KR20020052034A - Phamaceutical composition comprising SEPIAE OS, EUCOMMIAE CORTEX, ACANTHOPANACIS CORTEX, TESTUDINS PLASTRUM, ACHYRANTHIS BIDENTATAE RADIX AND CIBOTIUM BAROMEZ L as main ingredients and pharmaceutical preparations containing them - Google Patents

Abstract

PURPOSE: A pharmaceutical composition obtained by powdering natural drugs, extracting, mixing thus obtained extract, or extracting with a necessary natural drug component is provided. Therefore, the composition is excellent in prevention and treatment of osteoporosis, rheumatoid arthritis, hernia of intervertebral discs or the like. CONSTITUTION: The composition contains an extract of Sepiae Os, Eucommiae cortex, Acanthopanacis cortex, Testudinis plastrum or Trionycis carapax, Achyranthis bidentatae radix and Cibotii Rhizoma or Cibotium baromez(L.) and if necessary, Hordei Fructus Germinatus, Rehmanniae Radix Preparat, Cinnamomi Cortex, Carthami Fructus, Glycyrrhizae Radix, Lycii Fructus, Dipsaci Radix, Cervi Cornu, Salviae Miltiorrhizae Radix, fructus Crataegi, Scrophulariae Radix, Leonuri Herba, Massa Medicata Fermentata, Sojae Semen and Phaseoli Semen, wherein the extract is added with an auxiliary agent and then formulated into a capsule, tablet, pill or the like.

Description

Pharmaceutical composition containing main ingredient, Ohjeolgol, hyssop, head chops, scabies, fern and spherical plate, and pharmaceutical preparations containing it as main ingredient L as main ingredients and pharmaceutical preparations containing them}

The present invention is the SEAPIAE OS, EUCOMMIAE CORTEX, ACANTHOPANACIS CORTEX, Gupan (or Grow: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX), Ussel (ACHYRANTHIS BIDENTATAE RADIX) and Gobi (Colgu: CIBOTII RH IZU) The present invention relates to a pharmaceutical composition containing CIBOTIUM BAROMEZ (L.) As a main component and a pharmaceutical formulation thereof.

At present, the cases of complaints with various bone diseases in Korea are known to increase every year. However, chemotherapy and surgery, which are used for the treatment of bone diseases, have not yet achieved perfect results. These bone diseases are progressing from chronic to degenerative due to aging and the medical burdens as well as the pain accompanying them are required to develop new materials that can be utilized in the clinical field as a whole.

Rheumatoid arthritis and degenerative arthritis, known as adult disease and senile disease, are known to be refractory diseases, and these diseases are known to be caused by the activation of synovial cells of the joints and their aging and autoimmune factors. Rheumatoid and degenerative arthritis can be cured by developing drugs that kill or inhibit arthritis cells or inhibit or inhibit the expression of cyclooxygenase II (COX-II), an enzyme produced by these cells.

The present inventors have conducted a long study on herbal medicines that can be used for rheumatoid arthritis, degenerative arthritis, and disc diseases of the waist and neck. The result is SEAPIAE OS, EUCOMMIAE CORTEX, ACANTHOPANACIS CORTEX, Gupan (or Grow: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX), Ussel (ACHYRANTHIS BIDENTATAE RADIX) and Gobi (Biopharmaceuticals; Guzumi CIBOM II Contains as its main ingredient one or more components selected from powders of CIBOTIUM BAROMEZ (L.) Or extracts selected from solvents selected from water, lower alcohols, ethyl acetate, aromatic hydrocarbons, and chlorinated hydrocarbons, including the malt (HORDEI FRUCTUS GERMINIATUS) , ANGELICAE GIGANTIS RADIX, SUKJIANG (REHMANNIAE RADIX PREPARAT), broiler (CINNAMOMI CORTEX), safflower (CARTHAMIFRUCTUS), licorice (GLYCYRRHIZAE RADIX), goji berry (LYCII FRUCTUS), ROCK (CIX) Salvia (SALVIAE MILTIORRHIZAE RADIX), Sansa (CRATAEGII FRUCTUS), Hyunsam (SCROPHU LARIAE RADIX), Motherwort (LEONURI HERBA), New Song (MASSAMEDICATA FERMENTATA), Soybean (SOJAE SEMEN), Red Bean (PHASEOLI SEMEN) Extracted with a solvent selected from the above supplement or a solvent selected from water, lower alcohol, ethyl acetate, aromatic hydrocarbon, or chlorinated hydrocarbon, X has found the surprising fact that inhibits arthritis and inflammation in molecular biological experiments and animal experiments to complete the present invention.

