CN103110700A - Fraxinus mandshurica extract for treating rheumatoid arthritis - Google Patents

Abstract

The invention discloses fraxinus mandshurica extract for treating rheumatoid arthritis and belongs to the technical field of traditional Chinese medicines. The fraxinus mandshurica extract comprises the following compounds in percentage by weight: 50%-95% of fraxinol glucoside, 2%-15% of fraxin, 0.1%-1% of isoscopolin and 0.1%-1% of isofraxidin-beta-D-glucoside. The fraxinus mandshurica extract has the beneficial effects of being low in toxicity, safe and reliable in comparison with chemical medicines such as hormones and the like while being applied to the medicine for treating rheumatoid arthritis; moreover, the fraxinus mandshurica leaf resources are abundant, the waste material is changed into things of value and the extraction process is simple; the fraxinus mandshurica extract and pharmaceutically acceptable excipients or auxiliaries materials can be used for preparing a medical composition; and the medical composition can be prepared into various dosage forms such as gastrointestinal tract dosage forms consisting of tablets, pills, capsules, particles, tinctures and oral liquid as well as gastrointestinal tract external dosage forms consisting of injections, external-use preparations and the like by adopting the conventional method of the galenic pharmacy.

Description

A kind of Cortex Fraxini mandshuricae extract for the treatment of rheumatoid arthritis

Technical field

The invention belongs to the Chinese medicine technical field, relate to a kind of extraction for the treatment of the medicinal raw material of rheumatoid arthritis.

Background technology

Rheumatoid arthritis (rheumatoid arthritis) is a kind of chronic systemic autoimmune disease take articular synovitis as feature.Synovitis is outbreak repeatedly lastingly, the destruction that can cause intraarticular cartilage and bone, and joint function disturbance, even maimed.

At the end of last century rheumatoid arthritis abroad prevalence be 1% to 2%, indivedual areas are higher than 5%, China is about 0.3% to 0.45%, though lower than abroad, because China is populous, estimate that patient with rheumatoid arthritis more has 4,000,000 more than.The positive rejuvenation of patient with rheumatoid arthritis, a China of Neijiang City in Sichuan Province reported that the child who suffers from rheumatoid arthritis who accepted for medical treatment in 3 years just reached 65 examples in 2010.Rheumatoid arthritis is not only the very high disease of a kind of disability rate, but also can make patient's life-span compared with normal shorten 10 years more than, is a kind of disease of serious harm human health, is called as " not dead cancer ".Yet the rheumatoid cause of disease, pathogenesis are also indefinite so far, both also there is no the effectively preventing measure without the radical cure method.

The medicine for the treatment of atrophic diseases is main by nonsteroidal antiinflammatory drug, hormone now, assists some to improve the antirheumatic of the state of an illness.Wherein nonsteroidal antiinflammatory drug is mainly to the toxic effect of gastrointestinal tract, kidney, liver and blood system; Hormone medicine is because it is not the radical cure medicine, and long-term a large amount of uses can be brought out infection, osteoporosis, femur head necrosis, diabetes, peptic ulcer, hypertension, psychological problem etc., and easy generation state of an illness rebound phenomenon as too fast in drug withdrawal; Improve the toxic action that internal organs (liver, kidney, bladder, lung, gastrointestinal, gonad) that the antirheumatic of the state of an illness wants body weight for humans and tissue (bone marrow) are had nothing in common with each other.

Chinese medicine is used the history of existing thousands of years at home, is that China people sum up with the very rich experience that disease is struggled for a long time.The medicine of seeking a kind of high-efficiency low-toxicity for the treatment of rheumatoid arthritis from Chinese medicine is extremely urgent, and society and economic benefit are all good, have very large promotional value.

Cortex Fraxini mandshuricae (Fraxinus mandschurica Rupr.) is Mu Xi Ke Ash platymiscium, the diseases such as its bark treatment rheumatism of use among the people, rheumatoid, osteodynia, effect determined curative effect.The Cortex Fraxini mandshuricae skin once used as the succedaneum of Cortex Fraxini.Contain the chemical compositions such as coumarin, phenethyl alcohol glycosides, flavonoid, iridoid in the bibliographical information Cortex Fraxini mandshuricae, less to pharmacology activity research both at home and abroad.The inventor did systematic research to the compound in Cortex Fraxini mandshuricae, found that its chemical composition coumarin and phenethyl alcohol glycosides are main, and wherein feature coumarin kind compound fraxinol and glycosides compound mandshurin content thereof are higher.

Summary of the invention

The objective of the invention is: a kind of Cortex Fraxini mandshuricae extract for the treatment of rheumatoid arthritis is provided, and it can be used as pharmaceutical intermediate or the health-care food composition for the treatment of rheumatoid arthritis.

