chinese quince, but preferably may be one or more selected from the group consisting of fruit leaves, flowers, stems and roots of the Chinese quince, more preferably It can be a quince fruit. The fruit of the Chinese quince tree is mainly called the herbal name Chaenomelis Fructus, 木瓜), the tree family is also called quince, quince, tree fruit, incense, and the corresponding neck, _hairpin , _{iron shell} , etc., specification of the present invention In the above, the above terms may be commonly used. The Chinese quince tree of the present invention can be processed or used as it is or in a form that can be administered to an animal, but is not limited thereto, and may be, for example, a powder, a suspension extract, and the like. It may be extracted by a natural product extraction method of, preferably water, may be extracted with one or more solvents selected from the group consisting of 1 to 6 carbon atoms organic solvent and subcritical or supercritical fluid, Organic solvents include alcohols, acetone, Ether, benzene, chloroform, ethyl acetate, methylene chloride, nucleic acid, cyclohexane, diethyl ether and petroleum ether It may be selected from the group consisting of (petroleum ether). Preferably it can be extracted using water or alcohol having 1 to 6 carbon atoms.

The Chinese quince extract may include a pretreatment process to increase the extraction efficiency, for example, may be used by grinding the Chinese quince with a grinder.

<56>

Extraction temperature of the extract of the present invention is not particularly limited, and may be, for example, 0 ^° C to 15 C C, preferably 80 ^° C to 120 ^° C. Extraction time of the extract of the present invention is not particularly limited depending on the degree of extraction silver, for example may be 10 minutes to 10 days, preferably 30 minutes to 24 hours, more preferably from 1 hour to 6 It can be time.

<58>

Extract of the present invention can be extracted by known natural product extraction method. For example, it can be extracted by 넁 acupuncture extraction, hot water extraction, ultrasonic extraction ᅳ reflux 넁 angle extraction, heating extraction 몌 preferably can be extracted by hot water extraction or reflux 넁 angle extraction method, once to 10 times, preferably The extraction can be repeated two to seven times.

<60>

In addition, a filtration process, a concentration and purification process, a drying process, a freezing process, and a powdering process may be arbitrarily added for ease of treatment, storage, and the like during the preparation of the Chinese quince extract of the present invention.

<62>

The filtration process may be based on a known filtration method, but is not limited thereto. For example, filtration, centrifugation, and separatory funnel using a filtration network or a micro filter may be used.

<64>

The concentration process may be performed by a known concentration method, but is not limited thereto. For example, the concentration process may be concentrated using precipitation concentration, evaporation concentration, reduced pressure concentration, oriental filtration, reverse osmosis, and centrifugation. . In the concentration process, the concentration is preferably 3 to 50% by weight, more preferably 10 to 20% by weight, and most preferably 14 to 16% by weight, based on the amount of solids. Can be enriched with have.

The solids means an active ingredient remaining when all the solvents of the extract are evaporated, and the present invention includes both soluble solids and insoluble solids.

<67>

The drying process may be by a known drying method, but is not limited thereto, and may be, for example, freeze drying, spray drying, or hot air drying.

In addition, the powdering process may be by a known powdering method, but is not limited thereto, for example, it may be powdered by a process such as dextrin inclusion. Preferably, the extract of the present invention may be powdered by the method of hot air drying by adding crystalline salose as an inert excipient. The addition rate of the crystalline cell may be added in a ratio of 1: 1 to 10, based on the solid content weight, preferably 1: 0.1 to 5, and most preferably 1: 0.5 to 2 Can be.

<70>

The most preferred embodiment of the present invention is an extract of the neck family.

The neck and extracts are not limited thereto, and preferably, may be prepared by a hot water extraction method using water as a solvent. The ratio of neck and water during the extraction of hot water is not particularly limited, but water may be added to the neck 3 times to 20 times (increase). Preferably, water can be added 15-19 times (by weight) to the tree to increase the extraction effect.