As a result of active research on bone disease worldwide, as a result of the rapid increase in the bone marrow immunity, the pathogenesis of bone disease and the pathogenesis of arthritis have been revealed. Recently, several osteoporosis treatments have been developed and allenradates. , tamoxifen (tamoxifen), vitamin D ₃ (vitamin D _3), PTH (parathyroid hormone: PTH) and of sulfasalazine (sulfasalazine) were successful as the COX-II inhibitors are already commercialized in treating rheumatoid arthritis, wherein the anti-inflammatory agent (Becker K, Gromer S, Schirmer RH, Muller S. Thioredoxin reductase as a pathophysiological factor and drug target.Eur.J. Biochem., 2000 Oct 15; 267 (20): 6118-6125), thioredoxin reductase (a pathophysiological factor and drug target.Eur J. Biochem. 2000 Oct 15; 267 (20): 6118-6125 and the like are known and are in clinical or research and development, and as the treatment for osteoporosis, alendronate and raloxifene ), Calcitonin (Moraghan TJ, Perez EA. Mayo Clin Proc. 2000 Aug; 75 (8): 821-9.), Estradiol (Andersson TL, Stehle B, Davidsson B, Hoglund P. Maturitas) 2000 Jun 30; 35 (3): 245-52), genistein (Mazurek AP. Polkowski K.Acta Pol Pharm. 2000 Mar-Apr; 57 (2): 135-55., 1,25-dihydroxyvitamin D (3) (Am. J. Physiol. Endocrinol. Metab. 2000 Jul; 279 (1): E213-20), parathyroid hormone (Hunziker J, Wronski TJ, Miller SC. J. Dent. Res. 2000 Jun; 79 (6): 1431-8), alendronate (Kashyap AS, Kashyap S. Postgrad Med J. 2000 Jul; 76 (897): 417-8), estrogen receptor modulators, calcitonin, and bisphosphonates (Wimal-awansa SJ. J. Clin. Densitom. 2000 Summer; 3 (2): 187-201).

Accordingly, the present invention is 10 to 200 parts by weight of the seopgolgol (SEPIAE OS), Gobi (crack: CIBOTII RHIZOMA: 50 to 500 parts by weight of CIBOTIUM BAROMEZ (L.), 50 to 500 parts by weight of the dew (ACHYRANTHIS BIDENTATAE RADIX) , 50 to 500 parts by weight of EUCOMMIAE CORTEX, 50 to 500 parts by weight of ACANTHOPANACIS CORTEX, and 50 to 500 parts by weight or sphere (or TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX) or its extract, if necessary Malt (HORDEI FRUCTUS GERMINIATUS) 10-200 parts by weight, 50-500 parts by weight of ANGELICAE GIGANTIS RADIX, 50-500 parts by weight of REHMANNIAE RADIX PREPARAT, wind-proof (LEDEBOURIELLAE RADIX) 50-500 parts by weight, CINNAMOMI CORTEX) 50-500 parts by weight, 50-500 parts by weight of CARTHAMI FRUCTUS, 10-200 parts by weight of SCOLOPENDRA, 10-200 parts by weight of windproof (LEDEBOURIELLAE RADIX), 10-200 parts by weight of licorice (GLYCYRRHIZAE RADIX) , LYCII FRUCTUS 50-5 00 parts by weight, 100 to 500 parts by weight of DIPSACI RADIX, 100 to 500 parts by weight of CERVI CORNU, 20 to 200 parts by weight of SALVIAE MILTIORRHIZAE RADIX, 10 to 200 parts by weight of Sansa (CRATAEGII FRUCTUS) (SCROPHULARIAE RADIX) 10 to 200 parts by weight, 100 to 500 parts by weight of motherwort (LEONURI HERBA), 50 to 500 parts by weight of MASSA MEDICATA FERMENTATA, 50 to 500 parts by weight of SOJAE SEMEN, PHASEOLI SEMEN 10 To extracts containing at least one auxiliary supplement selected from 200 parts by weight or a solvent extracted from water, lower alcohol, ethyl acetate, aromatic hydrocarbons or chlorinated hydrocarbons thereof to inhibit arthritis and inflammation in molecular biological experiments and animal experiments. It gives an amazing effect.

