CN104546823B - Epimedium aglucone treats or prevents the purposes in decrease of platelet disease drug in preparation - Google Patents
Epimedium aglucone treats or prevents the purposes in decrease of platelet disease drug in preparation Download PDFInfo
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Abstract
The present invention relates to a kind of novel medical uses of epimedium aglucone, and in particular to epimedium aglucone treats or prevents the purposes in decrease of platelet disease drug in preparation, belongs to field of medicaments.In order to overcome thrombopenia therapeutic agent therapeutic effect in the prior art cannot persistently, be discontinued technical deficiency easy to recur and big side effect, the present invention provides a kind of therapeutic agent containing epimedium aglucone, the drug can significantly increase the platelet levels of patient when for thrombopenia especially immune thrombocytopenia, embody significant therapeutic effect.The drug also has significant therapeutic effect in the decrease of platelet that treatment bone marrow suppression causes.When epimedium aglucone is treated for thrombopenia, has the advantages that curative for effect, medical expense is low, toxic side effect is small, be highly suitable for promoting and applying in clinic.
Description
Technical field
The present invention relates to a kind of novel medical uses of epimedium aglucone, and in particular to epimedium aglucone is in preparation treatment or in advance
Purposes in anti-decrease of platelet disease drug, belongs to field of medicaments.
Background technique
Thrombopenia is decrease of platelet in peripheral blood (100,000/μ l of <) and leads to mucocutaneous and visceral hemorrhage
Disease, be mainly shown as that white hair skin petechia and ecchymosis, mucosal bleeding, nosebleed epistaxis and bleeding gums, mucous membrane of mouth and tongue go out
Existing purple bleeding blister etc., is clinical common a kind of disease with the characteristics of coagulation disorders, bleeding, and severe one can cause big bleeding,
Threat to life, clinic account for about the 30% of hemorrhagic disease.
The reason of decrease of platelet can be divided into: (1) thrombocytopoiesis is reduced or invalid dead: including heredity and acquired
Two kinds, acquired thrombocytopoiesis reduction is since certain factors such as drug, malignant tumour, infection, ionising radiation equivalent damage are made
Hemocytoblast influences that multiple hematopoietic cell systems can be influenced caused by it is proliferated in marrow, is often accompanied by different degrees of anaemia, white
Leukopenia, bone marrow megakaryocyte significantly reduce；(2) platelet destruction is excessive: including congenital and two kinds acquired.It is acquired
Platelet destruction excessively includes immunity and non-immunity.Immunity platelet destruction excessively common are essential thrombocytopenia and subtract
Few property purpura and drug decrease of platelet.Non-immunity decrease of platelet destroy excessively include infection, disseminated intravascular coagulation,
Thrombotic thrombocytopenic purpura etc.；(3) blood platelet is detained excessively in spleen: being most commonly in hypersplenia.
The pathogenesis of thrombopenia includes: that sexual factor 1) is immunized: clinical visible severe liver disease, lupus erythematosus, spy
The case where immunity diseases such as hair property thrombocytopenic purpura cause decrease of platelet, antibody destroys blood platelet；2) infectious
Factor: causing the common factors of thrombopenia, bacterium, virus infection can coup injury hematopoietic cell, it is raw to reduce blood platelet
Long, the acute attack stages such as alpastic anemia, acute leukemia often with severe infections, have hemorrhagic tendency, as having the stasis of blood on skin
The performances such as point, erythema or the unknown nosebleed of reason；3) drug sexual factor: because some drugs cause blood platelet meter in peripheral blood
Hemorrhagic disease caused by number is reduced；4) platelet function abnormality: such as thrombasthenia, Giant platelet syndrome.
Thrombopenia is mainly immunologic thrombocytopenic purpura (immunethrombocytopenic in clinic
Purpura, ITP) and thrombotic thrombocytopenic purpura (thromboticthrombocytopenic purpura, TTP)
Two class diseases are relatively common.Wherein, ITP is the most common reason of clinical findings decrease of platelet.For a long time, ITP is considered
It is hemorrhagic disease caused by a kind of decrease of platelet that reason is unknown, thus referred to as primary or essential thrombocytopenia are reduced
Property purpura (idiopathic thrombocytopenicpurpura).There are identify itself for discovery ITP patient's body later
The combination of the autoantibody of platelet antigen, autoantibody and platelet antigen cause platelet life span shorten, destroy increase and
Platelet counts are reduced, and illustrate that this disease is a kind of hemorrhagic disease relevant to immune response.
