阅读说明：本技术 用于预防或治疗丙型肝炎病毒感染疾病的药学组合物 (For preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease ) 是由 康世灿 于 2018-04-17 设计创作，主要内容包括：本发明涉及用于预防或治疗丙型肝炎病毒(Hepatitis C virus,HCV)感染疾病的药学组合物。本发明的用于预防或治疗丙型肝炎病毒感染疾病的药学组合物含有龙芽草属植物提取物及五倍子提取物,因此对人体无害,并具有有效地抑制丙型肝炎病毒的增殖的效果。(The present invention relates to the pharmaceutical compositions for preventing or treating Hepatitis C Virus (Hepatitis C virus, HCV) infectious disease.Pharmaceutical compositions for preventing or treating infection with hepatitis C virus disease of the invention contain genus Agrimonia's extract and nutgall extractive, therefore harmless, and have the effect of the proliferation for effectively inhibiting Hepatitis C Virus.)

1. a kind of for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, which is characterized in that include imperial bud Careless genus plants extract and nutgall extractive.

2. it is according to claim 1 for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, it is special Sign is that above-mentioned composition increases the autophagocytosis of liver cell.

3. it is according to claim 1 for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, it is special Sign is, by using C₁-C₄Alcoholic solvent extract above-mentioned genus Agrimonia's extract.

4. it is according to claim 1 for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, it is special Sign is, by using C₁-C₄Alcoholic solvent extract above-mentioned nutgall extractive.

5. it is according to claim 1 for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, it is special Sign is that above-mentioned genus Agrimonia is Agrimony.

6. it is according to claim 5 for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, it is special Sign is that above-mentioned Agrimony extract includes luteolin 7-O- β-D glucosiduronic acid.

7. it is according to claim 1 for preventing or treating the pharmaceutical compositions of infection with hepatitis C virus disease, it is special Sign is, mixes above-mentioned genus Agrimonia's extract and nutgall extractive with the weight ratio of 5:5 to 8:2.

8. a kind of for preventing or treating the food compositions of infection with hepatitis C virus disease, which is characterized in that include imperial bud Careless genus plants extract and nutgall extractive.

Technical field

The present invention relates to for preventing or treating to be drawn by the infection of Hepatitis C Virus (Hepatitis C virus, HCV) The pharmaceutical compositions of the disease risen.

Background technique

Hepatitis C Virus (Hepatitis C virus, HCV: hereinafter referred to as " HCV ") is mainly obtained by blood transfusion and community Sexuality dye (community-acquired) causes.If by infection with hepatitis C virus, in the case where there is its sign, about 20% develops into oxyhepatitis, and about 80% or so develops into chronic hepatitis, wherein there are about 30% to develop into cirrhosis and liver cancer. It is shown according to recent report, the whole world has about 200,000,000 people or more by infection with hepatitis C virus, just has in the U.S. by inference More than 4500000 people (highest is up to 15,000,000 people) and there are 5,000,000 people in Europe that the above are hepatitis C patients.

Up to the present, there is not yet the brilliant vaccine or effective therapeutic agent for hepatitis C, therefore in the world Many drugmakers and research institute all exploitation hepatitis C therapeutic agent.Compared with hepatitis B, hepatitis C is in full generation Boundary is evenly distributed, and is transferred to the ratio of cirrhosis or liver cancer much higher than hepatitis B.And develop into the ratio of chronic hepatitis more Height, so the research for this development mechanism is still continuing.Also, hepatitis C not only can be by blood transfusion, but also can lead to It crosses the intravenous injection of drug or tatoos to infect, but mainly infected by direct contacting blood.Once by hepatitis C virus Poison infection, Most patients will develop into chronic hepatitis, and develop into cirrhosis or liver cancer again.Therefore, compel to be essential at present Develop effective vaccine and therapeutic agent.Hepatitis C Virus has a variety of genotypes in Strain (strain) (genotype) and frequent occurrence it is mutated (mutation), in the case where the chronic hepatitis as caused by Hepatitis C Virus, lost Progress of disease abnormal shape (genetic variants) also leads to again subinfection (reinfection) while infecting (coinfection) Deng.Therefore, the effective vaccine for developing hepatitis C is difficult to be succeeded.

