CN105497003A - Application of icaritin to preparation of medicine for preventing or treating pulmonary fibrosis - Google Patents
Application of icaritin to preparation of medicine for preventing or treating pulmonary fibrosis Download PDFInfo
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- CN105497003A CN105497003A CN201410505292.4A CN201410505292A CN105497003A CN 105497003 A CN105497003 A CN 105497003A CN 201410505292 A CN201410505292 A CN 201410505292A CN 105497003 A CN105497003 A CN 105497003A
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- pulmonary fibrosis
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Abstract
The invention relates to application of icaritin to the preparation of medicine for preventing or treating pulmonary fibrosis and belongs to the field of medicine. The icaritin is traditional Chinese medicine monomer extracted from traditional Chinese medicine epimedium. Animal experiments show that the icaritin has evident preventing and treating effects on the pulmonary fibrosis. The icaritin is definite in curative effect on the pulmonary fibrosis, low in side effect and promising in medical application prospect.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of medical usage of epimedium aglucone, be specifically related to the medical usage of epimedium aglucone in preparation prevention or treatment pulmonary fibrosis medicine.
Background technology
Pulmonary fibrosis is the final pathological change of multiple interstitial lung disease, it is characterized in that long-term Diffuse alveolar is scorching, fibroblast hyper-proliferative, then occur that extrtacellular matrix deposition is too much, and replace normal lung tissue gradually, finally cause pulmonary dysfunction, patient may be dead because of respiratory failure.Pulmonary fibrosis can be divided into reason bright (as lonizing radiation, medicine, pneumosilicosis etc.) and the large class of reason not bright (as idiopathic pulmonary fibrosis) two substantially.Research thinks that the many factors such as pathogenic microorganism, dust, medicine, chemicals all can the generation of inducing lung fibrosis, but its detailed mechanism it be unclear that.Pulmonary fibrosis can betide any age, and global incidence is 7-10/10 ten thousand, and patient's mean survival time is 3-4, and with advancing age, sickness rate increases gradually and the mean survival time shortens gradually.As can be seen here, the health of the pulmonary fibrosis serious harm mankind and existence, the research and development of anti-fibrosis drug seem very important.
The medicine of current pulmonary fibrosis resistant mainly contains: 1) glucocorticoid, is the main selection of current clinical treatment, but this kind of Drug side reaction is large, has a strong impact on body's immunity, increases the probability of secondary infection; 2) interferon gamma (IFN-γ), untoward reaction is more, easily bring out tolerance; 3) cytotoxic drug (azathioprine, cyclophosphamide etc.), medicine poor selectivity, untoward reaction are many; 4) antioxidant (N-acetylcystein etc.), curative effect is not ideal enough; 5) other drug, colchicine, pyrrole coffee ketone etc.Given this, the medicine of efficient, the safe treatment pulmonary fibrosis of development of new is necessary.
Herba Epimedii is the dry aerial parts of Berberidaceae plant Herba Epimedii, Epimedium sagittatum, Epimedium acuminatium, Epimedium wushanense or Herba Epimedii.Herba Epimedii contains multiple flavones ingredient, as icariin, icariside, epimedium aglucone (Icaritin, ICT) etc.The traditional Chinese medical science thinks its acrid in the mouth, sweet, warm in nature, returns liver, kidney channel, cures mainly function: kidney-replenishing, bone and muscle strengthening, wind-damp dispelling.Epimedium aglucone belongs to flavonoid drugs, is present in epimedium herb on a small quantity, and its chemical structural formula is as follows:
Epimedium aglucone can be separated and obtain (Sun Pengyue, Xu Ying, Wen Ye etc., the chemical composition of Herba Epimedii, Chinese Plants The Chemicals, 1998,8 (2): 122-125 from the cylinder metabolism-ure of epimedium herb or icariin; Liu strong determined person, Wang Yi, Wu Lijun etc., the Enterobacter cloaca metabolism research I. intestinal bacterium of icariin is to the metabolic conversion of icariin, 2000,31 (11): 834-837), or by icariin through enzymolysis be separated and obtain (leaf swell, Liu Jian, Lou Yijia, the preparation of two derivatives from icariin and investigation and estrogen-like effects thereof, journal of Zhejiang university, 2005,34 (2): 131-136).
