The present invention relates to a pharmaceutical or a food composition for inducing or stimulating secretion of insulin-like growth factor-1. More particularly, the present invention relates to compositions for inducing or stimulating secretion of insulin-like growth factor-1, which comprises (a) a pharmaceutically effective amount of an extract obtained from oriental pharmaceutical selected from the group consisting of Phlomis umbrosa Turez, Cynanchum wilfordii(Max) Hem≦, Zingiber officinale Rosc., Platycodi Radix and combination thereof; and (b) a pharmaceutical acceptable carrier.

SUMMARY OF THE INVENTION

Under such circumstances, the inventor has made intensive study to develop effective substances or compositions capable of increasing IGF-1 level in body. As a result, the inventor has found that extracts from several oriental pharmaceuticals is very effective in inducing or stimulating secretion of IGF-1.

Accordingly, it is an object of this invention to provide a pharmaceutical composition for treating or preventing a disorder associated with reduced serum insulin-like growth factor-1 level.

It is another object of this invention to provide a food composition for inducing secretion of insulin-like growth factor-1.

Other objects and advantages of the present invention will become apparent from the detailed description to follow taken in conjugation with the appended claims and drawings.

DETAILED DESCRIPTION OF THIS INVENTION

In one aspect of this invention, there is provided a pharmaceutical composition for treating or preventing a disorder associated with reduced serum insulin-like growth factor-1 level, which comprises (a) a pharmaceutically effective amount of an extract obtained from oriental pharmaceutical selected from the group consisting of Phlomris umbrosa Turez, Cynanchum wilfordii(Max) Hem&ley, Zingiber officinale Rosc., Platycodi Radix and combination thereof; and (b) a pharmaceutical acceptable carrier, wherein the extract as active ingredient induces secretion of insulin-like growth factor-1.

In another aspect of this invention, there is provided a food composition for inducing secretion of insulin-like growth factor-1, which comprises, as active ingredient, an extract obtained from oriental pharmaceutical selected from the group consisting of Phlomis umbrosa Turez, Cynanchum wilfordii(Max) Hem&ley, Zingiber officinale Rosc., Platycodi Radix and combination thereof.

The present compositions capable of inducing secretion of IGF-1 can ameliorate various disorders or diseases associated with reduced serum IGF-1 level. For example, the compositions are found to improve body composition, insulin sensitivity, bone mineral density and linear growth; to inhibit mental retardation, microcephaly, sensorineural deafness and femoral bone loss in postmenopausal women; to stimulate neural stem cell proliferation; and to prevent poor muscle strength and mobility in older women. Furthermore, the present compositions can facilitate linear growth in young men who are poor in growth.

The present inventor has focused on oriental pharmaceuticals to screen candidates for inducing IGF-1, since oriental pharmaceuticals have been already proved to exhibit safety to human, which is confirmed through several facts: (a) oriental pharmaceuticals are derived from natural source, generally, plants, and (b) have been conventionally employed as pharmaceuticals. Through screening a wide variety of oriental pharmaceuticals for inducing IGF-1, Phlomis umbrosa Turez, Cynanchum wilfordii(Max) Hem&ley, Zingiber officinale Rosc. and Platycodi Radix have been proved to exhibit considerable ability to induce IGF-1.

Among the raw materials, Phlomis umbrosa Turez is a perennial plant with typical height of 1 m and has been known to have pharmacological efficacy in protection of liver and kidney. Cynanchum wilfordii(Max) Hem&ley is a perennial plant and has been employed to treat or prevent anemia, astriction, ulcer and the like in the Oriental countries such as Korea and China. Zingiber officinale Rosc. is a kind of plant belonged to Zingiberaceae and has been reported in the Oriental countries to have pharmacological efficacy including prevention of vomiting, relief of pains and prevention of aggregation of platelet.

Platycodi Radix is generally meant to a root of Platycodon grandiflorum (Jacq.)A,. DC. belonged to Campanulaceae and has been known in the Oriental countries to exhibit antitussive and pectoral efficacy.

The present inventor has found novel use of the above-described oriental pharmaceuticals to induce or stimulate secretion of IGF-1 in vivo.

Meanwhile, the process for preparing extracts from the oriental pharmaceuticals incorporated into compositions of this invention must be provided in consideration of isolation of active ingredients with significant purity. In particular, the process of this invention must be designed to allow cost-effectiveness, and maintenance and evaluation of physiological activity of the resulting extract. Since the oriental pharmaceuticals used in this invention are highly expensive, the cost-effectiveness of the process appears to be very important factor to be considered.

In this regard, the present inventor has developed a novel process for preparing extracts from the oriental pharmaceuticals, which permits the extracts to be prepared in a cost-effective and massive manner while loss of active ingredients in the oriental pharmaceuticals may be negligible. Furthermore, although the process is very simple, it is significantly effective in preparing extracts.

According to preferred embodiment of this invention, the extract to be incorporated into the present compositions is prepared in accordance with the process comprising the steps of (a) extracting oriental pharmaceutical selected from the group consisting of Phlomis umbrosa Turez, Cynanchum wilfordii(Max) Hem&ley, Zingiber officinale Rosc., Platycodi Radix and combination thereof with hot water, whereby a crude extract is obtained; and (b) filtering the crude extract by means of ultrafiltration membrane with molecular weight cut off of 30,000-100,000.

The first extraction employs water as extraction solvent in order to avoid the contamination of the final product by harmful substances to human. Therefore, according to preferred embodiment of this invention, organic solvents such as methanol are not employed.

