KR20080051893A - Pharmaceutical composition for treating and preventing gastrointestinal diseases comprising herb extracts - Google Patents

Abstract

A pharmaceutical composition comprising the herb extracts is provided to prevent and treat gastrointestinal diseases including gastritis, gastric ulcer and duodenal ulcer in an identical level to lansoprazole as a conventional proton pump inhibitor, and inhibit side effects. A pharmaceutical composition for treating and preventing gastrointestinal diseases comprises 30-70 wt.% of Hordei Fructus Germinatum extract, 3-20 wt.% of Piperis Nigri Fructus extract, 3-20 wt.% of Galli Stomachichum Corium extract, 3-20 wt.% of Caryophylli Flos extract, 3-20 wt.% of Piperis Longi Fructus extract, 3-20 wt.% of Borneolum Syntheticum extract and 2-15 wt.% of Menthae Herba extract which are prepared by extracting them in water at 100-150 deg. C for 1-2 hours.

Description

PHARMACEUTICAL COMPOSITION FOR TREATING AND PREVENTING GASTROINTESTINAL DISEASES COMPRISING HERB EXTRACTS}

1 is a photograph observing the degree of gastric wall treatment by hematoxylin and eosin staining the gastric tissue extracted from the rat in the test example,

Figure 2 shows the results of RT-PCR (reverse transcriptase-polymerase chain reaction) confirming the mRNA expression levels of COX (cyclooxygenase) -1 and COX-2 for gastric tissues extracted from rats in the test example.

The present invention relates to a pharmaceutical composition for treating and preventing gastrointestinal diseases, such as gastritis, gastric ulcer, duodenal ulcer, containing the herbal extract as an active ingredient.

A wide range of factors, such as genetic, physiological, environmental and mental factors, can adversely affect human gastrointestinal function. Representative gastrointestinal diseases include gastritis, gastric ulcer and duodenal ulcer. Gastritis is an inflammation of the gastric mucosa due to damage to the gastric mucosa, and gastric ulcer refers to when the damage penetrates the mucosa and invades the submucosa and the muscle layer. Duodenal ulcer refers to an ulcer in the duodenum.

In general, the production of H ⁺ through stress, chemical stimulation, and acid invasion is the main cause of gastritis induction and exacerbation. Looking at the defense mechanisms in the gastric wall, mucus cells and linear (, 形, gland-type) mucous cells produce mucus and HCO ₃ ⁻ to convert pH lowered by H ⁺ back to neutral to regenerate gastric wall cells. However, when this natural defense mechanism is broken by overexpression of H ⁺ , it is necessary to inject proton pump inhibitor (PPI) from outside. Proton pump inhibitors reduce the production of H ⁺ by blocking the proton pump from the outset, which in turn balances the natural defense mechanisms and helps the stomach wall cells regenerate.

Representative proton pump inhibitors include omeprazole and lansoprazole, which inhibit acid secretion in gastric parietal cells in the final stages, and show strong acid secretion effect, but have high possibility of recurrence and diarrhea, fever, headache and fatigue It is known that it is easy to cause side effects.

Therefore, in recent years, the development of pharmaceutical compositions containing extracts of natural substances such as herbal medicine that can treat and prevent gastrointestinal diseases without side effects are urgently required.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition containing herbal extracts, which can be usefully used for the prevention and treatment of various gastrointestinal diseases without side effects at the same level as a conventionally known proton pump inhibitor.

In order to achieve the above object, the present invention is a malt ( Hodei Fructus Germiniatus ), a hoe ( Piperis Nigri Fructus ), a glaze ( Galli Stomachichum Corium ), cloves ( Caryophyli Flos ), piri ( Piperis Longi Fructus ), the brain ( Borneolum Syntheticum ) And it provides a pharmaceutical composition for treating or preventing gastrointestinal diseases, containing the hydrothermal extract of each of the menthae ( Menthae Herba ) as an active ingredient.

Hereinafter, the present invention will be described in detail.

The pharmaceutical composition for treating and preventing gastrointestinal diseases according to the present invention is characterized by containing the hydrothermal extracts of malt, leek, sediment, clove, hair loss, brain, and peppermint as active ingredients, preferably, malt, reef, 30 to 70 wt%, 3 to 20 wt%, 3 to 20 wt%, 3 to 20 wt%, 3 to 20 wt%, 3 to 20 wt% In an amount of 2 to 15% by weight, preferably 45 to 60% by weight, 5 to 10% by weight, 5 to 10% by weight, 5 to 10% by weight, 5 to 10% by weight, 5 to 10% by weight and 3 To 7% by weight.