In other words, the object of the present invention, SEAPIAE OS, Stomach (EUCOMMIAE CORTEX), OGAPI (ACANTHOPANACIS CORTEX), Gupan (or Grow: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX), Umbrella (ACHYRANTHIS BIDENTATAE RADIX) and Gobi CIBOTII RHIZOMA: Contains CIBOTIUM BAROMEZ (L.) Powder or extract extracted with water, lower alcohol, ethyl acetate, aromatic hydrocarbons, chlorinated hydrocarbons, as a main ingredient, and if necessary, HORDEI FRUCTUS GERMINIATUS, REHMANNIAE RADIX PREPARAT, Broiler CINNAMOMI CORTEX, CARTHAMI FRUCTUS At least one supplementary herb selected from CRATAEGIIFRUCTUS, SCROPHULARIAE RADIX, motherwort (LEONURI HERBA), new song (MASSA MEDICATA FERMENTATA), soybean (SOJAE SEMEN), red bean (PHASEOLI SEMEN) or its water, low alcohol, acetic acid Ethyl, aromatic Hydrogen, osteoporosis, extracted with a solvent selected from chlorinated hydrocarbons, rheumatoid arthritis, compositions which are highly effective in the prevention and treatment of disc symptoms, and to provide a pharmaceutical preparation containing the same.

Another object of the present invention is 10 to 200 parts by weight Oseogolgol (SEPIAE OS), CIBOTII RHIZOMA: 50 to 500 parts by weight of CIBOTIUM BAROMEZ (L.), 50 to 500 parts by weight of dew (ACHYRANTHIS BIDENTATAE RADIX), 50-500 parts by weight of EUCOMMIAE CORTEX, 50-500 parts by weight of ACANTHOPANACIS CORTEX, 50-500 parts by weight of spherical (or growing) TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX or its extract, if necessary (HORDEI FRUCTUS GERMINIATUS) 10 to 200 parts by weight, 50 to 500 parts by weight of REHMANNIAE RADIX PREPARAT, 50 to 500 parts by weight of CINNAMOMI CORTEX, 50 to 500 parts by weight of safflower (CARTHAMI FRUCTUS), licorice (GLYCYRRHIZAE RADIX) 10 to 200 parts by weight, LYCII FRUCTUS 50 to 500 parts by weight, DIPSACI RADIX 100 to 500 parts by weight, CERVI CORNU 100 to 500 parts by weight, SALVIAE MILTIORRHIZAE RADIX 20 to 200 parts by weight , Sansa (CRATAEGII FRUCTUS) 10 to 200 weight , 10-200 parts by weight of scorching radish RADIX, 100-500 parts by weight of motherwort (LEONURI HERBA), 50-500 parts by weight of MASSA MEDICATA FERMENTATA, 50-500 parts by weight of SOJAE SEMEN, red beans (PHASEOLI SEMEN) ) A pharmaceutical composition containing 10 to 200 parts by weight of the extract thereof as a main ingredient, and extracting with a solvent selected from at least one auxiliary drug selected from or water, lower alcohol, ethyl acetate, aromatic hydrocarbon or chlorinated hydrocarbon thereof. And osteoporosis, rheumatoid arthritis and disc symptoms, formulated in the form of a pharmaceutically acceptable pharmaceutical formulation together with pharmaceutically conventionally acceptable excipients, adjuvants, diluents, isotonic agents, preservatives, suspending agents, and dissolution aids. It is to provide a pharmaceutical formulation having an excellent effect on the prevention and treatment of medicament.

In addition, the pharmaceutical formulation of the present invention is already used as an agent (allendrate), tamoxifen (tamoxifen), vitamin B ₃ , parathyroid hormone (PTH), sulfasalazine (sulfasalazine), thioredoxin reductase (thioredoxin reductase), allendronate (alendronate), raloxifene, calcitonin (calcitonin), estradiol, estradiol, genistein, 1,25-dihydroxyvitamin D ₃ , alendronate, It may further contain one or more drugs selected from estrogen receptor modulators, biphosphonates, harpagide (the drug we have developed for use).

The herbal ingredients may be powdered, or each may be extracted alone to obtain an extract, and these extracts may be mixed, or the necessary herbal ingredients may be combined and extracted together.

Figure 1 shows a method for recovering the dry weight of the pharmaceutical composition according to the extraction process of the effective drug.