It is preferable that the hot water employed in first extraction has a temperature ranging from 60° C. to 95° C. If the temperature is lower than 60° C., the extraction of active ingredients for inducing secretion of IGF-1 may be far poor; while if the temperature is higher than 95° C., active ingredients may be destroyed or disrupted in accelerated manner. More preferably, the hot water has a temperature ranging from 80° C. to 90° C. According to preferred embodiment of this invention, the crude extract thus yielded is then cooled, and is subject to centrifugation or paper filtration to remove precipitate.

Thereafter, the resulting crude extract is separated on the basis of molecular weight, finally obtaining desired extract containing active ingredients with relatively low molecular weight. According to this invention, the separation according to molecular weight is carried out by filtration using ultrafiltration membrane with certain molecular weight cut off range. Among various methods, the present inventor has proved that the filtration using ultrafiltration membrane is the most preferable in view of various considerable factors including yield, convenience and cost-effectiveness.

The ultrafiltration membrane used in this invention has typically molecular weight cut off ranging from 30,000 to 100,000. If molecular weight cut off is lower than 30,000, the separation may require much longer time so that cost-effectiveness of the process may be far poor. If molecular weight cut off is more than 100,000, the separation of active ingredients with low molecular weight from molecules with high molecular weight may be negligible so that the relative purity of the final extract may be too low. According to preferred embodiment of this invention, the ultrafiltration membrane has a molecular weight cut off ranging from 50,000 to 100,000.

In preferred embodiment of this invention, the extract thus obtained is concentrated to prepare high concentrated extract. The concentration is performed according to various methods known to one skilled in the art, for example, heating in reduced pressure. If necessary, the concentrated extract is processed to give powder by means of various methods known to one skilled in the art, for example, drying in reduced pressure.

As described above, the process for preparing desired extract can be carried out with feasibility and cost-effectiveness and allow to obtain active ingredients for inducing secretion of IGF-1 with high purity and yield.

According to preferred embodiment of this invention, if necessary, the present composition further comprises calcium, arginine, lysine and/or carboxymethyl cellulose. Calcium is main mineral component of bone, arginine may allow to enhance secretion of growth hormone in body, lysine may promote the action of arginine and carboxymethyl cellulose may prevent wetting to inhibit growth of microorganisms and may facilitate homogeneous mixing of several ingredients in a composition. More preferably, the amount of calcium is 65-80 parts by weight, the amount of arginine is 25-40 parts by weight, the amount of lysine is 5-20 parts by weight and the amount of carboxymethyl cellulose is 2-8 parts by weight based on 100 parts of extract from oriental pharmaceuticals.

In the pharmaceutical compositions of this invention, the pharmaceutically acceptable carrier may be conventional one for formulation, including carbohydrates (e.g., lactose, amylose, dextrose, sucrose, sorbitol, mannitol, starch), gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, salt solutions, alcohols, gum arabic, syrup, vegetable oils (e.g., corn oil, cotton-seed oil, peanut oil, olive oil, coconut oil), polyethylene glycols, methyl cellulose, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate and mineral oil, but not limited to. The pharmaceutical compositions of this invention, further may contain wetting agent, sweetening agent, emulsifier, buffer, suspending agent, preservatives, flavors, perfumes, lubricant, stabilizer, or mixtures of these substances.

It is especially preferred that the pharmaceutical compositions of this invention are orally administered. The compositions of this invention are very effective in treating or prevention various disorders and diseases associated with reduced serum IGF-1 level, especially, improving body composition and week constitution, and preventing osteoporosis and aging.

The pharmaceutical composition of this invention can stimulate or induce secretion of IGF-1 so that it permits treatment of growth failure, facilitation of linear growth in young men, improvement of bone mineral density (prevention and treatment of osteoporosis), prevention of aging, improvement of body composition, treatment of femoral bone loss in postmenopausal women and protection of neural cells.

The correct dosage of the pharmaceutical compositions of this invention will be varied according to the particular formulation, the mode of application, age, body weight and sex of the patient, diet, time of administration, condition of the patient, drug combinations, reaction sensitivities and severity of the disease. It is understood that the ordinary skilled physician will readily be able to determine and prescribe a correct dosage of this pharmaceutical compositions. An exemplary daily dosage unit for human host comprises an amount of from about 5 mg/kg to about 100 mg/kg.

According to the conventional techniques known to those skilled in the art, the pharmaceutical compositions of this invention can be formulated with pharmaceutical acceptable carrier and/or vehicle as described above, finally providing several forms including a unit dosage form. Non-limiting examples of the formulations include, but not limited to, a solution, a suspension or an emulsion, an extract, an elixir, a powder, a granule, a tablet, a capsule, emplastra, a liniment, a lotion and an ointment.

In a food composition of this invention, it can comprise typical ingredients incorporated in food products known to one skilled in the art. Typical food ingredients will include protein, carbohydrates, fats, nutrients and flavors. Preferred food products are drinks, concentrated drinks and instant drinks comprising e.g. citric acid, aqueous fructose, sucrose, glucose, acetic acid and/or fruit juice. Another preferred food products are in the form of powder comprising e.g. essential amino acids such as lysine, arginine, ornithine, glycine and tryptophan, niacin or gamma-hydroxy butyrate.
 

Claim 1 of 7 Claims

1. A food composition for inducing secretion of insulin-like growth factor-1, which comprises, as active ingredient, an extract obtained from Phlomis umbrosa Turcz; in which the extract is prepared by a process comprising the steps of (i) extracting Phlomis umbrosa Turcz with hot water, whereby a crude extract is obtained; and (ii) filtering the crude extract by means of an ultrafiltration membrane with molecular weight cut off of 30,000-100,000.

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