In addition to these extracts, the pharmaceutical composition of the present invention may be used in the present invention, such as Santalini Lignum Rubrum , Arecacatechu L. , Cyperi Rhizoma , Atractylodis Rhizoma , Zingiberis Rhizoma , Magnoliae Cortex , Dermis ( Magnoliae Cortex ). Hydrothermal extracts of Citri Pericarpium ), New Song ( Massa Medicata Fermentata ), Fruits ( Aurantii Immaturus Fructus ), Sansa ( Crataegi Fructus ), Roots ( Pueraiae Radix ), Mokku ( Aucklandiae Radix ) or Sine ( Amomum Xanthioides Wallich ), or mixtures thereof It may further contain. Based on the total weight of the composition, in the amounts of 15% to 50% by weight, preferably 27% to 37% by weight, for redwood, betel nuts, flavored fruits, extracts and health extracts, respectively; For the roots of the root, neck and sine extract can be used in the pharmaceutical composition in an amount of 10 to 40% by weight, preferably 23 to 33% by weight, respectively.

These herbal extracts used in the present invention can be prepared by hydrothermal extraction or by mixing the herbal medicine or its dried product, respectively. Specifically, the herbal medicine or its dried product is cut to an appropriate size (for example, 1 cm × 1 cm or less), and then 5 to 20 times the weight of the raw material is added thereto, and then 100 to 150 ° C. for 1 to 2 hours. Extraction is followed by filtration, concentration under reduced pressure or spray drying to obtain a liquid or solid herbal extract.

Preferably, the extraction process can be carried out under closed conditions, the herbal extract obtained can be re-extracted with hot water.

Herbal medicines used in the present invention, that is, malt, horticulture, sesame seed, cloves, essential, dragon brain, peppermint brain, rosewood, betel nut, hyangbuja, creation, health, thickening, dermis, new song, fruit room, hawthorn, brown root, throat and sign To summarize the known classification, ear cut (歸 經, means the organ entering after taking the medicinal herbs) and efficacy are shown in Table 1 below:

The combination of malt, grass, cauliflower, cloves, hair loss, cerebellum and peppermint brain hydrothermal extracts of the present invention can be usefully used in the prevention and treatment of gastrointestinal diseases such as gastritis, gastric ulcer and duodenal ulcer without side effects as extracts of natural substances.

Active ingredients such as malt, vinegar, sediment, clove, essential, cerebellum and peppermint brain extract, and as necessary, rosewood, betel nut, saengbuja, creation, health, thickening, dermis, new song, fruiting, hawthorn, brown root, neck scent or sign extract, Or mixtures thereof may be mixed with a suitable pharmaceutically acceptable carrier or excipient according to conventional methods or diluted with a diluent to prepare a pharmaceutical composition having the above functions. Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose , Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition may further include fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like.

The pharmaceutical compositions of the present invention may be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulations may be in the form of tablets, pills, powders, sachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders and the like.

The pharmaceutical compositions of the invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular. Typical daily dosages of the pharmaceutical compositions of the present invention are 10 to 300 mg / kg body weight, preferably 10 to 100 mg / kg body weight, once or several, based on a mixture of herbal extracts as active ingredients. It can be administered in divided doses. However, the actual dosage of the active ingredient can be adjusted according to the route of administration, the age, sex and weight of the patient, and the severity of the disease.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are not intended to limit the invention only.

<Example> Preparation of the herbal medicine extract of the present invention

54 g of dried malt, 8 g of hoe, 8 g of starch, 8 g of cloves, 8 g of dried hair, 8 g of cedar and 6 g of peppermint were put in 1 L of water, extracted at 120 ° C. for 2 hours, and filtered. The filtrate obtained was spray dried to obtain about 10 g of a powdered herbal extract mixture (yield: about 10%).

Test Example Observational Test for Gastritis Treatment Effect

In order to observe the gastritis treatment effect of the herbal extracts of the present invention, a comparative test of gastritis treatment effect when administered orally using rats was performed as follows. In this test, the medicinal herb extract mixture obtained in the above example was used as a test drug, lansoprazole (Samil Pharmaceutical Co., Ltd.), which is well known as a proton pump inhibitor, and distilled water was used as another group.