Have bibliographical information epimedium aglucone to have effect (Zhang Xiangnan that anti-A β peptide causes rat primary cultured nerve cell apoptosis, Wang Huanhuan, Wang Zhiqiang etc., epimedium aglucone anti-A β peptide causes the effect of rat primary cultured nerve cell apoptosis, journal of Zhejiang university, 2007,36 (3): 224-226).Chinese patent CN101836976A discloses the effect that epimedium aglucone has Antineoplastic angiogenesis.Chinese patent CN101428015A discloses the effect that epimedium aglucone has treating endotoxemia.Chinese patent CN101284000A discloses epimedium aglucone and has the effect preventing and treating obesity or fatty liver.Chinese patent CN1869204A discloses the purposes of epimedium aglucone in induced dry-cell vitro directed differentiation.Chinese patent CN1194701C discloses epimedium aglucone or demethyl epimedium aglucone to be had and is preparing the application in estrogenic agents.
But the research up to now, had no about epimedium aglucone pulmonary fibrosis resistant biological activity or clinical practice aspect.
Summary of the invention
The invention provides the medicine of a kind of new prevention or treatment pulmonary fibrosis, this medicine take epimedium aglucone as active constituents of medicine.Epimedium aglucone is a kind of Chinese medicine monomer extracted from Herba Epimedii, prior art shows that it has multiple therapeutic activity, therefore the present invention relates to a kind of new medical usage of epimedium aglucone, i.e. the purposes of epimedium aglucone in preparation prevention or treatment pulmonary fibrosis medicine.
In medical usage described above, epimedium aglucone can be prepared into suitable pharmaceutical dosage form oral administration or drug administration by injection, and its applicable object can be people or other Homoiotherms.When applicable object is behaved, the consumption of epimedium aglucone is preferably 0.001mg/kgd ~ 50mg/kgd, more preferably 0.01mg/kgd ~ 10mg/kgd.The administration time of medicine of the present invention's prevention or treatment pulmonary fibrosis and administration number of times are needed to the concrete diagnostic result according to the state of an illness and determine, and this is within the technical scope of those skilled in the art's grasp.Such as, will be applied on the person to the therapeutic scheme of mice prevention or treatment pulmonary fibrosis, medicine used can be converted by the effective dose of this medicine to mice to the effective dose of people, and this is apparent for the person of ordinary skill of the art.
In medical usage described above, epimedium aglucone can be prepared into suitable pharmaceutical preparation to facilitate medication according to the animal state of an illness and agents area, as epimedium aglucone can be developed to the use that oral formulations, sublingual administration preparation or ejection preparation facilitate patient, wherein said oral formulations can be tablet, capsule or microemulsion formulation, is preferably tablet; Described sublingual administration preparation is containing epimedium aglucone and is suitable for the pharmaceutical preparation of sublingual administration, is preferably its Sublingual tablet; Described ejection preparation can be its injection, injection microemulsion etc., is preferably injection.When epimedium aglucone is prepared into injection, medicine acceptable carrier can be water for injection, sodium chloride, sodium citrate, citric acid, glycerol, ethanol, propylene glycol etc.Epimedium aglucone injection described above can also add suitable additives according to the character of medicine, as osmotic pressure regulator, pH value regulator, solubilizing agent, the agent for the treatment of oxygen, antibacterial, emulsifying agent, suspending agent etc., wherein said solubilizing agent is any one or two kinds in PEG400, tween 80.
The preparation method of said medicine preparation all can adopt those skilled in the art to prepare this kind of dosage form routine use preparation method and obtain.In said medicine preparation, the content containing epimedium aglucone in each preparation unit is 0.001mg ~ 50mg.
