KR20160001392A - Composition comprising the combined extracts of Phlomis umbrosa, Astragalus membranceus, Discorea japonica, Acanthpanax senticosus and Angelica gigas for stimulating bone growth - Google Patents

Abstract

Provided is a composition for promoting longitudinal bone growth, which contains a composite extract of Phlomis umbrosa Turczaninow, Astragalus membranaceus BUNGE, Dioscorea batatas DECNE, Acanthopanax senticosus (RUPR. et MAX.) HARMS, and Angelica gigas Nakai. The composition of the present invention exhibits effects of promoting longitudinal bone growth.

Description

The present invention relates to a composition for promoting growth of bone length, which comprises a complex extract of Angelica keiskei koidz., Acanthopanax senticosus, Acanthopanax senticosus, Angelica gigas Nakai, and Angelica gigantosa as active ingredients (Composition comprises the combined extracts of Phlomis umbrosa, Astragalus membranceus, Discorea japonica, Acanthpanax senticosus and Angelica gigas for stimulating bone growth }

The present invention relates to a pharmaceutical composition for promoting the growth of bone length, which comprises a complex extract comprising at least one kind of a herbicide, a herbicide, a scabbard, a scabbard, a ginseng root and a ginseng root as an active ingredient.

Further, the present invention relates to a food composition for promoting growth of bone length, which comprises a complex extract comprising at least one component selected from the group consisting of a herbicide, a horseradish, a scab, a scabbard, and a ginseng.

Short stature refers to a case where the height is less than 3% (third from the smallest of 100) in the normal distribution of children of the same age with the same sex. The causes of these short stature can be classified into normal stools with no disease, genetic tendency and constitutionally short stature, and short stature secondary to stool due to disease.

The normal mutation short stature may be again classified as familial short stature, constitutional growth delay, or idiopathic short stature. The familial short stature is genetically small, and the constitutional growth retardation is constitutionally late, and the height is now small but the puberty is late and the growth continues until late and the final adult height reaches the normal range. In addition, idiopathic short stature generally has a mean of -2 standard deviations below average or less than the third percentile, but has no cause to cause short stature, was born with normal weight at birth, (J Korean Pediatrics, Vol. 49, No. 7, 2006). In the present study, we examined the effects of growth hormone supplementation on growth hormone secretion in children.

On the other hand, short stature secondary to disease is divided into primary growth disorder (endogenous disorder) and secondary growth disorder (extrinsic disorder). The primary growth disorders include, but are not limited to, osteochondral dysplasia, short stature due to chromosomal anomalies (Down syndrome or Turner syndrome), unfavorable light weight (delayed in uterine growth), shortening due to Frederick-Willi Syndrome, , Short stature due to the Noon syndrome, and the like. The secondary growth disorders include short stature due to nutritional deficiency, short stature due to chronic system disease, short stature due to growth hormone deficiency, short stature due to hypothyroidism, short stature due to sexual maturity, short stature due to Cushing's syndrome, This can be.

The majority of children who visit a hospital with short stature are short stature that belongs to normal variation. According to foreign studies, 80% of families with familial and constitutional short stature, 10% with growth hormone deficiency, 4% with thyroid dysfunction, 3% with chronic diseases such as chronic renal failure, (1%), bone formation (1%), and mental illness (1%).

Growth hormone, which is mainly used for the treatment of short stature, was initially used only for short stature due to growth hormone deficiency in pediatric patients. However, its use expanded to extend to Turner syndrome, short stature due to chronic kidney failure and adult growth hormone deficiency, (Prader-Willi syndrome), and idiopathic short stature with a kidney of -2.25 SD or less (Kim et al., 2004), the indications for children with idiopathic short stature The effect of growth hormone on the growth of human pituitary dwarf. In Korea, in August 2009, recombinant human growth hormone was approved by the Korea Food and Drug Administration (KFDA) for a new indication for idiopathic short stature in children.