Figure 2 shows the anti-inflammatory effect when inducing edema through the water extract as an effective drug.

3A and 3B show the morphological changes of the synovial membrane cells and the RAW 264.7 cell line through the water extract as an effective drug using a polarizing microscope (X 200).

Figure 4 is a graph showing the inhibition of COX-II production in the transcription step by stimulating LPS to Raw264.7 cell line through the water extract as an effective drug.

Figure 5 shows the effect on the cell cycle through the effective drug water extract.

FIG. 6 shows that the compound identified as the active ingredient of the pharmaceutical composition induces the inhibitory effect of COX-II of intramucosal synovial cells, and the cells are labeled with a secondary antibody, FITC, and then shaded with foil. After standing for some time, it was observed under a fluorescence microscope.

Figure 7 shows the osteoporosis prevention and treatment effect from ovarian extraction rats through the water extract as an effective drug (x200, phase contrast microscope).

Figure 8 shows the improvement of the disk is almost lost after treatment in patients with the disk eluted through the water extract as an effective drug through CT imaging.

Figure 9 is a bar graph showing the statistical treatment for the treatment improvement effect after treatment in patients with bone disease.

Figure 10 shows the improvement of the disk is almost lost after treatment in patients with the disk eluted through MRI imaging.

Next, the present invention will be described in more detail with reference to Examples and Experimental Examples, which do not limit the scope of the present invention.

Example 1

50g of Ojeolgol, 400g of Tofu, 500g of Ogapi, 450g of 100g of old plate, 450g of Gobi, and 500g of distilled water (or purified water) were mixed in distilled water (or purified water) in a volume of 2 to 5 times, and heated under reflux for 6 hours, followed by filtration to prepare a filtrate. Concentrated to 200ml and then lyophilized to obtain a freeze-drying weight of about 300g (hereinafter CP water extract) (Fig. 1).

Water extract obtained in the series of drying process as described above has osteoporosis, rheumatoid arthritis and anti-inflammatory activity effects as described below, respectively, water extract can be used as an active ingredient in the composition of the present invention.

Example 2

Ogolgol 100g, Ogapi 250g, tofu 200g, hyssop 240g, old plate 140g, fern 500g, windproof 100g, malt 100g, Angelica 150g, wolfberry 120g and safflower 100g in the same manner as in Example 1 to obtain X.

Example 3

Ojakgol 100g, Ogapi 200g, Tofu 200g, Umbrella 400g, Old plate 100g, Gobi 500g, Windproof 100g, Broiler 100g, Wolfberry 100g, Medicinal beans 100g and Safflower 100g in the same manner as in Example 1 to obtain X.

Example 4

Ojeolgol 100g, Ogapi 200g, tofu 200g, hyssop 400g, old plate 100g, Gobi 500g, windproof 100g, broiler 100g, wolfberry 100g, medicinal soybeans 100g and safflower 100g is extracted with 70% ethanol and the solvent is removed to obtain an ethanol extract.

Example 5

Ogigol 150g, Gugong 150g, Ogapi 150g, Tofu 200g, Root 300g, Gobi 400g, Windproof 50g, Angelica 50g, Malt 50g, Sookjihwang 50g, Broiler 100g, Safflower 100g, Licorice 50g, Sok 50g, Hyunsam 50g, Motherwort 50g, Red bean 50 g is extracted with water by the method of Example 1 to obtain X.

Example 6

Ogigol 150g, Gugong 150g, Ogapi 150g, Tofu 200g, Root 300g, Gobi 400g, Windproof 50g, Angelica 50g, Malt 50g, Sookjihwang 50g, Broiler 100g, Safflower 100g, Licorice 50g, Sok 50g, Hyunsam 50g, Motherwort 50g, Red bean 50 g are powdered to obtain a powder.

Example 7

Powder is obtained by pulverizing 50g of Ojeolgol, 400g of Tofu, 500g of Ogapi, 450g of 100g of old plate, and 500g of Gobi.

Experimental Example 1

Edema Inhibitory Effect of Arthritis

In order to observe the edema inhibitory effect of the pharmaceutical composition of the present invention in order to induce edema in 6 rats of 200g body weight per experimental group, 0.5ml of ZYMOSAN-A (20mg / ml / KG) and 0.5ml of Freund's Adjuvant After the mixture was injected into the left foot, the progress of edema was observed for 70 days. Photographs were taken before and after the induction of edema, and the water extract was prepared to be 0.6 mg / ml. The oral administration of edema was used to investigate chronic / acute suppression of edema. As a result, the control group induced edema from day 4 and reached about 30 days to reach the highest peak, while it took 45 days. It was observed that the water extract decreased after 7 days to suppress the edema (Fig. 2).