Compared with prior art, advantage of the present invention is:
1, epimedium aglucone of the present invention has the effect of significant prevention or treatment pulmonary fibrosis.The embodiment of the present invention 10 shows the survival rate that epimedium aglucone of the present invention can significantly improve pulmonary fibrosis mice, improve the Lung Exponent of the index and spleen index of pulmonary fibrosis mice and thymus index, reduction pulmonary fibrosis mice, alleviate the pulmonary fibrosis degree of pulmonary fibrosis mice, pulmonary fibrosis tool is had significant therapeutic effect.
2, epimedium aglucone of the present invention is from Chinese medicine Herba Epimedii, extract the natural Chinese medicine monomer obtained, it is low to human body toxic and side effects, drug safety and the compliance of patient can be significantly improved, and then significantly improve therapeutic effect and the quality of life of pulmonary fibrosis patients.
Detailed description of the invention
In order to make those skilled in the art fully understand the present invention, further illustrate the present invention below by way of specific embodiment, but those skilled in the art should know, the embodiment of the present invention does not also limit the present invention in any way.
Embodiment 1 epimedium aglucone injection
Preparation technology: by the propylene glycol of recipe quantity and ethanol mix homogeneously, add epimedium aglucone, stirring and dissolving, adds 0.9% sodium chloride solution of recipe quantity, stirs, add 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 2 epimedium aglucone injection
Preparation technology: the PEG-400 to recipe quantity adds epimedium aglucone, stirring and dissolving, adds 0.9% sodium chloride solution to 10L, stirs, add 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 3 epimedium aglucone injection
Preparation technology: by the ethanol of recipe quantity and tween 80 mix homogeneously, add epimedium aglucone, stirring and dissolving, add water for injection to 10L, stir, add 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 4 epimedium aglucone injection
Epimedium aglucone 0.01g
Ethanol 3.3L
Water for injection adds to 10L
Preparation technology: the ethanol of recipe quantity is added epimedium aglucone, stirring and dissolving, adds water for injection to 10L, stirs, and adds 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
The preparation of embodiment 5 tablet
Preparation technology: by epimedium aglucone and microcrystalline cellulose excipients, carboxymethyl starch sodium mix homogeneously, add appropriate starch slurry soft material, then crosses 16 mesh sieves and granulates.Wet granular is 60 DEG C of dryings, and dry granule crosses 20 mesh sieve granulate, sifts out the fine powder in dry granular, mixes with magnesium stearate, and then mixes with dry granule, tabletting, and every agreement that contracts a film or TV play to an actor or actress 200mg, to obtain final product.
Embodiment 6 epimedium aglucone Sublingual tablet
Preparation technology: said components is dried, pulverize and sieve and mix direct compression after pretreatment and obtain.
Embodiment 7 epimedium aglucone Sublingual tablet
Preparation technology: principal agent and each adjunct ingredient are dried, pulverizes and sieves pretreatment, principal agent and sugar, lactose, sodium carboxymethyl cellulose are mixed, using pure water as binding agent, the material of mixing is prepared soft material, cross 20 mesh sieves granulate and at 60 DEG C the dry granule of dry preparation, magnesium stearate is joined above-mentioned dry granule always to mix, tabletting and get final product.
Embodiment 8 microemulsion concentrate
Preparation technology: take recipe quantity medium chain length fatty acid triglyceride, Polyoxyethylene castor oil EL-40,1,2-propylene glycol, dehydrated alcohol, stir after mixing, then add epimedium aglucone to dissolve, also can ultrasonic Treatment with accelerate dissolution, must concentrated solution be clarified, be epimedium aglucone microemulsion concentrate.Above-mentioned microemulsion concentrate can dilute further for injection or oral.