In one embodiment of the present invention, the Chinese quince extract of the present invention was put into 10L of water and 600g crushed to the size of 20-40 mesh and extracted with hot water twice at 10C C for 2 hours. The hot water extract was left to cool to cool, filtered and concentrated until the solid content was 15% by weight in the pre-softening phase, and the crystalline cells were mixed and dried in the concentrate to prepare neck and extract powder.

<74>

The growth of the present invention refers to an increase in the size and function of each organ of the body, and preferably to increase the size, thickness, density, length, function increase and growth hormone of the tissues of the proliferative bone (bone). More preferably bone length growth.

<76>

The composition of the present invention contains the Chinese quince as an active ingredient, and is effective in promoting bone length growth and growth of growth plate cartilage tissue. This is illustrated well in the specification examples of the present invention.

<80>

<8i> In one embodiment of the present invention, after administering the neck and neck to rats for 10 days, the tibia

The change in length of (t i b i a) was observed. As a result, the length of the tibia was confirmed to be similar to that of the growth hormone administration group.

In another embodiment of the present invention, after administration of the neck and the neck to rats for 10 days, the change of growth plate tissue was observed. As a result, it was confirmed that the lengths of the growth plate prol i ferat ive zone and hyper t rophi c zone were increased to the level similar to that of the growth hormone administration group.

In another embodiment of the present invention, after administration of the neck and the rat for 10 days, the change in the number of activated chondrocytes in the chondrocytes was confirmed by BrdU staining. As a result, it was confirmed that the ratio of BrdU positiv cel l was increased, thereby promoting the proliferation of chondrocytes in the neck and the administration group.

In another embodiment of the present invention, after administering neck and neck for 10 days at ¾ (^), osteocalcin concentration in plasma was measured. As a result, it was confirmed that the concentration of osteocalcin in plasma was increased in neck and administration group. As a result, it was confirmed that the neck and extract increase osteogenic and osteoblast activity.

<85>

Therefore, the present invention provides a pharmaceutical composition for promoting growth comprising a Chinese quince as an active ingredient.

<87>

The pharmaceutical composition according to the present invention may contain the Chinese quince tree of the present invention alone or may further contain one or more pharmaceutically acceptable carriers, excipients or diluents. As used herein, "pharmaceutically acceptable" is a non-toxic composition that, when administered physiologically, does not inhibit the action of the active ingredient and does not normally cause allergic reactions such as gastrointestinal disorders, dizziness or similar reactions. Say.

<89>

Pharmaceutically acceptable carriers may further include, for example, carriers for oral administration or carriers for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. In addition, peptides It may include various drug delivery materials used for oral administration of the formulation. In addition, carriers for parenteral administration may include water, suitable oils, saline, aqueous glucose, glycols, and the like, and may further include stabilizers and preservatives. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutane. The pharmaceutical composition of the present invention may further include a lubricant wetting agent, a sweetener, a flavoring agent, an emulsifier, a suspension agent, and the like in addition to the above components. Other pharmaceutically acceptable carriers and formulations may be referenced in the following literature (Remington's Pharmaceut i cal Sciences, 19th ed., Mack Publ i shing Company, East on, PA, 1995) . The composition of the present invention may be administered to any mammal, including humans. For example, it can be administered orally or parenterally. Parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal topical, sublingual or rectal administration. Can be. The pharmaceutical composition of the present invention may be formulated into a preparation for oral or parenteral administration according to the route of administration as described above.

In the case of preparations for oral administration, the compositions of the present invention may be formulated using methods known in the art as powder granules, tablets, pills, sugar tablets, capsulants, solutions, gels, syrups, slurries, suspensions and the like. Can be. For example, oral formulations can be obtained by tablets or dragees by combining the active ingredient with a solid brother and then grinding it, adding suitable auxiliaries and processing it into a granular mixture. Examples of suitable excipients include sugars and corn starch, wheat starch, rice starch and potato starch, including lactose, textrose, sucrose, solbi, manny, xili, erysri and malty. _Cellulose , gelatin, polyvinylpyridone and the like may be included, including starch | _cells , methyl _cellulose , sodium carboxymethyl _cellulose and hydroxypropyl methyl-cellulose. In some cases, crosslinked polyvinylpyridone, agar, alginic acid or sodium alginate may be added as a disintegrant. Furthermore, the pharmaceutical composition of the present invention may further include an anti-collar, a lubricant wetting agent, a fragrance, an emulsifier and a preservative.