In particular, many children with idiopathic short stature have increased kidney growth after one or two years of growth hormone use but are uncertain as to whether the final adult height is increased. In the first year of growth, the growth rate was 2.86 cm higher than that of untreated children and 5.3 years for growth hormone, according to the Cochrane report. 6 cm larger. There is no consistent conclusion as to whether the final adult height increases as the growth hormone dose increases, until the final adult height is reached, and whether the child with short stature will gain psychological benefit after treatment with growth hormone , Korean J Ped. Vol. 49. No. 7. 2006). In addition, growth hormone administration in idiopathic short stature is an ethical treatment for children with no disease, and it is necessary to use a high dose, and it is expensive for the general public to use growth hormone, resulting in a 2.5 cm increase in final adult height of $ 35,000 . The longer the treatment period, the greater the capacity to grow and the longer the growth hormone, the growth rate is temporarily reduced, and the treatment effect is very different for each individual, there is no indicator to predict who will respond well. It is not easy to determine the use of growth hormone in the absence of long-term observations of future problems with long-term use of high-dose growth hormones (Shin, JH, et al. 7. 2006).

On the other hand, conventional growth hormone injections are scheduled to be subcutaneously injected at home before going to bed every 6 to 7 times a week. Growing children who need to be injected every day suffer physical pain and psychological burden, and there are few hassles and psychological burdens on the part of the guardian who should give injections to their children. In addition, there is a sense of psychological burden of injecting and avoiding the eyes of others outside of the family, and it is difficult to refrigerate and transport injections during travel or long-term outpatient care (Kang, Hye-young et al. Economic evaluation. As a result of the questionnaire survey of the parents of the infants taking the daily injections, the quality of life quality or utility value of the infants was 0.584 (0-100 scale) ) Was 58.4% of the normal quality of life (100 points). The average quality of life was estimated to be 0.784, which is 78.4% of the normal quality of life (Gang, Hye-young et al.). The growth hormone (GH) Economic evaluation. In general, 3% of children receiving growth hormone are known to experience adverse drug reactions. Arthralgia, myalgia, but may be less frequent than adults and may cause fat atrophy at the injection site and temporary gynecomastia. In addition, changes in hormones and metabolites, including thyroid hormones, may occur, and thyroid function tests are performed every 3 to 6 months. In some of the unjustified lightweight children, facial asymmetry may be exacerbated. Elevation of intracranial pressure is well developed in children, especially in Turner syndrome, chronic renal failure, and chronic growth hormone deficiency syndrome. However, when the growth hormone is withdrawn, , Recent advances in growth hormone therapy, Korean J Ped. Vol. 49. No. 7. 2006).

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have published a report on long-term epidemiological studies in patients with "somatropin" injections in the "childhood" to report the risk of mortality in the "somatropin preparation" . An analysis of approximately 7,000 young adults receiving the drug across France showed that the mortality rate for patients who received "somatropin" was about 30% higher than for the general population (the French population) (Food and Drug Administration, 2010).

According to the distribution of population by national age in 2009, about 6 million people aged 5 to 14 years, which is the period of growth treatment, accounted for about 180,000 persons, 3% of whom were short stature. Of the total number of patients with short-term disease. The total number of patients who received the prescription of growth hormone under the support of health insurance was 12,000 in 2012 as of 2009, % Have not been treated for low - stature. Many of the patients with short stature are not treated because of insured growth hormone treatment costs of 250-300,000 won a year, and short stature, which accounts for about 80% of short stature Idiopathic insomnia is not covered 1 year It is estimated that the high cost of 1,000 ~ 15 million won can be an economic burden and also due to the physical pain and psychological burden of the child who should be injected every day.