Currently, the treatment method as hepatitis C is implemented and uses interferon-' alpha ' (Interferon- α) and Ribavirin (Ribavirin) treatment method, but its treatment rate is very low, and side effect is very serious.In the case where interferon therapy, completely Responseless situation accounts for about 25%, occurs accounting for about 25% the case where recurrence after temporarily reacting.In remaining 50% patient, Glutamic-pyruvic transaminase (ALT) value keeps normal until treatment end and HCV RNA (RNA) becomes negative, Wherein 50% or so recurs in 3~6 months after treatment is finished, as a result only 25% or so is able to maintain that 6 months or more and controls Simultaneously there is continued viral response (sustained viral response) in therapeutic effect.Also, there are 6 kinds in Hepatitis C Virus Genotype (genotype), but the most 1b type of South Korea is not so good as to the reaction of interferon therapy and 2 types, 3 types.Based on above-mentioned original Cause, with Ribavirin and the used time, but in the case, therapeutic effect can improve 2 times or so, but be used alone several when Ribavirin It is invalid, and red blood cell is destroyed, and leads to the side effects such as anaemia occur, thus mainly in interferon therapy without reaction or It prescribes in the case where recurrence.Therefore, up to the present, not yet exploitation plays special role to Hepatitis C Virus, inhibits its increasing It grows, can effectively treat the antiviral drugs of hepatitis C.

There is therapeutic effect or to common liver cell with known to protecting effect to virus infection as in natural plants Ingredient has glycyrrhizin (glycyrrhizin), catechin (catechin), silymarin (silymarin) etc., it was reported that on It states ingredient to be although able to suppress the duplication of hepatitis virus and have the function of outstanding Liver protection, but fails exploitation into therapeutic agent (Altern Med Rev 1999Aug；4 (4): 220-38, Zhongguo Zhong Xi Yi Jie He Za Zhi1992Aug；12).

Therefore need to develop Small side effects and the outstanding Hepatitis C Virus therapeutic agent of therapeutic effect.

Summary of the invention

Technical problem

The present invention proposes to solve the above-mentioned problems, provides the autophagocytosis by increasing liver cell effectively to prevent Or the pharmaceutical compositions for the treatment of infection with hepatitis C virus disease.

Solution to problem

In the present invention embodiment appropriate, for preventing or treating the pharmaceutical compositions of hepatitis c virus infection disease It is characterized in that, includes Long Yacao genus plants extract and nutgall extractive.

Also, pharmaceutical compositions of the invention are characterized in that, increase the autophagocytosis of liver cell.

Also, pharmaceutical compositions of the invention are characterized in that, by using C₁-C₄Alcoholic solvent extract above-mentioned imperial bud Careless genus plants extract.

Also, pharmaceutical compositions of the invention are characterized in that, by using C₁-C₄Alcoholic solvent extract above-mentioned five times Seed extract.

Also, pharmaceutical compositions of the invention are characterized in that, it is preferable that above-mentioned genus Agrimonia is Agrimony (Agrimonia pilosa L.), above-mentioned Agrimony extract include luteolin 7-O- β-D glucosiduronic acid (luteolin7- O-beta-D glucuronide)。

Also, pharmaceutical compositions of the invention are characterized in that, mix above-mentioned Agrimony category with the weight ratio of 5:5 to 8:2 Plant extracts and nutgall extractive.

In another embodiment appropriate of the invention, for preventing or treating the food of infection with hepatitis C virus disease Product composition is characterized in that, includes genus Agrimonia's extract and nutgall extractive.

The effect of invention

Pharmaceutical compositions for preventing or treating the infectious disease as caused by Hepatitis C Virus of the invention contain dragon Wheatgrass genus plants extract and nutgall extractive, thus it is harmless, and effectively inhibit Hepatitis C Virus The effect of proliferation.

Detailed description of the invention

Fig. 1 is the autophagy inducing effect for comparing genus Agrimonia.

Fig. 2 shows Europe agrimony (Agrimonia eupatoria L.) and Agrimony (Agrimonia pilosa L.) ultraviolet-visible light (UV-vis) spectrum of extract (is above Agrimony extract spectrum, mentions below for Europe agrimony Take the spectrum of object).

Fig. 3 shows the autophagy inducing effect of nutgall extractive.

When Fig. 4 is preparation Agrimony (Agrimonia pilosa L.) extract, certainly according to the induction of concentration of alcohol performance Bite activity.

Fig. 5 is shown according to being mixed with mentioning for Agrimony (Agrimonia pilosa L.) extract and nutgall extractive Take the autophagy inducing effect of mixture weight ratio.

Fig. 6 is compared according to Agrimony (Agrimonia pilosa L.) extract and nutgall extractive and is extracted mixed Close the autophagy inducing effect of the time of object.