Experimental Example 2

Influence on Inhibition of Inflammation

In order to identify the active ingredient used as an active ingredient in the composition of the present invention, the morphological changes of the water extract obtained according to the method of the present invention are identified from the raw 264.7 cell line, which is a synovial membrane cell and inflammation-related cells important for inflammation of the joint. In order to confirm the cell morphological changes by dispensing 10 ⁴ cells into 6 wells and incubating them at 37 ° C. in a 5% CO ₂ INCUBATOR, the cell morphological changes were shown to be suppressed rather than cell proliferation and induced cell death. Could be (Figures 3a, b).

Experimental Example 3

Confirmation of COX-II Protein Expression by RT-PCR Analysis

In order to determine the effect on the water extract obtained according to the method of the present invention on the inhibition of COX-2 expression, which is an indicator protein of rheumatoid arthritis, cells were washed twice with PBS as described above, and then RNA zol solution was added thereto. After separating the nucleic acid and protein in the cell and centrifuged for 15 minutes at 15,000 rpm, add supernatant and 200µl of isopropanol and mix and leave for 15 minutes in the refrigerator-20 ℃, centrifuged to separate the total RNA and RT After PCR, 1% agarose gel was found to induce expression in the control group, negative control group and organ extract (lane 1, 2, 4), whereas the expression was suppressed in the water extract and old water extract groups. It can be seen (lane 3, 5) (Fig. 4).

Experimental Example 4

In order to observe the effect on the cell cycle, the obtained extract was divided into 10 ²⁶ cells of a macrophage cell, Raw 264.7 cell line, in a 60 mm culture dish, incubated for one day, and washed with PBS to obtain LPS of 50 ng / ml. After dispensing in a dish and stimulating for 2 hours, the final concentration of water extract was added to 25 ㎍ / ml, the supernatant was removed, washed with PBS, treated with trypsin, collected and put into 1.5ml eppendorf tube, and then at 2,000 rpm. The supernatant was removed by centrifugation for 5 minutes, and then fixed by adding 1 ml of 100% EtOH. At this time, 5 μg / ml propidium iodide and RNAse were mixed and prepared, and the fixed cells were centrifuged to remove the supernatant and then washed once with PBS. At the same time, the dye is added to the immobilized DNA and warmed in a thermostat at 37 ℃. As a result, the stained cells were sealed in foil and stored at 4 ° C. and subjected to flow cytometry analysis. The analyzer was FACscan (BectonDicknson, CA). As a result of the analysis, the G0 / G1 level was relatively high in the G0 / G1, S, and G2 / M stages, whereas the G0 / G1 phase stopped in the drug group and saline extract, which induced cell death as in Experimental Example 2. It can be seen that the same as (Fig. 5).

Experimental Example 5

Inhibition of COX-II Expression by Immunocytochemistry

In order to investigate whether the compound identified as the active ingredient of the pharmaceutical composition isolated according to the present invention induces the inhibitory effect of COX-II of intramucosal synovial membrane cells, the cells were cultured on a medium containing penicilin / streptomycin in 5% DMEM medium. 10 ⁴ cells were dispensed in a 6 well culture dish containing a slim cover glass and incubated at 37 ° C. for 24 hours. The extract was added to 10 ㎍ / ml and the reaction was observed. After washing with PBS, the cells were fixed on the cells with metanol, and then washed with PBS. After washing with PBS, labeled with the primary antibody COX-II, it was left at 4 ° C. for about 1 hour and the secondary antibody phosphor (fluorescein isothiocyanate: FITC) was labeled and shaded with foil and left for about 1 hour and observed under a fluorescence microscope. COX-II was not expressed in the normal group, but the control group was decreased in expression. While inducing drug treated group was expressed relative to Al inhibited (FIG. 6).