Growth hormone therapy was proven to be superior to other methods in terms of growth effects, but the combination of various factors such as cost and convenience showed only 29.1% (Huh, Kyung, Park, In this study, we conducted a questionnaire survey of children who visited our clinic. There is a large market demand for the potential market for oral products of low-shortness drugs to be estimated to be over 5 billion dollars (Hanol Pharm, Company Presentation Session, 2009).

On the other hand, under oriental culture, Chinese medicine is very favored for the treatment of diseases and health promotion. As a result of research on parents of children visiting growth clinics, The access to herbal medicine is much higher than the growth hormone, which is 13 times that of the treatment. A survey of parents of 823 children (416 boys and 407 girls) who visited the Sanggye Paik Hospital Growth Clinic from 2006 to 2007 showed that 33.4% of all parents had artificial management to increase their height, Among them, 37.8% of them were using growth-promoting herbal medicines, 37.1% of them were supplements to help them grow, and 2.9% of them received 3.0% growth hormone therapy. , Park Mi-jung, and college hospital growth clinics, Korean Journal of Pediatrics Vol. 52, No. 5, 2009). Most of the prescriptions used in oriental medicine clinics have not been validated for the growth model and there is a lack of pharmacokinetic and pharmacodynamic indexes. For herbal medicine used clinically, firstly, it is necessary to develop a modern science and demonstrate the effectiveness of the growth model at the experimental animal level. Growth hormone treatment was the highest with growth hormone treatment (29.1%), fitness equipment (6.6%), herbal medicine (6.2%) and growth supplement (2.8%) were the lowest among the 823 parents who visited the growth clinic. Growth hormone injections were the most satisfying compared to other methods. The growth effect proved to be superior to other methods in terms of growth. However, only 29.1% of the growth hormone injections were combined with various factors such as cost and convenience. (P <.05). In addition, the results of this study are as follows.

Accordingly, there has been a demand for the development of a preparation derived from a natural product and having an excellent effect of promoting the growth of bone length.

Phlomis umbrosa is a perennial plant belonging to the genus Labiatae. It is distinguished from the Dipsacusar asperium ( Dipsacusarum ). It also helps to strengthen the muscles, communicate the blood vessels, , Premature ejaculation, and anemia.

Astragalus membranceus is a perennial herb that belongs to the leguminosae family. It is a root with almost no peel from the juniper. It contains sucrose, glucoronic acid, various amino acids, acemic, choline, betaine, folic acid, and the like. The efficacy of traditional oriental medicine can be summarized as follows: body weakness, sweating, swelling, stomach pain, abdominal pain, kidney damage, ear ache, Pus), uterine bleeding, menstrual irregularities, unborn childbirth, postpartum nausea, and genital warts. It may be due to the following: (祛痰 软), headache, deepening of the mulching (肺 pulmonary heartburn), dysentery and pediatric diseases are effective.

Dioscorea japonica is a perennial vine plant belonging to the genus Dioscoreaceae and is used as a herbal medicine or a river decoration. It contains a lot of sticky viscous substance called mannose inside the roots of the root. The main ingredient is starch and contains nutrients such as protein, minerals, vitamin C and vitamin B1. It has been used for treating diseases such as stroke, hypertension, women's disease, diabetes, and pulmonary tuberculosis.

Acanthopanax Senticosus has been reported to dry root, rootstock and bark of Zanosaccharomyces japonica ( Acanthopanax senticosus ), a deciduous shrub of Araliaceae, and has been reported to induce sedation, anti-stress, immune enhancement, smooth muscle relaxation and anti- It is known that it has the effect of strengthening the spleen, adding flies, seeing the kidneys, stabilizing the mind, strengthening the waist, and circulating the blood. Therefore, the fatigue and loss of appetite caused by the spleen and lungs are weakened, the pain and fatigue of the back and knee caused by the weakness of the spleen and kidneys, the weakness of the anemia and weakness due to weakness of the heart and spleen, anorexia, insomnia, It has been widely used for the treatment of weakness, various species and rheumatoid arthritis.

