KR101138994B1 - Compositions for promoting growth - Google Patents

Abstract

PURPOSE: A composition containing extract of Phlomis umbrosa Turez and Commelina communis is provided to stimulate or induce secretion of IGF-1(insulin-like growth factor-1). CONSTITUTION: A food composition for improving growth contains extract of Phlomis umbrosa Turez and Commelina communis as an active ingredient. A functional food composition for improving growth contains the extract as an active ingredient. A pharmaceutical composition for promoting growth contains the extract as an active ingredient. The dose of the pharmaceutical composition is 0.001-1000 mg/kg. The composition is manufactured in the form of a solution in oil or aqueous medium, suspension, syrup, emulsion, powder, granules, tablet, or capsule.

Description

Composition for Promoting Growth

The present invention relates to a growth promoting composition.

Insulin-like growth factor-1 (hereinafter referred to as “IGF-1”) is a single-chain polypeptide consisting of 70 amino acids and is primarily secreted by the liver. IGF-1 exerts its function through the IGF-1 receptor. Many studies have been conducted on the in vivo functions of IGF-1, and such studies have identified various functions other than promoting IGF-1 growth, such as promoting protein synthesis, reducing blood glucose levels, and promoting cell differentiation.

For example, it has been reported that IGF-1 is essential for the proliferation of neuronal stem cells, and is directly linked to a decrease in muscle strength and exercise capacity and a decrease in the in vivo concentration of IGF-1 in older women. Is reported. In addition, it has been reported that regeneration of skeletal muscle can be performed through IGF-1, and bioavailability of IGF-1 is greatly reduced after ethanol overdose. On the other hand, it has been reported that IGF-1 plays an important role in cell proliferation, and it has been reported that IGF-1 has a therapeutic effect in diabetic patients (types 1 and 2) (Thraikill KM, Diabetes). Technol Ther., 2 (1): 69-80 (2000).

Low blood levels of IGF-1 were directly associated with femoral decline in postmenopausal women, and a rapid decrease in IGF-1 was reported in the acute stage of myocardial infarction. Various reports have shown that IGF-1 has cellular protection against ischemia-reperfusion injury in various organs, and has been demonstrated to be capable of inhibiting neuronal cell death.

Woods KA. et al., N. Engl . J. Med . 335: 1363 (1996), in patients with IGF-1 deficiency suffer from lack of postnatal growth, delayed mental development, microcephaly and numbness of the sensory nerves. Normal secretion is achieved and signaling by growth hormone is normal, but IGF-1 is not produced locally or systemically. Administration of IGF-1 to patients deficient in IGF-1 has also been shown to improve gymnastics, insulin sensitivity, bone mineral density and length growth (KA Woods. Et al., J. Clin. Endocri. & Met. 85: 1407 (2000).

Blum et al . ( J. Clin . Endocrinol . Metab . 76: 1610-1616 (1993)) show that young men who exhibit low concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3) are generally short. And Ranke et al . , Horm . Res . 44: 253-264 (1995) reported that long-term treatment with IGF-1 is very effective in increasing the length growth rate. In other words, IGF-1 is very useful for the treatment of patients suffering from growth hormone deficiency.

As mentioned above, IGF-1 exhibits various physiological functions in conjunction with growth hormone or in an independent manner.

US Pat. No. 5,240,961 discloses a method for treating bone loss and reduction of aging-related insulin-like growth factors comprising administering L-carnitine and / or its precursors. US Pat. No. 5,466,670 discloses a method for treating Type 1 diabetes by subcutaneously administering IGF-1 to 400 ng / ml or less, which is a characteristic serum concentration in healthy individuals.

In addition, US Pat. No. 5,861,373 discloses a method of treating neuronal damage following CNS insults that affect glial or other noncholinergic cells in a mammal, which method provides for the biological treatment of IGF-1 and / or IGF-1. Administering a medicament comprising an effective amount of the active analog to the mammal's central nervous system.

To date, no active substances and compositions that increase the concentration of IGF-1 in vivo have been developed. Therefore, there is a long demand for the development of materials and compositions for treating patients suffering from IGF-1 deficiency.

Throughout this specification, numerous papers and patent documents are referenced and their citations are indicated in parentheses. The disclosures of cited papers and patent documents are incorporated herein by reference in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly described.