Experimental Example 6

Osteoporosis Suppression in Ovarian Extracted Rats

In order to observe the inhibitory effect on osteoporosis, the ovaries were removed from the females of 200g body weight, and the daily dose was 500 mg / ml, followed by oral administration to confirm the progress of 4 weeks. Demineralized and parrafin-embedded blocks were prepared and cut to 5㎛ in the microtome and observed with a phase contrast microscope at 100 magnification by hematoxylin / eosin staining. The drug group showed the same recovery or improvement effect as the normal group, while being slightly around the growth plate (Fig. 7).

Experimental Example 7

Improvement of disk through CT imaging

In order to investigate the clinical pharmacological effects on the series of active effects according to the present invention, the water extract obtained according to the method of the present invention was taken through an example in which a disc flowed to a disc patient, and then a CT scan was performed after treatment. As a result, as shown in FIG. 8, the disk was almost lost. Therefore, the present results and pharmacological action and confirming the substantial therapeutic effect of patients with bone disease, the water extract proved to have a beneficial treatment and prevention effect on bone disease (Fig. 8). In order to confirm the statistical significance, the results of randomized phone surveys were randomly analyzed after the CT scan and the psychological and activity of the patient. It has been demonstrated that water extract has beneficial therapeutic and prophylactic effects on bone disease (FIG. 9).

Experimental Example 8

Statistical processing on the improvement effect of disk

In order to investigate the clinical pharmacological effects, water extracts were taken from the disc patients with a case of disc flow, followed by CT scan after treatment. At the time of recording, there was a therapeutic effect such that there was no trace of disk rupture (FIG. 10).

As confirmed from the above experimental results, the novel composition of the present invention has excellent pharmacological effect. Therefore, the composition of the present invention can be usefully used as a pharmaceutical composition. The pharmaceutical composition of the present invention may vary depending on the sex, age, degree of disease, etc. of the patient, but if the composition of the present invention is used without extracting the composition of the present invention with water or an organic solvent, 1.0 g to 50 g per day is used. If used in the form of X, 10mg to 1000mg per day can be administered once to several times per day.

Compounds of the present invention are already used as an agent for osteoporosis, arthritis and ruptured discs, allenrate, tamoxifen, vitamin B ₃ , parathyroid hormone (PTH), sulfasalazine (sulfasalazine) ), Thioredoxin reductase, alendronate, raloxifene, calcitonin, calcitonin, estradiol, genistein, 1,25-dihydroxyvitamin D ₃ , may be used in combination with drugs such as alendronate, estrogen receptor modulators, biphosphonates, harpagide (the drug for which the inventors have developed their use), and the like.

By using the compound of the present invention and the above drug, it is possible to reduce the normal dose of the existing drug, thereby reducing the problems with the existing drugs.

The compounds of the present invention may be mixed with excipients, adjuvants, analgesics, isotonic agents, preservatives, and other pharmaceutically acceptable adjuvants, which are commonly used pharmaceutically, and formulated into pharmaceutically acceptable formulations for pharmaceutical purposes. Suitable formulations may be prepared. Such pharmaceutical preparations may be formulated into injections, solutions, tablets, capsules, powders, syrups and the like.

Next, the present invention will be described in more detail as formulation examples.

Formulation Example 1

Water extract 500mg of Example 1

Appropriate sterile distilled water for injection

pH adjuster

500 mg of Example 1 was dissolved in distilled water for injection, adjusted to pH about 7.6 with a pH adjuster, and then the total amount was 2 ml, and then filled in a 2 ml ampoule and sterilized to prepare a medicinal needle injection.

Formulation Example 2

500 mg of water extract powder of Example 2

Appropriate sterile distilled water for injection

pH adjuster

500 mg of Example 1 was dissolved in sterile distilled water for injection, adjusted to pH 7.2 with a pH adjuster, the whole was made to 2 ml, and then filled in an ampoule of 2 ml to prepare a medicinal needle injection.

Formulation Example 3

500 mg of water extract powder of Example 1

Lactose 100mg

Starch 100mg

Magnesium stearate proper amount

The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.

Formulation Example 4

500 mg of water extract powder of Example 1

Lactose 100mg

Starch 50mg

Magnesium stearate proper amount

The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.

Formulation Example 5

500 mg of water extract powder of Example 1

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, the inside is filled with a polyethylene coated coated chloride and sealed to prepare a powder.

Formulation Example 6

X 500mg of Example 1

Lactose 50mg

Starch 50mg

Talc 2mg

Magnesium stearate appropriate amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Formulation Example 6

X powder 500 mg of Example 1

Lactose 100mg

Starch 93mg

Tackle 2mg

Magnesium stearate proper amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Formulation Example 7

X 5g of Example 1

20 g of sugar

20 g of isomerized sugar

Lemon flavor

Add 100 ml of purified water

The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml of brown bottle and sterilized to prepare a liquid.