In the case of parenteral preparation, injection, cream, lotion, external ointment oil Formulations, moisturizers, gels, aerosols and nasal inhalants can be formulated by methods known in the art. These formulations are statements that are commonly known prescriptions for all pharmaceutical chemistry.

¾ (Remington's Pharmaceutical Science, 19th ed., Mack Publishing Company, Easton, PA, 1995).

<97>

The total effective amount of the composition of the present invention may be administered to a patient in a single dose and may be administered by a fractionated treatment protocol which is administered for a long time in multiple doses. Can be. The pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the extent of the disease. Preferably the preferred total dose of the pharmaceutical composition of the present invention may be from about 0.01 / ^ to 10,000 mg, most preferably to lOOOOmg per patient body weight per day. However, the dosage of the pharmaceutical composition is determined by the various factors such as the age, weight, health status, sex, severity of the disease, diet and excretion rate, as well as the formulation method, route of administration and frequency of treatment. As such, those of ordinary skill in the art will be able to determine appropriate effective dosages of the compositions of this invention. A pharmaceutical composition according to the present invention is not particularly restricted in its dosage form _i route of administration and method of administration shown by the effect of the present invention.

<99>

The present invention provides a growth promoting food composition comprising a Chinese quince as an active ingredient.

<101>

<102> The food composition of the present invention is a functional food (functional food), nutritional supplements

It includes all forms such as nutritional supplements, health foods and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.

For example, as a health food, the Chinese quince tree of the present invention may be prepared in the form of tea, juice and drink for drinking or granulated, capsulated and powdered. In addition, the Chinese quince tree of the present invention can be prepared in the form of a composition by mixing with a known substance or active ingredient known to have a bone growth promoting effect. For example, the food composition of the present invention may further contain trace minerals, vitamin lipids, sugars and components having known growth promoting activity, etc., in addition to the Chinese quince or Chinese quince extract component. The minerals may contain nutrients necessary for the growing season, such as calcium, iron, Vitamins may include vitamins (ᅳ) vitamin E, vitamin B1, vitamin B2, vitamin B6, etc. Lipids may contain alkoxyglycerol or lecithin, and sugars may contain fructooligosaccharides. have.

<104>

In addition, functional foods include beverages (including alcoholic beverages), fruits and processed foods (female 1: canned fruit, canned jam, mamalade, etc.), fish, meat and processed foods (eg ham). Sausages and corn, etc.), breads and noodles (e.g. udon noodles, soba noodles, ramen noodles, spaghetti, macaroni, etc.), fruit juices, cookies, sweets, dairy products (e.g. butter, cheese, etc.) It can be prepared by adding the Chinese quince tree of the present invention to vegetable protein, retort food, copper food, various seasonings (e.g., miso, soy sauce, sauce, etc.).

In addition, in order to use the Chinese quince tree of the present invention in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate.

<107>

The content of the Chinese quince in the food composition of the present invention may be contained in a ratio of 0.0190%, preferably 0.150%, based on the total weight of the food based on the total weight of the food composition.

<109>

The present invention is a composition for promoting animal growth comprising a Chinese quince as an active ingredient.

Provide water.

<111>

The feed composition according to the present invention may be prepared in the form of fermented feed, blended feed, pellet form, and silage. The fermented feed includes the Chinese quince tree of the present invention, and may be prepared by fermenting an organic material by adding various microorganisms or enzymes. The blended feed may be prepared by mixing various kinds of general feed and the quince tree of the present invention. Pellet-type feed may be prepared by formulating the fermented feed or blended feed into a pellet machine. Silage can be prepared by mixing fertilizer feed and the Chinese quince tree of the present invention to ferment with lactic acid bacteria.