Under the circumstances of the prior art described above, the present inventors have tried to develop effective substances and compositions that increase the concentration of IGF-1 in vivo. As a result, the present inventors found that the Sokdan and Dolby extracts have excellent IGF-1 inducing activity among various herbal medicines, and in particular, the mixture of Sokdan and Dalsy extract has very good IGF-1 inducing activity, thereby promoting growth. By clarifying, this invention was completed.

Accordingly, it is an object of the present invention to provide a composition for promoting growth through IGF-1 inducing activity.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to an aspect of the present invention, the present invention provides a composition for promoting growth comprising a fast extract and colic extract as an active ingredient.

According to another aspect of the present invention, the present invention provides a composition for promoting growth comprising the extract of the algae as an active ingredient.

The present inventors have tried to develop effective substances and compositions that increase the concentration of IGF-1 in vivo. As a result, the present inventors found that the Sokdan and Dolby extracts have excellent IGF-1 inducing activity among various herbal medicines, and in particular, the mixture of Sokdan and Dalsy extract has very good IGF-1 inducing activity, thereby promoting growth. It was clarified.

Compositions of the invention capable of inducing secretion of IGF-1 (insulin-like growth factor-1) can improve gymnasticity, bone mineral density and length growth. Moreover, the composition of the present invention can promote the growth of the length of young people with poor growth.

The present inventors focused on herbal medicines in screening candidates capable of inducing IGF-1, since herbal medicines have conventionally been proven to be safe for humans: (a) Herbal medicines are natural sources, Generally derived from plants, (b) herbal medicines are commonly used as medicines.

Through this screening, it was found that the Sokdan and Dalby extracts have excellent IGF-1 inducing activity among various herbal medicines, and that the mixture of Sokdan and Dalsy extract is particularly excellent in IGF-1 inducing activity, thereby promoting growth. It was.

Phlomis umbrosa Turez ) is a perennial herb that is 1 m high and is known to have pharmacological effects on protecting the liver and kidneys.

Moonfish ( Commelina communis ) is an annual herb with chickweed. In oriental medicine, clear heat detoxification, wind fever, wind fever, fever, sore throat, water swelling, urinary tract pain, and It is known to treat Ongjong Jungpok.

The composition of the present invention includes a fast extract and a dalpa extract as an active ingredient. As used herein, the term 'extract' used while referring to fasting and decoction is formulated (eg, powdered) so that the fasting and decoction itself can be administered to the animal as well as the extraction result obtained by treating the extracting solvent in the fasting and decoction. It also has the meaning of including the fast and cockerel workpieces.

Sokkwan and cogwheel extract of the present invention means that it is obtained by extracting from various organs, such as leaves, flowers, roots, stems, buds, branches, bark and fruit of the sokdan and cogwheel.

In the case of fasting and deciduous extract used in the composition of the present invention obtained by treating the extracting solvent to the fast and deciduous ratio, a variety of extracting solvent may be used. Preferably, a polar solvent or a nonpolar solvent can be used. Suitable polar solvents include (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, normal-butanol, 1-pentanol, 2-butoxyethanol Or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO) and (v) dimethyl sulfoxide (DMSO). Suitable as nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- Pentene, 1-chlorobutane, 1-chloropentane, o -xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloro Methane, 1,2-dichloroethane, anneal, diethylamine, ether, carbon tetrachloride and THF.

As used herein, the term "extract" has the meaning commonly used as a crude extract in the art as described above, but also broadly includes a fraction additionally fractionating the extract. That is, the fast and dalgan extract is not only obtained by using the above-mentioned extraction solvent, but also includes those obtained by additionally applying a purification process. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. Fractions obtained through the purification method are also included in the fast and calf extract of the present invention.

Fast-acting and coriander extract used in the present invention may be prepared in a powder state by an additional process such as vacuum distillation and freeze drying or spray drying.

In the composition of the present invention, the content of the fast extract and calendula extract is not limited. For example, 10-99% by weight fast extract and 1-90% by weight extract, fast extract 10-90% by weight extract and 10-90% by weight extract extract, 20-90% by weight fast extract and 10-80% by weight extract May contain%.

The composition of the present invention may be prepared as a pharmaceutical composition.