Formulation Example 8

Example 5 x 5 g

20 g of sugar

20 g of isomerized sugar

Lemon flavor

Add 100 ml of purified water

The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml of brown bottle and sterilized to prepare a liquid.

Formulation Example 9

X 500mg of Example 1

Alenate 10mg

Proper sterile distilled water for injection

pH adjuster

X 500 mg of Example 1 was dissolved in distilled water for injection, adjusted to pH about 7.6 with a pH adjuster, and then the total amount was 2 ml, and then filled into 2 ml ampoules and sterilized to prepare an injection.

Formulation Example 10

X 500mg of Example 1

Tamoxifen 10mg

Appropriate sterile distilled water for injection

pH adjuster

X 500 mg of Example 1 was dissolved in sterile distilled water for injection, adjusted to pH 7.2 with a pH adjuster, and the whole was made to 2 ml, and then filled in a 2 ml ampoule to prepare an injection.

Formulation Example 11

X 500mg of Example 1

20 mg sulfasalin

Lactose 100mg

Starch 100mg

Magnesium stearate proper amount

The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.

Formulation Example 12

X 500mg of Example 1

Alendronate 50mg

Lactose 100mg

Starch 50mg

Magnesium stearate proper amount

The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.

Formulation Example 13

X 500mg of Example 1

Lactose 50mg

Starch 50mg

Talc 2mg

Magnesium stearate appropriate amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Formulation Example 14

X 1000mg of Example 1

Raloxifene 10mg

Lactose 50mg

Starch 50mg

Talc 2mg

Magnesium stearate appropriate amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Formulation Example 14

X 100mg of Example 1

Pamideronic disodium 20mg

Lactose 100mg

Starch 93mg

Tackle 2mg

Magnesium stearate proper amount

The capsules are prepared by mixing the above components and filling gelatin capsules according to a conventional method for preparing capsules.

Formulation Example 16

X 1000mg of Example 1

Pamideronide Disodium 1000mg

20 g of sugar

20 g of isomerized sugar

Lemon flavor

Add 100 ml of purified water

The above components are mixed according to a conventional method for preparing a liquid, and filled into 100 ml of brown bottle and sterilized to prepare a liquid.

As described in detail above, SEAPIAE OS, EUCOMMIAE CORTEX, ACANTHOPANACIS CORTEX, Gupan (or Grow: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX), Umbrella (ACHYRANTHIS BIDENTATAE RADIX) and Gobi II : Contains powder or extract of CIBOTIUM BAROMEZ (L.) As main ingredient, if necessary, HORDEI FRUCTUS GERMINIATUS, REHMANNIAE RADIX PREPARAT, CINNAMOMI CORTEX, Safflower (CARTHAMI FRUCTUS), Licorice (GLYCYRRHIZAE RADIX), Goji (LYCII FRUCTUS), DIPSACI RADIX, Greenery (CERVI CORNU), Salvia (SALVIAE MILTIORRHIZAE RADIX), Sansa (CRATAEGII FRUCTUS) Containing at least one auxiliary drug selected from MASSA MEDICATA FERMENTATA, SOJAE SEMEN and PHASEOLI SEMEN or a solvent selected from water, lower alcohol, ethyl acetate, aromatic hydrocarbons and chlorinated hydrocarbons thereof. Relic has an excellent effect on the prevention and treatment of osteoporosis, rheumatoid arthritis, disc symptoms.

Claims (5)