Embodiment 9 microemulsion concentrate
Preparation technology: stir after taking recipe quantity PEG-2-stearate, tween 20,1-hexanol, PEG3350 mixing, then add epimedium aglucone to dissolve, also can ultrasonic Treatment with accelerate dissolution, obtain clarification concentrated solution, be epimedium aglucone microemulsion concentrate.Above-mentioned microemulsion concentrate can need to carry out dilution further for patient's drug administration by injection or oral administration according to medication.
Embodiment 10 epimedium aglucone is to the Effect study of mouse pulmonary fibrosis
1. animal grouping and administration
Healthy ICR mice, SPF level, male, 105, body weight (20 ± 2) g, mice is divided into 7 groups at random by body weight, often organizes 15, be respectively dosage injection group, epimedium aglucone high dose injection group, epimedium aglucone gavage group, Dexamethasone group in Normal group, model control group, epimedium aglucone low dosage injection group, epimedium aglucone.Lumbar injection chloral hydrate 350mg/kg anesthetized mice, Normal group tracheal instillation normal saline, all the other 6 groups of tracheal instillation bleomycin (5mg/kg), make medicinal liquid be uniformly distributed in lung mice vertical rotary 2min immediately after instillation, put back in cage and normally raise.
Epimedium aglucone and dexamethasone 0.5% sodium carboxymethyl cellulose suspendible, from after modeling the 2nd day, successive administration, once a day, normal group and model group such as to give at 0.5% sodium carboxymethyl cellulose of capacity.
Each group gives following medicine respectively:
Normal group: isopyknic sodium carboxymethyl cellulose, lumbar injection
Model control group: isopyknic sodium carboxymethyl cellulose, lumbar injection
Epimedium aglucone low dosage injection group: 1mg/kg epimedium aglucone, lumbar injection
Dosage injection group in epimedium aglucone: 3mg/kg epimedium aglucone, lumbar injection
Epimedium aglucone high dose injection group: 9mg/kg epimedium aglucone, lumbar injection
Epimedium aglucone gavage group: 15mg/kg epimedium aglucone, gastric infusion
Dexamethasone group: 5mg/kg dexamethasone sodium phosphate injection, lumbar injection
2. experimental technique and date processing
Every day measures Mouse Weight, record mouse diing time.After modeling the 30th day, lumbar injection chloral hydrate 350mg/kg anesthetized mice, ventral aorta sacrificed by exsanguination, got mouse spleen, thymus and lung, weighs.Get each group of mice inferior lobe of left lung, be placed in 4% formaldehyde and fix, all the other lung tissues are placed in-70 DEG C of freezen protective.
The statistics of 2.1 mouse survival rates
The survival rate of the 30th day after statistics mice modeling.
The calculating of 2.2 mouse spleens, thymus, Lung Exponent
Calculate spleen, thymus, the Lung Exponent of each group mice as follows.
The calculating of 2.3 mouse pulmonary fibrosis degree
After lung tissue fixes 1 week, conventional dehydration, embedding, section, with reference to (SzapielSV such as Szapiel, ElsonNA, FulmerJD.Bleomycin-inducedinterstitialpulmonarydiseasein thenude, athymicmouse [J] .AmRevRespirDis, 1979, the degree of method evaluation pulmonary fibrosis 120:893.), and ranked data are converted into measurement data.Without alveolitis or pulmonary fibrosis (-, 1 point); Slight alveolitis or pulmonary fibrosis (+, 2 points); Moderate alveolitis or pulmonary fibrosis (++, 3 points); Severe alveolitis or pulmonary fibrosis (+++, 4 points).
2.4 data statisticss and analysis
Data with
represent, adopt SPSS15.0 software to carry out variance analysis.
3. result and discussion
3.1 epimedium aglucones are on the impact of pulmonary fibrosis mice survival rate
Table 1 epimedium aglucone causes the impact of pulmonary fibrosis mice survival rate to bleomycin
Table 1 result shows: after modeling the 30th day, and model group mouse survival rate is 53.3%; Dexamethasone group survival rate is close with model group; Epimedium aglucone basic, normal, high dosage injection group mouse survival rate is 60.0%, 93.3%, 73.3%; Epimedium aglucone gavage group mouse survival rate is 66.7%.Show that epimedium aglucone can significantly improve the survival rate of pulmonary fibrosis mice.