According to a preferred embodiment of the present invention, the composition of the present invention comprises (a) a pharmaceutically effective amount of the above-described moonshine extract; And (b) a pharmaceutically acceptable carrier. As used herein, the term “pharmaceutically effective amount” means an amount sufficient to achieve the efficacy or activity of the above-mentioned moonshine extract.

When the composition of the present invention is made into a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention may be administered orally or parenterally, and preferably applied by oral administration.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . Typical dosages of the pharmaceutical compositions of the invention are in the range of 0.001-1000 mg / kg on an adult basis.

The pharmaceutical compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. The formulation may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of extracts, powders, powders, granules, tablets or capsules, and may further comprise dispersants or stabilizers.

The composition of the present invention may be provided as a food or functional food composition.

According to a preferred embodiment of the present invention, the composition of the present invention comprises (a) a food-effective amount of the above-described moonshine extract of the present invention; And (b) a food acceptable carrier.

When the composition of the present invention is made of a food or functional food composition, as an active ingredient, as well as extracts of fasteners and coriander, as well as components commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, Seasonings and flavoring agents. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared with a drink, it may further include citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract, etc. have.

Since the composition of the present invention can stimulate or induce the secretion of IGF-1, it can act as a treatment for growth sluggishness and promote the growth of length.

The features and advantages of the present invention are summarized as follows:

(Iii) The present invention provides a composition for promoting growth using fast-acting and decoction.

(Ii) Since the composition of the present invention can stimulate or induce the secretion of IGF-1, it can act as a treatment for growth inferiority and promote growth in length.

(Iii) Sokdan and Dalby extract as an active ingredient in the composition of the present invention has been used conventionally as a herbal medicine, it is also excellent in safety.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it is to those of ordinary skill in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. Will be self-evident.

Example

Example I Preparation of Extracts Containing Low Molecular Weight Active Ingredients from Rapid and Wolverine

I-1. Speed (Phlomis umbrosa Turez ) Extract

Sokdan was purchased from Gyeongdong Market (Seoul, Korea) and used as a raw material. 1.5 L of distilled water was added to 50 g of the dried fastener, and heated at 80-90 ° C. for 2 hours to obtain 0.7 L of an aqueous extract. Distilled water corresponding to half of the amount added at the time of the first extraction was added to the remaining fast, and heated at 80-90 ° C. for 2 hours for extraction. One liter of the extract obtained in the first and second extraction was collected and heated at 90 ° C. to concentrate the volume of the extract to the final 500 ml.

500 ml of the obtained extract was centrifuged at 3000 xg for 10 minutes, and then the supernatant was passed through a filtration membrane of molecular weight cutoff (MWCO) 50,000 or 100,000 using a stirred cell apparatus (Amicon, USA). . At this time, the pressure of nitrogen added was fixed at 3 atmospheres. On the other hand, if the ultrafiltration membrane was blocked, work was continued by replacing with a new ultrafiltration membrane. Clogged membranes were washed and reused with 0.1N NaOH and 20% ethanol.

In order to calculate the extraction efficiency, the extract obtained in each step was dried under reduced pressure (Freeze dryer, Edwards, United States of America), and the extraction efficiency was calculated based on the weight of the powder (see Table 1).

step Weight (g) Extraction efficiency (%) Early herbs 50 100 Heating and extraction stage 19.5 39 MWCO 50,000 Filtration 16.7 33.54 MWCO 100,000 filtration 18.5 37

The extraction efficiencies of the heating and extraction steps were slightly varied with each run and generally showed extraction efficiencies of 38% -45%. From the standpoints of extraction efficiency and purity of the active ingredient having IGF-1 secretion inducing ability, it can be seen that a molecular weight cutoff of 100,000 or less is preferable.

I-2. Moonfish ( Commelina communis ) extract

It was purchased at Gyeongdong Market (Seoul, Korea) and used as a raw material. To prepare a wolveseun extract in the same manner as in Example I-1, 50 grams were used instead of fast 50g. The extraction efficiency was calculated based on the weight of the powder (see Table 2).

step Weight (g) Extraction efficiency (%) Early herbs 50 100 Heating and extraction stage 18.2 36.4 MWCO 50,000 Filtration 15.3 30.6 MWCO 100,000 filtration 16.8 33.6

The extraction efficiencies of the heating and extraction stages were slightly varied with each run and generally showed extraction efficiencies of 30% -37%. From the standpoints of extraction efficiency and purity of the active ingredient having IGF-1 secretion inducing ability, it can be seen that a molecular weight cutoff of 100,000 or less is preferable.