SEPIAE OS, EUCOMMIAE CORTEX, ACANTHOPANACIS CORTEX, Gupan (or Growing up: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX), Ussel (ACHYRANTHIS BIDENTATAE RADIX) and Gobi (Gibu: CIBOTII RUMIZOMA A composition having an excellent effect on the prevention and treatment of osteoporosis, rheumatoid arthritis and disc symptoms, powdered (L.)) or extracted with a solvent selected from water, lower alcohols, ethyl acetate, aromatic hydrocarbons, and chlorinated hydrocarbons. SEPIAE OS, EUCOMMIAE CORTEX, ACANTHOPANACIS CORTEX, Gupan (or Growing up: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX), Ussel (ACHYRANTHIS BIDENTATAE RADIX) and Gobi (Gibu: CIBOTII RUMIZOMA (L.)) or extract extracted with water, lower alcohol, ethyl acetate, aromatic hydrocarbon, chlorinated hydrocarbon, as a main component, and if necessary, HORDEI FRUCTUS GERMINIATUS, REHMANNIAE RADIX PREPARAT, Broiler (CINNAMOMI CORTEX), safflower (CARTHAMI FRUCTUS), licorice (GLYCYRRHIZAE RADIX), wolfberry (LYCII FRUCTUS), DIPSACI RADIX, green tea (CERVI CORNU), dansam (SALVIAE MILTIORRHIZA, Sansam Risa (SCROPHULARIAE RADIX), at least one supplementary herb selected from LEONURI HERBA, MASSA MEDICATA FERMENTATA, SOJAE SEMEN, red bean (PHASEOLI SEMEN) or its water, lower alcohol, ethyl acetate, aromatic hydrocarbon, chlorination carbonization Osteoporosis containing X, extracted with a solvent selected from the bovine, of rheumatoid arthritis, compositions that are highly effective in the prevention and treatment of symptoms disk. 10-200 parts by weight of SEOPIAE OS, 50-500 parts by weight of EUCOMMIAE CORTEX, 50-500 parts by weight of ACANTHOPANACIS CORTEX, 50-500 parts by weight of an old plate (or growth: TESTUDINS PLASTRUM OR TRIONYCIS CARAPAX) , 50 to 500 parts by weight of cow's teeth (ACHYRANTHIS BIDENTATAE RADIX) and 50 to 500 parts by weight of gobi (civotii RHIZOMA: CIBOTIUM BAROMEZ (L.)) Or its extract as a main ingredient, if necessary, malt (HORDEI) FRUCTUS GERMINIATUS) 10 to 200 parts by weight, 50 to 500 parts by weight of REHMANNIAE RADIX PREPARAT, 50 to 500 parts by weight, CINNAMOMI CORTEX, 50 to 500 parts by weight of safflower (CARTHAMI FRUCTUS), licorice (GLYCYRRHIZAE RADIX) 10 to 200 parts by weight 200 parts by weight, LYCII FRUCTUS 50 to 500 parts by weight, DIPSACI RADIX 100 to 500 parts by weight, CERVI CORNU 100 to 500 parts by weight, SALVIAE MILTIORRHIZAE RADIX 20 to 200 parts by weight, hawthorn (CRATAEGII FRUCTUS) 10 to 200 parts by weight, Hyunsam (SCROPHULARI) AE RADIX) 10 to 200 parts by weight, 100 to 500 parts by weight of LEONURI HERBA, 50 to 500 parts by weight of MASSA MEDICATA FERMENTATA, 50 to 500 parts by weight of SOJAE SEMEN, 10 to 10 parts by PHASEOLI SEMEN One or more supplementary herbs selected from 200 parts by weight or water, lower alcohols, ethyl acetate, aromatic hydrocarbons, chlorinated hydrocarbons containing X extracted with a solvent selected for its excellent effect in the prevention and treatment of osteoporosis, rheumatoid arthritis, disc symptoms Composition. Osteoporosis formulated in the form of a pharmaceutically acceptable pharmaceutical formulation of the composition of claim 1 together with pharmaceutically conventionally acceptable excipients, adjuvants, diluents, isotonic agents, preservatives, suspending agents, dissolution aids, Pharmaceutical preparations with excellent effects in the prevention and treatment of rheumatoid arthritis and disc symptoms. The method of claim 4, wherein the drug is already used as an allenrate, tamoxifen, vitamin B ₃ , parathyroid hormone (PTH), sulfasalazine, thioredoxin reductase, or thioredoxin reductase. ), Alendronate, raloxifene, calcitonin, calcitonin, estradiol, genistein, 1,25-dihydroxyvitamin D ₃ , alendronate, estrogen receptor modulator (etrogen receptor modulator), biphosphonates, harpagide (harpagide is a drug that the inventors developed the use) further contains one or more drugs, and pharmaceutically acceptable Osteoporosis, which is formulated in the form of a pharmaceutically acceptable pharmaceutical formulation with excipients, adjuvants, diluents, isotonic agents, preservatives, suspending agents, and dissolution aids. Pharmaceutical formulations have excellent effects in the prevention and treatment of arthritis and tooth disc symptoms.