Extract of the present invention is:

The percentage by weight that contains following compounds in the Cortex Fraxini mandshuricae extract is respectively: fraxinol glycosides 50%-95%, fraxin 2%-15%, different scopolin 0.1%-1%, isofraxidin-β-D-Glucose glycosides 0.1%-1%.

Fraxinol glycosides, molecular formula are C ₁₇H ₂₀O ₁₀, structural formula is

Fraxin, molecular formula are C ₁₆H ₁₈O ₁₀, structural formula is

Different scopolin, molecular formula are C ₁₆H ₁₈O ₉, structural formula is

Isofraxidin-β-D-Glucose glycosides, molecular formula are C ₁₇H ₂₀O ₁₀, structural formula is

Extraction process of the present invention is:

Water Qu Liuye (or skin) is raw material, adds 90%-98% ethanol to extract, 75 ℃ of-85 ℃ of heating and refluxing extraction 3 times, and each 1.5 hours, merge extractive liquid,, decompression recycling ethanol gets extractum A.Extractum A is disperseed with distilled water, with isopyknic petroleum ether extraction 3 times, remove oils and fats and the little compound of chlorophyll isopolarity, add the remaining petroleum ether of heat extraction, upper Diaion HP-20 type macroporous resin column, first be eluted to the sugar-free reaction with distilled water, use subsequently the ethanol elution of 90%-98%, decompression recycling ethanol gets extractum B.Extractum B separates with 200-300 purpose silica gel, first use ethyl acetate-methanol-water (Capacity Ratio 8:2:0.5) to remove phenylethanoid glycoside, then use chloroform-methanol-water (Capacity Ratio 8:2:1 lower floor) eluting coumarin glycoside constituents, evaporate to dryness organic solvent, the solid that obtains are exactly the Cortex Fraxini mandshuricae extract.

the invention has the beneficial effects as follows: can use in the medicine for the treatment of rheumatoid arthritis, compare with chemical drugss such as hormones, its toxicity is low, safe and reliable, and Cortex Fraxini mandshuricae blade aboundresources, can turn waste into wealth, mention technique simple, the Cortex Fraxini mandshuricae extract can be for the preparation of pharmaceutical composition together with pharmaceutically acceptable excipient or adjuvant, compositions all can adopt the conventional method of galenic pharmacy to be prepared into various dosage forms, as tablet, pill, capsule, granule, tincture, gastrointestinal administration dosage form and the injections such as oral liquid, the gastrointestinal tract external administration dosage forms such as external preparation.

The specific embodiment

Embodiment 1:

The preparation of Cortex Fraxini mandshuricae extract

Take Cortex Fraxini mandshuricae fresh leaves 10kg, with rubbing, add 90% ethanol, 80 ℃ of heating and refluxing extraction 3 times, each 1.5 hours, merge extractive liquid,, decompression recycling ethanol gets extractum A.Extractum is disperseed with 2L distilled water (30 ℃), with isopyknic petroleum ether extraction 3 times, remove oils and fats and the little compound of chlorophyll isopolarity, add the remaining petroleum ether of heat extraction, upper Diaion HP-20 type macroporous resin column, first be eluted to the sugar-free reaction with distilled water, use subsequently 95% ethanol elution, decompression recycling ethanol gets extractum B.Extractum B separates with 200-300 purpose silica gel, first use ethyl acetate-methanol-water (Capacity Ratio 8:2:0.5) to remove phenylethanoid glycoside, then use chloroform-methanol-water (Capacity Ratio 8:2:1 lower floor) eluting coumarin glycoside constituents, evaporate to dryness organic solvent, the solid that obtains are exactly the Cortex Fraxini mandshuricae extract.

Prescription:

The Cortex Fraxini mandshuricae extract	50g
		Sodium carboxymethyl cellulose	10g
Food starch	233g
		Magnesium stearate	2g
Polyvinylpyrrolidone	5g
		Tablet	1000

Preparation method: medicine and adjuvant are crossed respectively 80 mesh sieves, take recipe quantity Cortex Fraxini mandshuricae extract and food starch, 75% alcoholic solution soft material processed of the polyvinylpyrrolidone with 5%, cross 20 mesh sieves, drying, granulate, add sodium carboxymethyl cellulose, magnesium stearate, direct compression, and get final product.

Effect experiment research

The Wistar rat, 6-8 week, 30, male and female half and half, body weight (160 ± 15) g is divided into 3 groups at random, 10 every group, is respectively negative control group, positive controls, administration group.Positive controls and administration group rat are brought out rheumatoid arthritis and occur at left hind foot pad subcutaneous injection complete Freund's adjuvant (CFA, Sigma).The administration group begins to give Cortex Fraxini mandshuricae extract, gastric infusion once a day at CFA immediately to inflammation; Positive controls and negative control group give the normal saline of same dose, gavage simultaneously.