<113>

The present invention provides the use of Chinese quince for the production of growth promoters.

In addition, the present invention provides a use of the Chinese quince for producing a food composition for promoting growth.

In addition, the present invention provides the use of Chinese quince for the production of animal feed for growth promotion. Ball.

In addition, the present invention provides a method for promoting growth, comprising administering an effective amount of a Chinese quince to an individual in need of growth.

<1 18>

<1 19> The growth of the present invention means an increase in the size and function of each organ of the body, preferably the size, thickness, density, length of tissues of the proliferative bone (bone) increased function and growth hormone More preferably, it means the length of bone growth.

<120>

The Chinese quince represents one or more selected from the group consisting of fruit, leaves, flowers, stems, and roots, and may be processed and used as it is or in form that can be administered to animals. Although not limited thereto, the form that can be administered to the animal may be powder _L suspension suspension, etc., preferably may be a Chinese quince extract.

<122>

The Chinese quince extract may be extracted by a known natural product extraction method, preferably extracted with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, and subcritical or supercritical euse. The organic solvent having 1 to 6 carbon atoms may be 1 to 6 carbon atoms (al cohol), acetone (acetone), ether (ether), benzene (chloroform) chloroform, ethyl acetate (ethyl acetate) It may be selected from the group consisting of methylene chloride (methylene chloride), hexane (hexane), cyclonucleic acid (cyc l ohexane), diethyl ether and petroleum ether. Preferably it can be extracted using water or alcohol having 1 to 6 carbon atoms.

<124>

A pharmaceutical composition comprising the Chinese quince tree as an active ingredient may be administered in various amounts, including oral, transdermal, subcutaneous, intravenous or intramuscular. As used herein, the term "effective amount" refers to an amount indicating bone growth when administered to an individual, and the term "subj ect" may be an animal, preferably a mammal, particularly an animal including a human. The subject may be a growth patient in need of bone growth.

<126>

The Chinese quince extract of the present invention may be administered as it is, or prepared and administered in various formulations as described above, and preferably, may be administered until a desired effect, that is, a growth effect, is derived. Chinese quince tree of the present invention as an active ingredient Including pharmaceutical compositions can be administered by a variety of routes according to methods known in the art. That is orally or parenterally, such as oral, intramuscular, intravenous, intradermal, intraarterial, intramedullary, intradural, intraperitoneal, intranasal, intravaginal, rectal, sublingual or subcutaneous, or into the gastrointestinal tract, mucosa or respiratory tract. Can be administered ᅳ [Effective Effect]

The composition comprising the Chinese quince tree as an active ingredient has an effect of promoting growth of growth plates and long bones, and is effective in promoting growth and skeletal formation of infants and adolescents during the growing season. As well as the composition of the present invention alone or in combination with growth hormone treatment is effective for the treatment of height growth.

[Brief Description of Drawings]

1 is a diagram showing the change in weight of rats (rat) for 10 days for each administration group.

Figure 2 shows the results of micro-CT imaging of rat tibia (tibia) for each administration group. Figure 3 shows the X-ray image of the rat tibia for each administration group.

Figure 4 shows the total tibia length of the rat for each administration group (total tibia length).

Figure 5 shows the location and relative length of the proliferative zone and hypertrophic zone in the growth plate of the rat for each administration group (control: saline administration group, GH: growth hormone administration group, neck and neck: neck and extract administration group) .

6 is a diagram showing the length of the proliferation zone (prol i ferative zone) in the growth plate (growth plate) area of each administration group (control: saline administration group, growth: growth hormone administration group, neck: neck and extract administration group).

Figure 7 is a diagram showing the length of the hypertrophic zone of the growth plate (growth plate) area of each administration group (control: saline administration group, growth: growth hormone administration group, neck and neck: neck and extract administration group).