Sprague-Dawley male rats (180-200 g body weight, 6 weeks old) were used in each of 7 rats. Rats were reared for 5 days (120 hours) in the same condition cages to induce gastritis by freely ingesting 0.1% iodoacetamide with water (average daily intake per experimental group = approximately 2.6 g). After 5 days, one dog in each group was confirmed to cause gastritis by necropsy, and rats were immediately used for the test. 50 mg / kg of the test drug, 5 mg / kg of the control drug, or an appropriate amount of distilled water were orally administered to the rat using an oral administration device per kg of rat body weight. The doses of the test drug and the control drug were applied by converting the appropriate doses that can be used in the clinic to the rat, and administration was performed four times, immediately after 24 hours, 48 hours, and 69 hours after the 5th day of gastritis. .

In the case of Test Example (1), rats were fasted for 24 hours after the last drug administration, and then Chacool mill (Charcoal meal, 10% Chacool + 10% Tragacanth) was administered to Sonde. Rats were sacrificed 1 hour after administration of the Chacool Mill. In the following Test Examples (2) to (4), rats were sacrificed 3 hours after the last administration of the drug.

(1) prokinetic action ratio

For the sacrificed rats, the chacool mill travel distance and the length from the pyloric to the cecum were measured, respectively, and the gastrointestinal motility activity was determined by Equation 1 below. The gastrointestinal motility activity results of the three groups administered with distilled water, control drug (lansoprazole) and test drug (the herbal extract mixture of the present invention) after gastritis induction are shown in Table 2 below:

Gastrointestinal motility rate (%) = (charcoal wheat travel) / (length from pyloric to cecum) x 100

From Table 2, it can be seen that the administration of the control drug and the test drug showed higher gastrointestinal activity rate than the case of administration of distilled water after gastritis induction, and the result was statistically processed through SPSS 12.0 for Windows. The results of the post-test were found to be significant at the 95% confidence level (P <0.05).

(2) lesion score ratio

After the stomach was removed from the rat, the degree of damage (area) of the gastric wall was measured using IMT iSolution DT version 7.5 (IMT-iSolution Inc.), and the incidence of lesions was determined by Equation 2 below. The incidence of foci incidence measured for the three groups administered distilled water, control agent (lansoprazole) and test drug (herbal extract mixture of the present invention) after gastritis induction are shown in Table 3 below:

Incidence (%) = (Stomach Damage Area) / (Total Stomach Surface Area) × 100

From Table 3, it can be seen that the administration of the control drug and the test drug, respectively, compared to the case of administration of distilled water after gastritis, showed a lower incidence rate, that is, a higher treatment effect on the window, and the result was SPSS for windows. Statistical processing and post-test through 12.0 revealed that only the test drug was significant at the 95% confidence level (P value <0.05).

(3) Hematoxylin and eosin tissue staining

Gastric tissue extracted from the rat was cut to a thickness of 30 μm and stained with hematoxylin and eosin to observe the degree of gastric wall treatment, and the results are shown in FIG. 1. In FIG. 1, (a) shows that gastritis is not induced (normal rats), and (b) to (d) are respectively administered distilled water, control drug (lansoprazole), and test drug (medicinal herb extract mixture of the present invention) after gastritis is induced. In the case indicated.

From the photograph of Figure 1, it can be seen that the damaged gastric wall (b) was treated in a state similar to that before inducing gastritis by administering the test drug (d) and the control drug (c).

(4) RT-PCR (Reverse Transcription Polymerase Chain Reaction)

For gastric tissue extracted from rats, the house gene β-actin (action) was quantitatively confirmed, and then mRNA expressions of COX (cyclooxygenase) -1 and COX-2, which are major genes related to inflammation, were identified. The amount was confirmed and shown in FIG. The sequences and reaction conditions of the primers used for RT-PCR are as follows:

β-actin

Sense: SEQ ID NO: 1

Antisense: SEQ ID NO: 2

PCR reaction product: 514bp

Reaction conditions: The amplification was carried out through 28 cycles as follows: denature 94 ° C 45s, annealing 59.3 ° C 45s and extension 72 ° C 1min

COX-1 and COX-2

COX-1 Sense: SEQ ID NO: 3

COX-1 antisense: SEQ ID NO: 4

COX-1 PCR reaction product: 167 bp

COX-2 Sense: SEQ ID NO: 5

COX-2 antisense: SEQ ID NO: 6

COX-2 PCR product: 214bp

Reaction conditions: The amplification was carried out through 30 cycles as follows-denaturation 94 ℃ 30s, annealing 53.5 ℃ 30s and extension 72 ℃ 45s.

In FIG. 2, (a) shows that gastritis is not induced (normal rats), and (b) to (d) respectively, distilled water, control drug (lansoprazole), and test drug (medicinal herb extract mixture of the present invention) after gastritis are induced. In the case indicated.