In conclusion, the extract of the active ingredient having the ability to induce IGF-1 secretion is efficiently and conveniently prepared from fasting and cochlea, and this process includes (a) hydrothermal extraction, and (b) molecular weight cutoff of 30,000- Filtration step using an ultrafiltration membrane of 100,000. In addition, the temperature of the hot water in the extraction process is preferably 80 ℃ to 90 ℃, MWCO of the ultrafiltration membrane used for filtration is preferably 50,000 to 10,000.

Example II : By the extract of the present invention IGF -1 secretion induction

In Example I, 252 mg of the powder obtained by using an ultrafiltration membrane of MWCO 50,000 was dissolved in 1 ml of distilled water, and used as a dose. The animals used in this example are 9-week-old Sprague Dawley male rats with an average weight of about 300 g. The experimental animals were fasted for one day prior to administration of the extract of the present invention for the purpose of enhancing the responsiveness to the secretory stimulation of IGF-1. The number of animals was 6 in the control group and 20 in the experimental group. On the other hand, in the complex extracts, coriander and Sokcheol administration solution was prepared by mixing 500 μl of the administration solution for each extract prepared as described above to prepare a 1000 μl of the dosage of the complex extract.

The rat was orally administered with 1000 μl of the dose using an oral syringe. Blood was collected directly from the heart before and at 2, 4, 6, 8 and 10 hours after administration. In addition, anesthetics that may affect the secretion pattern of IGF-1 were not used during the experiment.

Then, the quantification of IGF-1 in the collected samples was carried out according to the manufacturer's protocol using the enzyme immunoassay kit (Diagnostic System Laboratory, United States of America), the results are shown in Table 3 below.

Item Blood IGF-1 Concentration (ng / ml) 0 2 hours 4 hours 6 hours 8 hours 10 hours Fast 1200 1140 1135 1131 1115 1023 Moon 1200 1138 1131 1050 1043 930 Moon + Fast 1200 1160 1159 1158 1152 1143 Control group 1200 1130 1050 980 950 900

As can be seen in Table 3, the experimental group to which the composition of the present invention comprising the fast extract and colic extract shows a significantly higher concentration of blood IGF-1 compared to the control group after 4 hours after administration. Therefore, it can be seen that the extract of the present invention is effective in raising the concentration of blood IGF-1 in animals. In addition, serum IGF-1 concentration reached its highest point 8 hours after administration. The composition of the present invention comprising a fast extract and a fern extract exhibited a synergistic IGF-1 synergistic effect compared with the case of administering a fast extract or a fern extract individually.

Example  III: Evaluation of Bone Formation by Extracts of the Present Invention

In Example I was prepared a feed containing a powder obtained using an ultrafiltration membrane of MWCO 50,000. The composition of the feed is shown in Table 4 below.

ingredient Content (mg) Fast extract 30 Moonshine effluent 20 Seaweed calcium 37.5 Arginine 16.8 Lysine 5.6 Carboxy Methyl Cellulose 2.25

The total weight of the feed was 15 g and other ingredients commonly used in animal feed were also added to the feed.

The animal used in this example is a 3 week old Sprague Dawley male rat. Long-term (8 weeks) long-term administration of the feed to the experimental animals, rats were sacrificed, and the femoral and shin bones were removed to determine the change in length growth. The number of control and experimental groups was 4, respectively. The control group is a group of animals that are allowed to take the feed except the extract of the present invention.

As a result, the control group showed little change in the length of the thigh and shin bones after 8 weeks of long-term administration. However, rats treated with fast and calf extract-containing feeds in Table 4 increased femoral and shin bones by 5 mm and 3 mm, respectively, after 8 weeks of long-term administration.

Thus, it can be reconfirmed that fasting and cogwheel extracts can stimulate bone formation, which promotes length growth.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Claims (5)

Growth improvement food composition comprising a Sokpan extract and a wolverine extract as an active ingredient.
The composition of claim 1, wherein the composition induces secretion of insulin-like growth factor-1 (IGF-1).
delete Functional food composition for growth improvement, including Sokdan extract and coriander extract as an active ingredient.
Growth promoting pharmaceutical composition comprising a Sokpan extract and a wolverine extract as an active ingredient.