Figure 8 shows the results of BrdU staining the cartilage tissue of each administration group as an image.

Figure 9 shows the ratio of BrdU positive cells in the cartilage tissue of each administration group. Figure 10 shows the results of measuring the concentration of osteocalcin (osteocalcin) in the plasma in each administration group. <141>

[Form for implementation of invention]

Hereinafter, the present invention will be described in detail.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

<144>

<145> <Example 1>

<146> Preparation of Chinese Quince Extract

<147> The tree was purchased from Dongyang Pharmaceutical Co., Ltd.

Using 50L extractor (Pressure extractor, Korea Industrial Co., Ltd.), add crushed neck, 600g (dry weight), and 10L of water into 20 ~ 40mesh, and extract hot water twice at lOCTC for 2 hours. The hot water extract is left at room temperature, cooled to room temperature and filtered. The filtered extract was concentrated with 20 L evaporator (Rotory Evaporator, HEID0LPH) until the solid content became 15% by weight (solid content 33.27 g of the solid solution before the pre-mixed solution) to prepare a concentrate. After mixing the crystalline cells of the same weight as the solids in the concentrate, and dried for 2 days (i (xrc hot air drying)) in a dryer to obtain the remaining 66.79g of the neck and extract powder after evaporation of all moisture.

<148>

<149> <Experimental Example 1>

<150> Investigation of Growth Promotion Effect of Chinese Quince Extract Using Animal Model

<151>

<1-1> Administration of Extract of the Chinese Quince (Thursaceae)

Three-week-old Male Sprague-Daw ley rats were purchased and stabilized for three days. The breeding environment was maintained at 24 ^° C 2 ^° C, and the light and dark cycles were kept for 12 hours, and the feed was used as a general solid feed without antibiotics. The control group was infused with sal ine, and the oral and extracts were orally administered once daily by oral administration (the neck and extract powder prepared in Example 1 was dissolved in water and administered). In the Positiv group, Eutropin (LG Life Sciences) was injected subcutaneously once daily at a dose of 20 / g / kg. In the neck and extract administration method of the present invention, rats are administered to oral cavi ty in all groups except the posi ive group, and all animals are administered once daily. The composition of each group is as follows.

<154>-Control administration group ^' Normal sal ine lml

<155> 一 Posi t ive Control ： growth hormone, 20 ig / kg

Neck and administration group 200 mg / kg <157>

<158> After 10 days of ingestion of feed and neck and extracts, an autopsy confirms the following.

<159>

<160> <1-2> Weight Change of Experimental Animal

The weight of each group of Experimental Example <1-1> before dietary administration and after dietary administration for 10 days was measured. The measurement was performed twice a week. The measured values were statistically calculated to calculate the mean and standard deviation.

<162>

As shown in FIG. 1, 10 days of observation showed that there was almost no difference in weight in the control group, the experimental group, and the growth hormone administration group. This indicates that the mouse 'weight is not significantly correlated with the effect of neck and dosing.

<164>

<165>

<166> * <1-3> Assessment of Osteoporosi s Toxicity in Bone Abnormal Proliferation and Osteoporosis

In the experimental group and the control group ingested the Chinese quince or radish extract according to the present invention after the administration for 10 days in the Experimental Example <1-1>, overgrowth of bone or osteoporosis

The presence or absence of (osteoporosi s) was evaluated by the micro-CT method.