In clinic, immunologic thrombocytopenic purpura (ITP) is a kind of relatively conventional hemorrhagic disease, estimates people
The disease incidence of ITP is 1/10000 in group, can be occurred in any age level.Normal children is mostly acute, adult mostly slow
Property type, mostly occur in children and youth, clinical manifestation is that skin petechia and ecchymosis, skin and mucosa bleeding, patient with severe symptoms companion occurs
Arthralgia or abdominal pain, hematochezia, haematemesis, collapse etc., serious person can develop as purpura nephritis.Idiopathic thrombocytopenic is purple
Purplish or white patches on the skin is a kind of immunity syndrome, is common hemorrhagic disease, and feature is that there are antiplatelet antibodies in blood circulation, makes blood
Platelet destroys excessively, causes purpura；And megacaryocyte is normal in marrow or increases, primitivization.
Up to the present, western medical treatment thrombocytopenic purpura is first choice with cortex hormone of aadrenaline, although hormone energy
Increased platelets counts, but after hormone decrement or stopping, blood platelet can decline again；Commonly using hormone, very to human body side effect
Greatly, such as central obesity, hypertension, diabetes disease can also be caused while treatment.Other treatment method is such as transfused blood
The methods of platelet, splenectomy treatment, have increase infection rate, cause active peptic ulcer, bleeding, immune function decline,
The features such as making exacerbation of symptoms and not lasting curative effect instead after hyperglycemia etc. and drug withdrawal；It is normal using immunosuppressor, splenectomy etc.
Therapy is advised, so that many patients is formed Hormone Withdrawal because of the contraindication of hormone and side effect and subtracts syndrome and cannot eradicate；And it is immunized
The toxic side effect of inhibitor is larger, easy to recur after drug withdrawal, easily leads to bone marrow suppression and the danger of induced tumor and cannot answer extensively
With.In recent years, large dosage of third pellet impact, the new treatments such as plasma exchange continuously emerge, but still lack the remedy measures of essence.
Herba Epimedii is Berberidaceae plant Herba Epimedii (Epimedium brevicornum Maxim.), Epimedium sagittatum
(Epimedium sagittatumMaxim.), E. Pubescens (Epimedium pubescens Maxim.) or Korea are excessive
The drying cauline leaf of the sheep leaves of pulse plants (Epimedium koreanum Nakai).Clinically it is mainly used for kidney-yang deficiency, impotence frequent micturition is infertile；
Rheumatic arthralgia, extremity numbness muscular constricture, muscles and bones impotence are walked with difficulty；Kidney-yang deficiency breathes with cough and loses heart.Icariin can increase heart and brain blood
Pipe blood flow promotes hematopoiesis function, immune function and bone metabolism, has tonifying kidney and strengthening yang, anti-aging, antitumor and other effects.Excessive sheep
Leaves of pulse plants aglycon (icaritin, IT) is one of Berberidaceae barrenwort Herba Epimedii polyhydroxy flavonoids monomer component.Medicine
Reason research shows that, IT function of resisting osteoporosis is strong compared with other flavonoid glycoside compounds in Herba Epimedii, in vitro have promote skeletonization
Cell activity inhibits the effect of osteoclast activity.In recent years as the icariin of important activity ingredient in Herba Epimedii and excessive
Sheep leaves of pulse plants aglycon is increasingly by the concern of medical personal.It is being made as patent application CN101637467A discloses epimedium aglucone
Application in standby treatment medicine for treating osteoporosis.Patent US6399579 discloses epimedium aglucone in terms of the treatment of sexual dysfunction
Purposes.Qiang Ningxia (is published in " Jilin Chinese medicine at " therapy of combing traditional Chinese and Western medicine chronic idiopathic thrombocytopenic purpura 30 "
Medicine " the 7th phase in 2010) in strengthening spleen, tonifying kidney Chinese medicine (ginseng, Radix Astragali, Radix Angelicae Sinensis, Fructus Corni, excessive sheep are added on the basis of western medical treatment
The treatment chronic idiopathic thrombocytopenic purpura such as the leaves of pulse plants, psoralea corylifolia achieves preferable therapeutic effect, but the drug contain it is more
Kind active constituent, the mechanism of action are complicated, it is necessary to carry out finer mechanism study and drug efficacy study.Zhao Yong etc. is in " Herba Epimedii
Glucoside collaboration induces IL-2, the researchs of 3,6 effects " it is thin using relying in (being published in " China Immunology Journal " the 1st phase in 1996)
Born of the same parents' strain method has detected the effect that icariine collaboration induces IL-2, IL-3 and IL-6 respectively, the results showed that icariine can cooperate with
PHA induce tonsillotome mononuclearcell generate IL-2,3,6, be in dose-dependence, prompt icariine be a kind of effective life
Object reaction control agent.