Fig. 7 is inhibition efficiency of the extraction mixture of the present invention to Hepatitis C Virus.

Specific embodiment

The present invention described further below.Before this, it is used in specification of the invention and the claimed range of invention Term or word be not necessarily to be construed as limitation usually or dictionary meanings, inventor is in order to illustrate oneself hair with the best way It is bright, based on the principle that can suitably define term concepts, should be interpreted to meet the meaning and concept of technical idea of the invention. Therefore, the structure for being recorded in this specification embodiment is only the most preferred embodiment of the present invention, is not represented of the invention complete Portion's technical idea, it is to be understood, therefore, that also there are a variety of equivalent technologies that can replace these in the application angle Scheme and variation.

Pharmaceutical compositions for preventing or treating infection with hepatitis C virus disease of the invention are characterized in that, include Agrimony, which belongs to, plants extract and nutgall extractive.

Agrimony used in the present invention is the perennial grass in growth mountain out of office or field, have Agrimony, hairyvein agrimony, A variety of titles such as sweet vernal grass, fortune silene herb with root.With in the civil example as hemostat or antidiarrheic, also have as gastric ulcer, intestines The example of scorching, kidney and arthritis treatment.In particular, some species for belonging to Agrimony category had been used for anticancer and were immunized in the past It adjusts.The agrimonine (Agrimonin) of one of genus Agrimonia's ingredient is the tannin ingredient with immunoregulation effect, also Antitumaous effect is played by induction interleukin 1.

Also, Chinese gall used in the present invention is by Chinese sumac (Rhus javanica L.) or other congeners Anacardiaceae (Anacardiaceae) leaf on Gallnut Aphid (Melaphis chinensis Bell) stab and give birth to At worm nest, wherein 50~70% be galla turcica tannins, gallic acid, Penta-O-galloyl-D-glucopyranose (pentagalloyl It glucose) is main component.

Pharmaceutical compositions of the invention include genus Agrimonia's extract and nutgall extractive, enhance liver cell oneself The effect of biting.Autophagy (autophagy, autophagy) is that a kind of natural decomposition in adjustment process is unnecessary or without function The failure mechanism of cellular component, pharmaceutical compositions of the invention can be prevented by increasing or inducing above-mentioned autophagy or be treated by third Disease caused by Hepatitis virus infects.

The disease as caused by above-mentioned infection with hepatitis C virus may include the hepatitis C as caused by Hepatitis C Virus, can By this hepatitis C state liver fibrosis, cirrhosis and the liver caused by Hepatitis C Virus that gradually chronicity develops Cancer, but it is not limited to this, can be the whole diseases caused by infection with hepatitis C virus.

On the other hand, above-mentioned genus Agrimonia's extract can be obtained according to well known plant extraction process, it is preferable that can It is extracted using organic solvent.

As an example for the preparation genus Agrimonia's extract for using organic solvent, organic solvent can be used to extract imperial bud Careless platymiscium simultaneously removes water-soluble fraction, to obtain organic solvent fraction.As another example, extracted using organic solvent After the herb of plant, by processing water-insoluble organic solvent come Separation of Organic fraction and water-soluble fraction, then, With water-insoluble organic solvent treatment of water-soluble fraction, to can get each fraction and water-soluble fraction.

Preferably, the organic solvent used to prepare genus Agrimonia's extract of the invention may include C₁-C₄'s Alcoholic solvent may include the ethyl alcohol of 30~80 weight percent most preferably it is highly preferred that may include alcohol solvent.

Also, the type of workable genus Agrimonia may include having Europe agrimony (Agrimonia according to the present invention Eupatoria L.), Agrimony (Agrimonia pilosa L.), drag leaf Agrimony (Agrimonia coreana N), Agrimonia coreana N.for.pilosella Satake、Agrimonia gryposepala、Agrimonia rostellata、Agrimonia pubescens、Agrimonia parviflora、Agrimonia striata、 Agrimonia ordorata、Agrimonia incisa、Agrimonia polyphylla、Agrimonia microcarpa、Agrimonia bracteata、Agrimonia repens、Agrimonia platycarpa、 Any one in Agrimonia pumila and Asia Agrimony (Agrimonia asiatica), most preferably Agrimony (Agrimonia pilosa L.)

Different from other genus Agrimonias, above-mentioned Agrimony extract contains a large amount of luteolin 7-O- β-D glucose Thuja acid, because mentioned component can effectively prevent or treat disease caused by the third type virus infection.