The volume and thickness of the trabecular bone associated with the bone density of the left tibia were confirmed by micro-CT examination. In the state where the left tibia was extracted by lethal rats, the volume and the thickness of the trabecular bone were measured using micro-CT. Mi cro— CT system uses SKYSCAN 1172 mi cro-CT device and X-ray source is 50kV, 200mA. The source and detector are fixed and the object rotates between them to obtain projection data. The image has a size of 0.8um-25um pixels. Use a micro-CT to scan the entire F0V (Field of view) of the left tibia neck and a partial F0V scan of the region of interest (R0I) to determine the correct rat ios (Chunet al 2004). The ratio and thickness of trabeculae are calculated by reconstructing the volume ratio of trabecula (BV / TV,%) and bone thickness (Tb.Th, mm) inside the rectangle of the left femur in the 2D image. The fuzzy di stance transform (FDT) algorithm was applied (In Kon Chunl., Et al., In vivo trabecular thickness measurement in cancel lous bones: longi tudinal rat imaging studies. Phys iol. Meas. 27 (2006) ) 695-702) <169>

Micro—Percentage bone volume, trabecular separation, and trabecular thickness as viewed through CT are mainly used as indicators for osteoporosis and bone abnormality. As shown in FIG. 2 and Table 1, there is almost no difference between the groups, and it can be seen that these drugs do not affect the abnormal growth of bone or osteoporosis toxicity during the experimental period.

<171>

<172> [Table 1]

<173>

<174>

<i75> <l-4> Measurement of tibia length changes in experimental animals

After the administration for 10 days in the Experimental Example <1-1> is completed, the left and right tibia (shalp bone) of the experimental group and the control group ingested the Chinese quince or radish extract according to the present invention is attached to the bone tissue All muscles, fats, ligaments, etc. were removed and stored in 70% alcohol and X-ray equipment (0M-F0RTE -10121 ᅳ DK Medical System) was used. X-ray source was 55kV, 320mA. Tibia length was measured by X-ray imaging of the tibia.

<177>

As shown in FIG. 3 and FIG. 4, growth hormones were increased compared to the control group.

The total tibia length was increased in the other groups, and the total tibia length was also increased in the group treated with the neck compared to the control group.

<179>

<180> <1-5> Measurement of Growth Plate Cartilage Change in Experimental Animals

<i8i> The length of the growth plate zone is fixed by cartilage tissue after autopsy and stained by H & E staining technique, followed by microscopy. Measure the length of each zone 5 times per sample and use the averaged value as a representative value to evaluate the significance. <182>

As shown in FIG. 5 to FIG. 5, the proliferative and hypertrophic zones of the growth hormone-administered group were increased compared to the control group, and the proliferative and hypertrophic zones of the neck and administration groups were also increased. The length increased significantly compared to the control group.

<184>

<185> <1-6> Chondrocyte proliferation effect

In order to measure the degree of chondrocyte proliferation, rat tibial cartilage tissue was used and brdU staining was applied to S phase proliferative cells in the growth plate of this region. Sigma 5-Bromo-2-deoxyur idine (Product No .: B9285) was dissolved in ammonium hydroxide (NH ₄ 0H) 0.1M at a dose of 30 mg / kg and intraperitoneally administered 1 hour prior to the end of the experiment. Paraffin embedded tissues were fixed and stained by BrdU staining kit (Invitrogen, 93-3943). BrdU positive ceH was counted using a cell counter.

<187>

As a result, as shown in FIGS. 8 and 9, the growth rate of BrdU positive cells was increased to a similar level in both the growth hormone group and the neck and administration groups compared to the control group. This indicates that the neck and the administration group have a chondrocyte proliferation effect.

<189>

<190> <1-7> Osteoblast Activator Plasma Osteocalcin Measurement

<i9i> Rat blood was collected from the heart after administration and uncoated, and serum was isolated to make a sample. Rat Ostecalcin / Bone Gla Protein. Total osteocalcin levels in serum were measured using the OT / BGP EL ISA Kit (Cusabio, product number: CSB—E05129r).

<192>

As a result, as shown in FIG. 1, it was confirmed that the plasma osteocalcin level was significantly increased in both the growth hormone administration group and the neck and extract administration group compared with the control group. In particular, the results of slightly higher levels of osteocalcin were found in the neck and administration groups compared to the growth hormone administration group. Osteocalcin is formed in osteoblasts and then deposited in the bone matrix, and some of the newly formed osteocalcin is released into the blood. Therefore, the level of bone formation can be determined by measuring blood levels. Concentrations are believed to reflect the activity of osteoblasts. It has been shown that the neck and extract of the present invention significantly increase the concentration of osteocalcin in plasma, resulting in increased bone formation and osteoblast activity.