The impact of 3.2 excessive icariin units on pulmonary fibrosis mice spleen, thymus, Lung Exponent
Table 2 epimedium aglucone causes the impact of pulmonary fibrosis mice spleen, thymus, Lung Exponent to bleomycin
Compared with Normal group,
$p<0.05,
$$p<0.01;
Compared with model control group,
#p<0.05,
##p<0.01;
Table 2 result shows, epimedium aglucone can improve index and spleen index and the thymus index of pulmonary fibrosis mice, reduces the Lung Exponent of pulmonary fibrosis mice.
3.3 epimedium aglucones are on the impact of pulmonary fibrosis mice various pulmonary lesions
Table 3 epimedium aglucone causes the impact of pulmonary fibrosis mice pulmonary fibrosis degree to bleomycin
Compared with Normal group,
$p<0.05,
$$p<0.01;
Compared with model control group,
#p<0.05,
##p<0.01;
As shown in table 3, after modeling the 30th day, model group lung fibrosis degree was very serious, and epimedium aglucone is respectively organized and can significantly be lowered pulmonary fibrosis degree with Dexamethasone group, wherein in epimedium aglucone dosage injection group to reduce the effect of pulmonary fibrosis degree best.
In sum, epimedium aglucone has the effect preventing and/or treating pulmonary fibrosis disease.
Claims (7)
1. the purposes of epimedium aglucone in preparation prevention or treatment pulmonary fibrosis medicine.
2. purposes as claimed in claim 1, is characterized in that people's dosage of described epimedium aglucone is 0.001mg/kgd ~ 50mg/kgd.
3. purposes as claimed in claim 2, is characterized in that people's dosage of described epimedium aglucone is 0.01mg/kgd ~ 10mg/kgd.
4. purposes as claimed in claim 1, is characterized in that described epimedium aglucone is oral formulations, sublingual administration preparation or ejection preparation.
5. purposes as claimed in claim 4, is characterized in that described oral formulations is its tablet, capsule or microemulsion formulation.
6. purposes as claimed in claim 4, is characterized in that described ejection preparation is for its injection or injection microemulsion.
7. purposes as claimed in claim 4, is characterized in that the content containing epimedium aglucone in each preparation unit is 0.001mg ~ 50mg.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109394776A (en) * | 2018-11-26 | 2019-03-01 | 河南中医药大学 | A kind of traditional Chinese medicinal components side that treating diffusivity pulmonary interstitial fibrosis and its application |
Citations (1)
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| CN101284002A (en) * | 2008-02-29 | 2008-10-15 | 中国人民解放军第二军医大学 | Medicine for preventing and curing liver injury |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284002A (en) * | 2008-02-29 | 2008-10-15 | 中国人民解放军第二军医大学 | Medicine for preventing and curing liver injury |
Non-Patent Citations (3)
| Title |
|---|
| JING LI,等: "Icaritin induces cell death in activated hepatic stellate cells through mitochondrial activated apoptosis and ameliorates the development of liver fibrosis in rats", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| 吴红媛，等: ""中药对组织器官纤维化防治机制研究"", 《中国实验方剂学杂志》 * |
| 徐长青: ""淫羊藿苷对卵蛋白和内毒素诱导炎症反应的影响及机制研究"", 《中国博士学位论文全文数据库》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109394776A (en) * | 2018-11-26 | 2019-03-01 | 河南中医药大学 | A kind of traditional Chinese medicinal components side that treating diffusivity pulmonary interstitial fibrosis and its application |
| CN109394776B (en) * | 2018-11-26 | 2020-08-25 | 河南中医药大学 | Traditional Chinese medicine component formula for treating diffuse interstitial pulmonary fibrosis and application thereof |
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