Summary of the invention
In order to overcome in the prior art thrombopenia therapeutic agent therapeutic effect cannot persistently, be discontinued it is easy to recur and
The big technical deficiency of side effect, the present invention provide a kind of thrombopenia therapeutic agent, and the drug is based on epimedium aglucone
Active constituent is wanted, is used to have curative for effect, Small side effects, the spy not rebounded after drug withdrawal when the treatment of thrombopenia
Point is very suitable to the clinical use of levels in patients with thrombocytopenia.
Epimedium aglucone is that the effective therapeutic component obtained is extracted from Herba Epimedii, proves epimedium aglucone on evidence
With extensive pharmacological activity, therefore the medical usage new the present invention relates to one kind of epimedium aglucone, i.e. epimedium aglucone exist
Preparation treats or prevents the purposes in decrease of platelet disease drug.
In present invention medicinal usage described above, the thrombopenia is immune thrombocytopenia.This
Inventive embodiments 13 confirm that epimedium aglucone can embody positive therapeutic effect to chronic ITP rat model, rise
It is better than positive control drug icariin in terms of high blood platelet.Its high, middle dose group has extremely significant raising rat platelet effect
(P < 0.01).As it can be seen that Chinese medicine composition of the present invention can be applied to the pharmaceutical preparation of preparation treatment thrombopenia,
It is particularly applicable to the pharmaceutical preparation of preparation treatment immune thrombocytopenia.
In present invention medicinal usage described above, the thrombopenia is preferably that the blood that is caused of bone marrow suppression is small
Plate reduces disease.The wherein bone marrow suppression that the bone marrow suppression is caused by chemicals.The confirmation of the embodiment of the present invention 15, excessive sheep
Leaves of pulse plants aglycon treatment group and icariin group all have positive therapeutic effect to the reduction of mouse caused by cyclophosphamide mouse platelets,
The platelet counts that caused by cyclophosphamide mouse platelets reduce model can be increased, wherein each treatment group of epimedium aglucone is rising
The platelet counts of high cyclophosphamide induced mice animal model are better than icariin group, and epimedium aglucone is increasing ring
Embody dose dependent in terms of the platelet counts of phosphamide induced mice animal model, epimedium aglucone high group and
Group is compared with icariin group with the difference of conspicuousness in epimedium aglucone.
Application of the epimedium aglucone disclosed by the invention in terms of preparing as treatment decrease of platelet disease drug, usually
Taken in the form of pharmaceutical composition, orally available or non-oral administration, or with pharmaceutically acceptable carrier, excipient
And compound (such as tablet, sustained release preparation, capsule, the injection, solution) safety of other additives formation is oral or non-
Oral administration.The people being wherein administered orally is 0.1mg/kg/d-100mg/kg/d with dosage；Non-oral administration is preferably injected
Administration, wherein the people of epimedium aglucone is preferably 0.01mg/kg-10mg/kg with dosage.When administered orally, composition can
It is configured to tablet, granule or capsule.To prepare, lactose is can be used in combination of oral medication or starch does carrier, gelatin, carboxylic
Sodium carboxymethylcellulose pyce, methylcellulose, polyvinylpyrrolidone etc. are suitable bonding agents or at granular agent.It is optional as disintegrating agent
With starch or microcrystalline cellulose, often with talcum powder, santocedl, tristerin, calcium stearate or magnesium etc. are as suitable
Antiadhesives and lubricant.For example, tablet can be prepared by compacting wet granular.Active constituent and carrier and selectivity with
Portion disintegration additive composition mixture, the aqueous solution of the mixture and adhesive, alcohol or aqueous alcohol solution are suitable
Equipment in granulated, other disintegrating agents, lubricant and antiplastering aid is then added by this mixture tabletting in dry particle.