Angelica gigas ) are classified as Angelica gigas Nakai, Angelica sinensis (Oliv.) Diels: 中國 當 return and Angelica acutiloba (Sieb. & Zuc.) Kitagawa. Among them, Chinese herbal medicines have been used in blood medicine and hematopoietic system, action on the uterus, cardiovascular system, blood pressure, Systemic action, immune system action, analgesic action, anti-inflammatory action, antibacterial action, liver function protection action, anti-cancer action and hematopoietic action. Ingredients of Chinese angelica are known to be ligustilide, nbutylidenephthalide, vitamin B-12, and folic acid.

Accordingly, the present inventors have conducted extensive research to find solutions to problems such as high cost, low absorption rate, and side effects of growth hormone used for growth promotion. In searching for natural products, the bone length And thus the present invention has been completed.

Korean Patent No. 0851855

It is an object of the present invention to provide a composition excellent in bone-length growth promoting effect.

It is also an object of the present invention to provide a composition which is excellent in the effect of promoting growth of bone length and can be produced at low cost.

The present invention provides a pharmaceutical composition for promoting bone length growth comprising an extract of crude drug complex as an active ingredient.

The present invention also provides a food composition for promoting bone length growth comprising an extract of crude drug complex as an active ingredient.

Hereinafter, the present invention will be described in detail.

Pharmaceutical composition

The present invention provides a pharmaceutical composition for promoting the growth of bone length, which comprises a complex extract comprising a constant velocity, a horsetail, a scab, a scabbard, a ginseng, and Angelica gigantosa as an active ingredient.

In the present invention, it is preferable to use young leaves and roots at the early stage and use roots.

In the present invention, hwanggi can be a leaf, a young shoot or a root, and it is preferable to use a root.

Further, in the present invention, it is preferable to use roots as the scab.

In addition, in the present invention, the leaves may be leaves, stems, roots or fruits, and it is preferable to use stems.

In addition, in the present invention, Angelica gigas can be selected from Angelica gigas Nakai, Chinese Angelica gigas or Angelica gigas. In addition, in the present invention, Angelicae gigas can be used with leaves and roots, and it is preferable to use roots.

According to one embodiment of the present invention, the combined extract of the present invention may be an extract of a mixture of fast speed, hwanggi, acanthopanax senticosus, and Angelica gigantosum.

According to another embodiment of the present invention, the complex extract of the present invention may be a mixture of a fast-speed extract, an acanthopanax extract, a scutellum extract, a cauliflower extract, and a ganoderma extract.

In addition, the complex extract may be extracted from water, alcohol, or a mixed solvent thereof. The alcohol is preferably a C1-C4 lower alcohol, more preferably methanol or ethanol. The extraction method may be, but not limited to, shaking extraction, Soxhlet extraction, or reflux extraction. The extraction temperature is preferably 40 to 100 캜, more preferably 60 to 80 캜. The extraction time is preferably 2 to 24 hours, and the extraction time is preferably 1 to 5 times.

In the present invention, it is possible to mix at a weight ratio of 1 to 5: 5 to 15: 10 to 100: 5 to 15: 10 to 50, preferably 2: 4: 8: 12: 40 ~ 60: 8 ~ 12: 20 ~ 30, and exhibits the best bone length growth effect in the above range.

The pharmaceutical composition of the present invention has been found to be superior in growth hormone level to bone length, and thus can be used as a pharmaceutical composition for promoting bone length growth.

Further, since the pharmaceutical composition of the present invention has been found to have a bone-length growth effect, it can be used for prevention or treatment of growth disorders.

The growth disorder may be short stature, short stature, or short stature secondary to disease. The normal mutated short stature may be familial short stature, constitutional growth retardation, and idiopathic short stature in agreement. The primary growth disorder may be osteochondral dysplasia, chromosomal aberration (Down syndrome or &lt; RTI ID = 0.0 &gt; Turner syndrome), short stature due to Russell-Silver syndrome, and short stature due to Noonan syndrome. The secondary growth disorders include chronic (chronic) Short stature due to systemic disease, short stature due to growth hormone deficiency, short stature due to hypothyroidism, short stature due to Cushing's syndrome, and psychosocial dwarfism.