Give CFA and cause two groups of scorching rats all to begin to occur the sufficient pawl of injection in 2-3 days in injection CFA red, swollen, hot, the acutely inflamed performance such as dysfunction, lasting after 4-7 days symptom alleviate gradually.Approximately begin to occur the whole body delayed hypersensitivity take polyarthritis as feature after 10 ~ 14d, pathological changes is involved the sufficient pawl of not injecting CFA, shows as different red, swollen, the heat of local joint degree and dysfunction.Along with the course of disease extends, polyarthritis can occur repeatedly.

The arthroncus degree of rheumatic arthritis is marked with the 0-4 level, 0 minute: without arthritis; 1 minute: little toe joint mild swelling; 2 minutes: little toe joint and the sole of the foot were red and swollen; 3 minutes: the sufficient pawl swelling that ankle joint is following; 4 minutes: comprise the whole arthroncuss of ankle joint.Scoring just is being defined as rheumatoid arthritis more than 1 minute.Arthritis mark (AS) is that (the mark summation is calculated AS respectively at 14d, 21d, 28d after modeling between 0-16, use the SPSS13.0 statistical analysis, the results are shown in Table 1 for the summation of each arthropathy mark of every Mus.

Table 1 administration group and positive group AS contrast (± s)

Group	n	14d	21d	28d
					Positive controls	10	7.00±1.054	10.20±0.789	12.30±0.823
The administration group	10	6.20±1.033	*5.80±1.229	*5.10±1.370

* the administration group is compared with positive group, P＜0.05

After modeling 28d, separately draw medicine group and positive group rats with bilateral ankle joint, through fixing, decalcification, conventional gradient dehydration, waxdip, embedding, section, tissues observed section pathological change under light microscopic after H E dyeing.The hyperplasia of the group of causing a disease lymphocyte of adjurant arthritis rat, synovial tissue's cell infiltration, synovial membrane thickens, synovial membrane and cartilage join domain synovial cell proliferation, the cartilage injury, bone trabecula attenuates, bone erosion appears in subchondral bone and trabecular bone, destroys seriously, does not even observe complete trabecular bone structure.Administration group rat synovium of joint has a small amount of lymphocytic infiltration without obvious hypertrophy in synovial membrane.

Toxic and side effects research

In acute toxicity test, when giving mice daily dose 22.4g/kg, 10 mices do not occur dead and obvious intoxicating phenomenon, are 112 times of dosage 200mg/kg in above-mentioned pharmacodynamics test, so the Cortex Fraxini mandshuricae extract is safe and reliable.

Claims (2)

1. Cortex Fraxini mandshuricae extract for the treatment of rheumatoid arthritis, its extract is: the percentage by weight that contains following compounds in the Cortex Fraxini mandshuricae extract is respectively: fraxinol glycosides 50%-95%, fraxin 2%-15%, different scopolin 0.1%-1%, isofraxidin-β-D-Glucose glycosides 0.1%-1%;

Fraxinol glycosides, molecular formula are C ₁₇H ₂₀O ₁₀, structural formula is

Fraxin, molecular formula are C ₁₆H ₁₈O ₁₀, structural formula is

Different scopolin, molecular formula are C ₁₆H ₁₈O ₉, structural formula is

Isofraxidin-β-D-Glucose glycosides, molecular formula are C ₁₇H ₂₀O ₁₀, structural formula is

。

2. a kind of extraction process for the treatment of the Cortex Fraxini mandshuricae extract of rheumatoid arthritis as claimed in claim 1, its extraction process is: water Qu Liuye or skin are raw material, add 90%-98% ethanol to extract, 75 ℃ of-85 ℃ of heating and refluxing extraction 3 times, each 1.5 hours, merge extractive liquid,, decompression recycling ethanol gets extractum A; Extractum A is disperseed with distilled water, with isopyknic petroleum ether extraction 3 times, remove oils and fats and the little compound of chlorophyll isopolarity, add the remaining petroleum ether of heat extraction, upper Diaion HP-20 type macroporous resin column, first be eluted to the sugar-free reaction with distilled water, use subsequently the ethanol elution of 90%-98%, decompression recycling ethanol gets extractum B; Extractum B separates with 200-300 purpose silica gel, first remove phenylethanoid glycoside with Capacity Ratio 8:2:0.5 ethyl acetate-methanol-water, then use the chloroform-methanol of Capacity Ratio 8:2:1-water elution coumarin glycoside constituents, evaporate to dryness organic solvent, the solid that obtains are exactly the Cortex Fraxini mandshuricae extract.