Also, above-mentioned nutgall extractive can be obtained according to well known plant extraction process, it is preferable that can be used organic Solvent extracts.

An example of nutgall extractive is prepared as organic solvent is used, and organic solvent can be used to extract Chinese gall plant And water-soluble fraction is removed, to obtain organic solvent fraction.As another example, the complete of plant is extracted using organic solvent After grass, by processing water-insoluble organic solvent come Separation of Organic fraction and water-soluble fraction, then, use is non-aqueous Property organic solvent treatment of water-soluble fraction, to can get each organic solvent fraction and water-soluble fraction.

Preferably, the organic solvent used to prepare nutgall extractive of the invention may include C₁-C₄Alcohol it is molten Agent may include the ethyl alcohol of 30~80 weight percent most preferably it is highly preferred that may include alcohol solvent.

Further, it is possible to above-mentioned genus Agrimonia's extract and nutgall extractive are mixed with the weight ratio of 5:5 to 8:2, It is highly preferred that can be mixed with the weight ratio of 6:4 to 7:3.In the case where being more than the mixing of above-mentioned weight ratio, liver cell autophagy is living Property reduce, it is invalid to the prevention or treatment of the disease as caused by the third type virus infection.

Also, the extraction mixture of above-mentioned genus Agrimonia's extract and nutgall extractive, can be in pharmacy Effective amount is used alone, or can also be used as pharmaceutical composition administration, described pharmaceutical composition contain with it is more than one Acceptable carrier, diluent or excipient in pharmacy.Term " effectively measuring in pharmacy ", which refers to, to be enough can be applicable in The amount of the extract of disease is treated or prevented in therapeutic treatment or the reasonable benefit or Hazard ratio of prevention.But owner's mostly meeting Understand, the total daily dose of the pharmaceutical compositions comprising genus Agrimonia's extract and nutgall extractive of the invention will be by curing It is raw to be determined under reasonable medical judgment.To the specific a effective amount of horizontal according to including disease and its serious journey of particular patient Active, the used particular composition of degree, used extract；Age, weight, health, gender and the diet of patient, institute Administration time, administration route and the discharge ratio of the specific extraction object used；It is treatment time, same with used specific extraction object When the drug that uses including factor and other medical domains in the factor that knows determine.For example, those skilled in the art fill Divide the level recognized for the dosage of extract to be set below and realize required therapeutic effect, is then slowly increased until reaching institute Need effect.

Also, it can be administered by conventional approach comprising genus Agrimonia's extract of the invention and Chinese gall extraction The composite extract of object, for example, can be with the oral form of tablet, capsule, dragee or film-coated tablet, liquor or suspending agent Administration.

Composite extract of the invention is mixed with pharmaceutically acceptable carrier, diluent or excipient, to provide spy Determine the pharmaceutical composition of dosage form.Pharmaceutical compositions by conventional method come dosage form, and in the form of appropriate in pharmacy be administered.Example It such as, can be containing reactive compound and diluent (for example, lactose, glucose, sucrose, cellulose, corn form sediment in solid agent for oral use Powder or potato starch), suspending agent is (for example, silica, talcum, stearic acid, magnesium stearate or calcium stearate and/or poly- second Glycol), bonding agent (for example, starch, Arabic gum, gelatin methylcellulose, carboxymethyl cellulose or polyvinylpyrrolidone), Disintegrating agent (for example, starch, alginic acid, alginate or Explotab), dyestuff, sweetener, moistens formal mixture Agent (for example, lecithin, polysorbate, lauryl sulfate) and the materia medica inert matter for being typically used in pharmacy. These medicaments can be prepared according to well known method, such as mixing, granulating, tabletting, sugar-coat or film coating process means.

As the other modes that composite extract of the present invention is administered orally, liquid dispersion, typically, Ke Yiwei can be enumerated Syrup, emulsion or suspension.Such as natural gum, agar, sodium alginate, pectin, methyl can be contained with suspension and emulsion Cellulose, carboxymethyl cellulose or polyvinyl alcohol are as carrier.

Also, the present invention is provided comprising genus Agrimonia's extract and nutgall extractive as pair for effective component The prevention and treatment of liver disease have the food of booster action.Food compositions of the invention correspond to functional food (functional food), nutritional supplement (nutritional supplement), nutritional agents (nutrient), medicinal food Product (pharmafood), health food (health food), health care product (nutraceutical), anti-cancer food (designer Food), all forms such as food additives (food addtives).It will be understood by those skilled in the art that about the above-mentioned type Food compositions can prepare various forms in a conventional manner.For example, health food is mainly with tea, fruit juice, jelly and beverage Form it is edible, be commonly used in folkd therapy.Also, functional food can be candy, Yoghourt, biscuit, butter, artificial Huang The forms such as oil.Also, food additives can be the form of powder or concentrate.