Furthermore, since the pharmaceutical composition of the present invention contains herbal ingredients, it can promote bone length growth without side effects.

The complex extract of the present invention is preferably contained in an amount of 0.1 to 50% by weight based on the total weight of the pharmaceutical composition of the present invention. However, the above content is not necessarily limited to this, and may vary depending on the condition of the patient, the type of disease, and the degree of progress of the disease.

In the pharmaceutical composition of the present invention, the complex extract may be administered once or several times in a dose of about 1 mg to 1 g per day, preferably in a dose of 30 mg to 120 mg, Do. However, the dose of the compound extract of the present invention can be appropriately adjusted depending on the condition of the patient such as the severity, age, sex, and weight of the patient and the formulation, administration route and administration period of the drug.

In addition, since the pharmaceutical composition of the present invention has no toxicity and side effects, it can be safely used even when taken for a long time.

The pharmaceutical composition of the present invention may contain additives such as pharmaceutically acceptable diluents, binders, disintegrants, lubricants, pH adjusting agents, antioxidants, solubilizing aids and the like to the extent that the effects of the present invention are not impaired.

The diluent may be sugar, starch, microcrystalline cellulose, lactose (lactose hydrate), glucose, di-mannitol, alginate, alkaline earth metal salt, clay, polyethylene glycol, anhydrous calcium hydrogen phosphate or a mixture thereof.

The binder may be selected from the group consisting of starch, microcrystalline cellulose, highly disperse silica, mannitol, di-mannitol, sucrose, lactose hydrate, polyethylene glycol, polyvinylpyrrolidone (povidone), polyvinylpyrrolidone copolymer , Hydroxypropylcellulose, natural gum, synthetic gum, copovidone, gelatin, or a mixture thereof.

The disintegrant may be a starch or modified starch such as sodium starch glycolate, corn starch, potato starch or pregelatinized starch; Clays such as bentonite, montmorillonite, or veegum; Cellulose such as microcrystalline cellulose, hydroxypropylcellulose or carboxymethylcellulose; Alginates such as sodium alginate and alginic acid; Crosslinked celluloses such as croscarmellose sodium; Guar gum and xanthan gum; Crosslinked polymers such as crosslinked polyvinylpyrrolidone (crospovidone); Sodium bicarbonate, citric acid and the like, or a mixture thereof.

The lubricant may be selected from the group consisting of talc, stearic acid, magnesium stearate, calcium stearate, sodium lauryl sulfate, hydrogenated vegetable oil, sodium benzoate, sodium stearyl fumarate, glyceryl behenate, glyceryl monolate, glyceryl monostearate, Stearate, colloidal silicon dioxide, or a mixture thereof may be used.

The pH adjusting agent may be an acidifying agent such as acetic acid, adipic acid, ascorbic acid, sodium ascorbate, sodium ethoxide, malic acid, succinic acid, tartaric acid, fumaric acid, citric acid (citric acid) and precipitated calcium carbonate, ammonia water, meglumine, Basic agents such as sodium, magnesium oxide, magnesium carbonate, sodium citrate, and tribasic calcium phosphate can be used.

As the antioxidant, dibutylhydroxytoluene, butylated hydroxyanisole, tocopheryl acetate, tocopherol, propyl gallate, sodium hydrogen sulfite, sodium pyrophosphate and the like can be used. In the prior-release compartment of the present invention, Polyoxyethylene sorbitan fatty acid esters such as sodium lauryl sulfate and polysorbate, docusate sodium, poloxamer and the like can be used.