<194>

Industrial Applicability

As described above, the present invention relates to a growth promoting effect of a Chinese quince, and more particularly to a pharmaceutical composition for promoting growth, a food composition and a composition for animal feed comprising the Chinese quince as an active ingredient. will be.

The composition comprising the Chinese quince of the present invention as an active ingredient has an effect of promoting growth of growth plates and iliac bone, and is effective in promoting growth and skeletal formation of infants and adolescents during the growing season, as well as the composition of the present invention. It is highly industrially available because it is effective for the treatment of height growth, either through or in combination with growth hormone therapy.

Claims

【Scope of Claim】

【Claim 1】

A pharmaceutical composition for growth promotion containing quince as an active ingredient.

【Claim 2】

A food composition for growth promotion containing quince as an active ingredient.

【Claim 3】

A composition for animal feed for growth promotion containing quince as an active ingredient.

【Claim 4】

The composition for promoting growth according to any one of paragraphs 1 to 3, wherein the quince tree is one or more selected from the group consisting of fruits, leaves, flowers, stems, and roots of the quince tree.

【Claim 5】

The composition for growth promotion according to any one of paragraphs U to 4, wherein the quince tree is a quince tree extract.

【Claim 6】

According to claim 5, the quince tree extract is water, alcohol with 1 to 6 carbon atoms, acetone, ether, chloroform, ethyl acetate, methylene chloride, nucleic acid, cyclonucleic acid, petroleum ether, diethyl ether, benzene, and A composition for promoting growth, characterized in that it is an extract using at least one solvent selected from the group consisting of subcritical or supercritical fluids.

【Claim 7】

The composition for promoting growth according to any one of claims 1 to 6, wherein the growth is bone growth.

【Claim 8】

Use of quince tree for manufacturing growth promoters.

[Claim 9]

Use of quince tree for manufacturing food compositions for growth promotion.

【Claim 10】

Use of quince tree to manufacture growth-promoting animal feed.

【Claim 11】

The use of the quince tree according to any one of claims 8 to 10, wherein the quince tree is one or more selected from the group consisting of fruits, leaves, flowers, stems and roots of the quince tree.

[Claim 12]

The use of the quince tree according to any one of paragraphs 8 to 11, wherein the quince tree is a quince extract.

[Claim 13]

The method of claim 12, wherein the quince tree extract is water, alcohol having 1 to 6 carbon atoms, acetone, ether, chloroform, ethyl acetate, methylene chloride, nucleic acid, cyclonucleic acid, petroleum ether (petrol eum ether), and diethyl ether. ， Use of quince tree, characterized in that it is an extract by one or more solvents selected from the group consisting of benzene and subcritical or supercritical fluid.

[Claim 14]

11. Use of quince according to any one of claims 8 to 10, wherein the growth is bone growth.

【Claim 15】

A growth promotion method comprising administering an effective amount of quince to an individual in need of growth.

[Claim 16] The method of claim 15, wherein the quince tree is one or more selected from the group consisting of fruits, leaves, flowers, stems and roots of quince trees.

[Claim 17]

The method of claim 15, wherein the quince tree is a quince extract.

[Claim 18]

The method of claim 17, wherein the quince tree extract contains water, an alcohol having 1 to 6 carbon atoms _, acetone, ether, chloroform, ethyl acetate, methylene chloride, nucleic acid, cyclohexane, petroleum ether, diethyl ether, A method for promoting growth, characterized in that the extraction is performed using at least one solvent selected from the group consisting of benzene and subcritical or supercritical fluids.

[Claim 19]

19. The method of any one of claims 16 to 18, wherein the growth is bone growth.