From the results of FIG. 2, COX-1 is a gene that exists even in a normal state, whereas a certain amount of bands are formed, whereas COX-2 shows a marked difference according to the treatment method after gastritis induction. The large expression of COX-2 gene means that gastritis is serious, and thus, the administration of test drug (d) and control drug (c) can significantly reduce the expression of COX-2 gene.

As described above, the composition containing the malt, poncho, sediment, clove, hair loss, brain and peppermint brain extract according to the present invention as an active ingredient corresponds to the extract of the natural substance, with little side effects, conventionally well Nearly equal to lansoprazole, a known proton pump inhibitor, it can be usefully used for the prevention and treatment of gastrointestinal diseases such as gastritis, gastric ulcer and duodenal ulcer.

<110> Korea Institute of Oriental Medicine <120> Pharmaceutical composition for treating and preventing          gastrointestinal diseases comprising herb extracts <130> FPD / 200610-0185 <160> 6 <170> KopatentIn 1.71 <210> 1 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> sense primer for beta-actin <400> 1 tgtgatggtg ggaatgggtc ag 22 <210> 2 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> antisense primer for beta-actin <400> 2 tttgatgtca cgcacgattt cc 22 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer for cyclooxygenase-1 <400> 3 gcctcgacca ctaccaatgt 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer for cyclooxygenase-1 <400> 4 aggtggcatt cacaaactcc 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer for cyclooxygenase-2 <400> 5 tacccggact ggattctacg 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer for cyclooxygenase-2 <400> 6 aagttggtgg gctgtcaatc 20  

Claims (8)

Hydrothermal extracts of malt ( Hodei Fructus Germiniatus ), poncho ( Piperis Nigri Fructus ), glaucoma ( Galli Stomachichum Corium ), cloves ( Caryophyli Flos ), piperi ( Piperis Longi Fructus ), brain ( Borneolum Syntheticum ) and peppermint ( Menthae Herba ) A pharmaceutical composition for treating or preventing gastrointestinal diseases, containing as an active ingredient. The method of claim 1, 30 to 70% by weight, 3 to 20% by weight, 3 to 20% by weight, 3 to 20% by weight, 3 to 20% by weight, and 3 to 30% of malt, reef, broth, cloves, hair, brain and peppermint A pharmaceutical composition for treating or preventing gastrointestinal diseases, characterized in that it comprises in an amount of 20% by weight and 2 to 15% by weight. The method of claim 2, Malt, vinegar, sediment, clove, hair, brain and peppermint hydrothermal extract 45 to 60% by weight, 5 to 10% by weight, 5 to 10% by weight, 5 to 10% by weight, 5 to 10% by weight, 5 to 5% A pharmaceutical composition for treating or preventing gastrointestinal diseases, characterized in that it comprises in an amount of 10% by weight and 3 to 7% by weight. The method of claim 1, The hot water extract is characterized in that obtained by extraction for 1 to 2 hours in hot water of 100 to 150 ℃, gastrointestinal disease treatment or prevention pharmaceutical composition. The method of claim 1, Rosewood ( Santalini Lignum Rubrum ), Betel ( Arecacatechu L. ), Cypressi ( Cyperi Rhizoma ), Creation ( Atractylodis Rhizoma ), Health ( Zingiberis Rhizoma ), Gak ( Magnoliae Cortex ), Dermis ( Citri Pericarpium ), New Song ( Massa Medicata Fermentata ) , to a hot-water extract, or characterized in that it contains additionally a mixture of jisil (Aurantii Immaturus Fructus), hawthorn (Crataegi Fructus), Puerariae Radix (Pueraiae Radix), elecampane (Aucklandiae Radix) or COD (Amomum Xanthioides Wallich), Pharmaceutical composition for treating or preventing gastrointestinal diseases. The method of claim 5, wherein Sandalwood, betel nut, flavor rich, creation or health extract, characterized in that it comprises 15 to 50% by weight based on the total weight of the composition, gastrointestinal disease treatment or prevention pharmaceutical composition. The method of claim 5, wherein Hakbak, dermis, singok, fruit room, hawthorn, brown root, throat, or sine extract is characterized in that it comprises an amount of 10 to 40% by weight based on the total weight of the composition, a pharmaceutical composition for treating or preventing gastrointestinal diseases. The method of claim 5, wherein The hot water extract is characterized in that obtained by extraction for 1 to 2 hours in hot water of 100 to 150 ℃, gastrointestinal disease treatment or prevention pharmaceutical composition.

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