The pharmaceutical composition of the present invention may be formulated into solid preparations such as tablets, pills, powders, granules, capsules and the like for oral administration, and such solid preparations may contain the complex extract and at least one excipient such as starch, calcium For example, calcium carbonate, sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. The pharmaceutical composition may be formulated into liquid preparations such as suspensions, solutions, emulsions and syrups for oral use. In addition to water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, Can be formulated into liquid formulations.

In addition, the pharmaceutical composition of the present invention may contain sterilized aqueous solution, non-aqueous solvent, suspension, emulsion, freeze-dried preparation and suppository for formulation for parenteral administration.

Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The term "administering" in the present invention means introducing the pharmaceutical composition of the present invention to a patient by any suitable method, and the administration route of the pharmaceutical composition of the present invention may be administered through any common route . But are not limited to, oral, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, intranasal, intrapulmonary, rectal, intramuscular, intraperitoneal, intrathecal . For example, by oral, rectal or intravenous, intramuscular, subcutaneous, intramural or intracerebroventricular injection.

The pharmaceutical composition of the present invention may be administered once, or may be administered in several divided doses at regular time intervals.

In addition, the pharmaceutical composition according to the present invention may further include other active ingredients having bone length growth promoting effect.

The pharmaceutical composition according to the present invention may be used alone or in combination with various methods such as hormone therapy and drug therapy to promote bone length growth.

Food composition

The present invention provides a food composition for promoting the growth of bone length, which comprises a complex extract comprising a mixture of a herbicide, a horsetail, a scabbard, a scabbard, and a ginseng root as an active ingredient.

Since the food composition of the present invention has an effect of growing bone length, it can be used for prevention or improvement of growth disorders.

The growth disorder may be short stature, short stature, or short stature secondary to disease. The normal mutated short stature may be familial short stature, constitutional growth retardation, and idiopathic short stature in agreement. The primary growth disorder may be osteochondral dysplasia, chromosomal aberration (Down syndrome or &lt; RTI ID = 0.0 &gt; Turner syndrome), short stature due to Russell-Silver syndrome, and short stature due to Noonan syndrome. The secondary growth disorders include chronic (chronic) Short stature due to systemic disease, short stature due to growth hormone deficiency, short stature due to hypothyroidism, short stature due to Cushing's syndrome, and psychosocial dwarfism.

The complex extract may be prepared in the same manner as the pharmaceutical composition of the present invention.

The food composition according to the present invention may contain the complex extract of the present invention as it is, or may further contain additives, for example, in other food compositions, health functional foods or beverages.

For example, the food composition of the present invention may contain sweetening agents such as sucrose, fructose, glucose, D-sorbitol, mannitol, isomaltooligosaccharide, stevioside, aspartame, acesulfame potassium, sucralose, Preservatives such as malic acid, benzoic acid and derivatives thereof, various nutrients, vitamins, minerals (electrolytes), flavorings such as synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate Etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks and the like. In addition, the food compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable drinks. These additives may be used in a range of about 20 parts by weight or less per 100 parts by weight of the food composition of the present invention.

When the food composition of the present invention is a beverage, it may further include a flavoring agent or a natural carbohydrate usually contained in beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, polysaccharides such as disaccharides such as maltose and sucrose, dextrin, cyclodextrin or sugar alcohols such as xylitol, sorbitol and erythritol. The flavoring agent may be a natural flavoring agent such as tautatin, stevia extract (rebaudioside A, glycyrrhizin, etc.), or a synthetic flavor such as saccharin and aspartame. If the food composition is a beverage, the natural carbohydrate may generally comprise about 1 to 20 g, preferably about 5 to 12 g per 100 mL of the composition.

The food composition of the present invention may be prepared in the form of powder, granule, tablet, capsule or beverage, and may be used as food, beverage, gum, tea, vitamin complex, and health supplement food.