Series compound of the invention can be administered in the form of injection, although dosage according to treatment object, administration mode, symptom and it is other because
Element and change.The dosage for the epimedium aglucone compound actually taken should determine by doctor according to related situation, these
Situation includes the physical condition of patient, individual reaction of the administration route, age, weight, patient of the person of choosing to drug, patient
Severity of symptom etc..The ejection preparation is one of injection, freeze drying powder injection, infusion preparation, the injection
Pharmaceutic adjuvant in preparation is one of mannitol, glucose, sorbierite, PEG, ethyl alcohol, physiological saline or a variety of, is preferably contained
There is the ejection preparation of PEG.
Be applicable in the pharmaceutical preparation containing epimedium aglucone of medicinal usage described above, the pharmaceutical preparation it is each
Amount in preparation unit containing epimedium aglucone is 0.1-500mg.
The medical usage of epimedium aglucone of the present invention has following technical advantage compared with prior art:
1) significant therapeutic effect is all had when the thrombopenia that epimedium aglucone causes for many factors.This hair
When bright embodiment 13 proves that epimedium aglucone is especially used for immune thrombocytopenia, increasing, chronic ITP model is big
It is better than positive control drug icariin in terms of mouse blood platelet.Its high, middle dose group has extremely significant raising rat platelet effect
(P < 0.01).Embodiment 14 confirms, also imitates with positive treatment in terms for the treatment of mouse active immunization decrease of platelet
Fruit.
2) epimedium aglucone also has positive therapeutic effect for the thrombopenia that bone marrow suppression causes, this prompt
Its detrimental effect that can be used in conjunction with other chemicals to reduce chemicals to body.The embodiment of the present invention 15 confirms, excessive
Yang Huo aglycon treatment group and icariin group, which reduce mouse caused by cyclophosphamide mouse platelets, all has positive treatment work
With the platelet counts that caused by cyclophosphamide mouse platelets reduce model, wherein each treatment group of epimedium aglucone can be increased
Increase caused by cyclophosphamide mouse platelets reduce model platelet counts be better than icariin group, high group of epimedium aglucone
There is compared with icariin group the difference of conspicuousness with group in epimedium aglucone.
3) epimedium aglucone is the extracted effective active composition from traditional Chinese medicine Herba Epimedii, is used for thrombopenia
It is not only curative for effect when treatment, it is suitable for drug combination, and its poisonous side effect of medicine is extremely low, can greatly increase the medication of patient
Compliance, to guarantee the therapeutic effect of drug.And epimedium aglucone is at present there are many preparation method, preparation process is simple, at
This is cheap, can substantially reduce the medical expense of levels in patients with thrombocytopenia.
Specific embodiment
The present invention is further described below by way of specific embodiment, but those skilled in the art should be able to know, this hair
Bright specific embodiment is not limit the invention in any way.