It is described above only illustratively to describe technical idea of the invention, in the common skill of the technical field of the invention Art personnel can carry out a variety of modification and deformation in the case where not departing from intrinsic propesties of the present invention.Therefore, the present invention is public The embodiment and non-limiting technical idea of the invention opened, but in order to illustrate, and these embodiments are not intended to limit the present invention Technical idea range.Protection scope of the present invention should be protected by foregoing invention and be required to explain, and fall into this equivalency range Interior all technical ideas should be interpreted as including to be claimed in range in invention of the invention.

Hereinafter, present invention will be further described in detail through examples.Embodiment is only used for further illustrating the present invention, right It should be apparent to those skilled in the art that main idea according to the present invention, the scope of the present invention are not restricted by the embodiments.

Preparation example 1

It is separately dried Europe agrimony (Agrimonia eupatoria L.), Agrimony (Agrimonia pilosa L. it) and after dragging the herb of leaf Agrimony (Agrimonia coreana N.) crushes, is added in the crushed material of every 20kg The ethyl alcohol of 50 weight percent of 200L, 80 DEG C at a temperature of refluxing extraction 6 hours, and after being condensed into 20Brix, sprayed Mist is dry, obtains the Agrimony category extract of 1.5kg.

Preparation example 2

After the Chinese gall of acquisition one band of Jizhou Island is dried, dry Chinese gall dry in the shade frittering, crushing is frittered Chinese gall after, in the crushed material of every 20kg be added 200L 50 weight percent ethyl alcohol, after being condensed into 20Brix, carry out Spray drying, obtains the nutgall extractive of 1.5kg.

Experimental example 1

With the hepa1c1c-7 cells of mouse liver cancer cell lines (Korea Cell system library (Korea Cell Line Bank), KCLB22026) it is object, confirms the autophagy inducing effect of the extract prepared in above-mentioned preparation example 1, result such as Fig. 1 institute Show.

Referring to Fig.1, with Europe agrimony (Agrimonia eupatoria L.) extract and drag leaf Agrimony (Agrimonia coreana N.) extraction is compared, and the autophagy activity of Agrimony (Agrimonia pilosa L.) extract is more It is high.

Experimental example 2

With the Europe agrimony (Agrimonia eupatoria L.) prepared in above-mentioned preparation example 1 and Agrimony (Agrimonia pilosa L.) extract is object analysis UV-visible light (UV-vis) spectrum, result such as Fig. 2 It is shown.

Referring to Fig. 2, Europe agrimony (Agrimonia is contained in Agrimony (Agrimonia pilosa L.) extract Eupatoria L.) the extract compound that does not include, above compound is luteolin 7-O- β-D glucose as the result is shown for analysis Thuja acid (luteolin 7-O-beta-D glucuronide).

Agrimony (Agrimonia pilosa L.) extract and Europe agrimony (Agrimonia eupatoria L.) Though extract is the extract of kindred plant, had differences in terms of the ingredients such as luteolin 7-O- β-D glucosiduronic acid, because This, it is believed that autophagy activity etc. also has difference.

Experimental example 3

Fig. 3 is shown, and is with the hepa1c1c-7 cell (Korea Cell system library, KCLB22026) of mouse liver cancer cells master Object is evaluated according to the autophagy inducing effect of the extractive content (concentration) prepared in above-mentioned preparation example 2, is tied Fruit is as shown in Figure 3.

It can confirm referring to Fig. 3, nutgall extractive concentration is higher, and autophagy activity is more active.

Experimental example 4

With the main hepa1c1c-7 cell of mouse liver cancer cells (Korea Cell system library, KCLB22026) for object, to according to upper State the concentration of the Extraction solvent of Agrimony (Agrimonia pilosa L.) extract in embodiment 1 with excellent Autophagy active effect is evaluated.

It is prepared for Agrimony (Agrimonia pilosa L.) extract according to the method for preparation example 1, by by ethyl alcohol Concentration be changed to 0 weight percent, 30 weight percent, 50 weight percent, 70 weight percent, 100 weight percent come into Row extracts, and as shown in Figure 4 for the result of each extract.

Referring to Fig. 4, in the case where the ethyl alcohol using 50 weight percent prepares extract, the inducing effect of autophagocytosis It is optimal.