In addition, the food composition of the present invention may be added to medicines, foods, beverages and the like for promoting bone length growth. For example, the food composition of the present invention may be added to foods, beverages, gums, tea, vitamin complexes, health supplements and the like.

The food composition of the present invention may be added to foods or beverages to promote bone length growth. The composition of the present invention may be added at 1 to 5% by weight of the total weight of the food, and may be added at a ratio of 0.02 g to 10 g, preferably 0.3 g to 1 g, to 100 mL of the beverage.

The pharmaceutical composition or the food composition containing the herbal medicine complex extract according to the present invention as an active ingredient exhibits an effect of promoting bone length growth better than growth hormone.

Fig. 1 is a photograph of a fluorescence microscope photograph of luminescence generated after deposition of a tetracycline in a rat and deposited on a growth plate of a deposited tibia tibia.
2 is a graph showing the degree of bone length growth in a rat.

Hereinafter, preferred examples and examples of the present invention are presented to facilitate understanding of the present invention. However, these preparation examples and examples are provided only for the purpose of easier understanding of the present invention, and the scope of the present invention is not limited by the following production examples and examples.

< Manufacturing example  1> Preparation of complex extract

Dried roots, roots of Acanthopanax senticosus, roots of Acanthopanax senticosus, roots of Acanthopanax senticosus, and roots of Angelica gigas purchased from Kyungdong Market (Seoul) were weighed and weighed so as to have the composition and weight ratio as shown in Table 1, respectively. 70% ethanol corresponding to 10 times the weight of the sample was added, heated for 6 hours under reflux, and filtered under reduced pressure to separate the extract and the residue. 70% ethanol corresponding to 10 times the weight of the sample was added to the residue, and the mixture was extracted with a reflux condenser for 6 hours. Thereafter, each concentrate was obtained by concentrating under reduced pressure using a rotary evaporator under reduced pressure. The concentrate was frozen at -70 ° C. and powder was obtained by using a freeze dryer. The yield of the obtained powder was 19.17% at the speed ratio, 10.55% in the acid ratio, 24.63% in the hwanggi, 10.95% in the sea tangle, and 45.4% in the Chinese ginseng, and the lyophilized powder obtained according to the mixing ratio of the medicinal materials was mixed to obtain the final extract And used as a test sample.

[Table 1]

< Manufacturing example  2 to 6> Preparation of single extract

A single-component composition having the same contents as in Table 2 was prepared by extracting in the same manner as in Preparation Example 1.

[Table 2]

< Example > Of complex extract Bone length  Growth Promotion Effect - Tetracycline dyeing method

1. Outline of experiment

The experimental rats were divided into 9 groups of 7 to 8 animals, saline was administered to the negative control group, the combined extract prepared in Preparation Example 1 was administered to the experimental group at a concentration of 30 and 100 mg / kg (Examples 1 and 2) The single extracts prepared from 2 to 6 were orally administered at a concentration of 100 mg / kg (Comparative Examples 1 to 5) twice daily for 4 days. In the positive control group, growth hormone was injected subcutaneously at a concentration of 20 占 퐂 / Were injected intraperitoneally with tetracycline (10 mg / kg) to allow them to settle on the growth plate. On the 5th day after 48 hours from tetracycline injection, rats were anesthetized with ether and sacrificed.

On the 5th day after the experiment, the tibia isolated from the sacrificed rats was immobilized in 4% phosphate-buffered paraformaldehyde for 48 hours and then dehydrated in 30% sucrose solution. After fixation, the frozen bone was frozen and cryocut was used to cut the proximal part of the proximal tibia (sagittal section) every 40 ㎛ and then used as a tissue specimen. The sections were then used for length growth analysis.

For the measurement of bone length growth, the distance between the growth plate and the colored luminescent line deposited with tetracycline was measured with a fluorescence microscope (see Fig. 1), and the average value for each section was calculated. All procedures were measured by blinded methods by two observers. Results were expressed as means ± SD. Differences between all groups were determined using the Student-T test.

2. Experimental animals

Experimental animals were anesthetized with 3 - week - old SD rats (BIO Korea).

3. Experimental group  Set

Negative Control: Saline

Positive control: Growth hormone 20 ㎍ / kg

Complex extract administration group

Example 1: 30 mg / kg

Example 2: 100 mg / kg

Single extract administration group

- Comparative Example 1: At a constant rate of 100 mg / kg

- Comparative Example 2: Emperor 100 mg / kg

- Comparative Example 3: Acid 100 mg / kg

- Comparative Example 4: 100 mg / kg dry matter

- Comparative Example 5: Angelica gigas 100 mg / kg

4. Experimental conditions

The temperature was 22 ± 2 ℃ and the relative humidity was 50 ± 10%. The light cycle (07:00 lit - 19:00 off) was controlled by fluorescent lighting.

5. Experimental results

As a result, the bone lengths of the negative control group and the positive control group were 327.0 ± 12.9 and 361.0 ± 17.2 μm / day, respectively, and the single extract (Comparative Example 1 to Comparative Example 5) 100 mg / kg group And the bone lengths of the combined extracts 30 and 100 mg / kg (Examples 1 and 2) were 327.1 ± 6.1, 344.5 ± 6.8, 344.9 ± 6.0, 337.9 ± 3.8 and 333.2 ± 6.2 μm / The bone lengths were 379.9 ± 20.8 and 387.5 ± 8.6 μm / day, respectively.

When the growth of the negative control group was taken as 100%, the 100 mg / kg administration group of the single extract (Comparative Example 1 to Comparative Example 5) did not show significant effect, but the positive control group and the combined extract group of 30 and 100 mg / kg administration group 1 and 2) were significantly increased by 10.4% (p <0.01), 16.2% (p <0.001) and 18.5% (p <0.001), respectively, and the growth rate was higher than that of the positive control group ).

The experimental results are summarized in Table 3 below.

[Table 3]

As shown in Table 3, the single extracts of Comparative Examples 1 to 5 showed no significant bone length growth effect, but the combined extracts of Examples 1 and 2 showed positive control (10.4% (16.2% and 18.5%), respectively.

Claims (7)

A pharmaceutical composition for promoting growth of bone length, which comprises as an active ingredient, a complex extract comprising a herbaceous phase, a horsetail, a scabbard, a gooseberry, and Angelica gigantosa. The pharmaceutical composition according to any one of claims 1 to 5, wherein the weight ratio of the above-mentioned starch, acanthol, acacia, acacia, and angelica is 1: 5: 5 to 15:10 to 100: 5 to 15:10 to 50. The pharmaceutical composition according to claim 1, wherein the weight ratio of the above-mentioned starch, hwanggi, mackerel, acanthopanax senticosus and Angelica gigas is 2: 4: 8-12: 40-60: 8-12: 20-30. The pharmaceutical composition according to claim 1, wherein the extract is extracted with water, a C1-C4 alcohol, or a mixed solvent thereof. The method according to claim 1, wherein the promoting of the bone length growth is selected from the group consisting of familial short stature, somatic growth retardation, idiopathic short stature, osteochondral dysplasia, short stature due to chromosomal abnormality (Down syndrome or Turner syndrome) ), Short stature due to Frederick-Willi Syndrome, short stature due to Russell-Silver syndrome, short stature due to Noonan syndrome, short stature due to chronic system disease, short stature due to growth hormone deficiency, short stature due to hypothyroidism, short stature due to Cushing's syndrome And psychosocial dwarfism. &Lt; RTI ID = 0.0 &gt; &lt; / RTI &gt; A composition for accelerating growth of bone length, which comprises as an active ingredient, a complex extract comprising a herbaceous plant, a herbaceous plant, a herbal medicine, acanthopanax senticosus, and Angelica gigantosum. The food composition according to claim 6, which is a health functional food.

Images