(1) example of formulations part
1 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 10mg
Propylene glycol 3ml
Ethyl alcohol 0.5ml
0.9% sodium chloride solution adds to 10ml
____________
Preparation process:
The propylene glycol of recipe quantity and ethyl alcohol are uniformly mixed, epimedium aglucone is added, recipe quantity is added in stirring and dissolving
0.9% sodium chloride solution, stirs evenly, be added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
2 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 10mg
PEG-400 2ml
0.9% sodium chloride solution adds to 10ml
__________
Preparation process: epimedium aglucone is added in the PEG-400 of recipe quantity, 0.9% sodium chloride solution is added in stirring and dissolving
To 10ml, stir evenly, be added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
3 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 50mg
Ethyl alcohol 3.5ml
Tween-80 1.5g
Water for injection adds to 10ml
Preparation process: the ethyl alcohol of recipe quantity and Tween-80 are uniformly mixed, and epimedium aglucone is added, and stirring and dissolving is added
0.9% sodium chloride solution is stirred evenly to 10ml, is added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
4 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 30mg
Ethyl alcohol 2ml
Tween-80 1.5g
Water for injection adds to 10ml
Preparation process: the ethyl alcohol of recipe quantity and Tween-80 are uniformly mixed, and epimedium aglucone is added, and stirring and dissolving is added
0.9% sodium chloride solution is stirred evenly to 10ml, is added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
5 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 5mg
Ethyl alcohol 2ml
Tween-80 1.5g
Water for injection adds to 10ml
Preparation process: the ethyl alcohol of recipe quantity and Tween-80 are uniformly mixed, and epimedium aglucone is added, and stirring and dissolving is added
0.9% sodium chloride solution is stirred evenly to 10ml, is added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
6 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 20mg
Ethyl alcohol 3.3ml
Water for injection adds to 10ml
Preparation process: epimedium aglucone is added in the ethyl alcohol of recipe quantity, stirring and dissolving is added water for injection to 10ml, stirs
Mix uniformly, be added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
7 epimedium aglucone injection of embodiment
Prescription:
Epimedium aglucone 10mg
Ethyl alcohol 3.3ml
Water for injection adds to 10ml
Preparation process: epimedium aglucone is added in the ethyl alcohol of recipe quantity, stirring and dissolving is added water for injection to 10ml, stirs
Mix uniformly, be added 0.5% needle-use activated carbon, stirring, take off charcoal to get.
8 epimedium aglucone tablet of embodiment
Prescription:
Preparation process: the epimedium aglucone, starch, dextrin for weighing recipe quantity are uniformly mixed.Separately suitable 50% ethyl alcohol is added
Enter in mixed-powder, is uniformly mixed, wet grain, 60 DEG C or so dryings is made by 18 mesh nylon mesh in softwood processed, and dry granular moisture is answered
Control is below 1.5%.20 mesh sieves, then with magnesium stearate mix, tabletting to get.
9 epimedium aglucone capsule of embodiment
Prescription:
Epimedium aglucone 10g
Microcrystalline cellulose 300g
Superfine silica gel powder 12g
Preparation process: epimedium aglucone, microcrystalline cellulose, superfine silica gel powder crushing are sieved with 100 mesh sieve into mixing, directly filling glue
Capsule to obtain the final product.
10 epimedium aglucone granule of embodiment
Prescription:
Preparation process: epimedium aglucone, starch, dextrin, the cane sugar powder for weighing recipe quantity are uniformly mixed.It separately will be suitable
80% ethyl alcohol is incorporated in mixed-powder, is uniformly mixed, softwood processed, is made wet grain by 18 mesh nylon mesh, 60 DEG C or so dryings,
20 mesh sieves, packing to get.
11 epimedium aglucone sustained-release tablet of embodiment
Prescription:
Preparation process: the epimedium aglucone of recipe quantity, lactose and sustained release agent hypromellose are uniformly mixed and are added
Polyvinyl pyrrolidone granulation, dry at 40 DEG C -80 DEG C, the profit of recipe quantity is added in whole dry particl in dry particl
Lubrication prescription superfine silica gel powder mixes, special-shaped stamping.
(2) test examples part
Embodiment 12: influence of the epimedium aglucone to normal mouse bleeding time and clotting time
12.1 experimental animals and test medicine:
Kunming mouse, half male and half female, 20 ± 2.0g of weight；Wistar rat, 200 ± 20g of weight, half male and half female.It is real
Animal is tested to be provided by Shandong new era medicine company new drug pharmacology center.
Test medicine: epimedium aglucone: the self-control of southern Shandong pharmacy group new drug pharmacology center, purity are 99.5% or more.Excessive sheep
Leaves of pulse plants glycosides: using patent application CN101812100A embodiment, icariin is prepared in 2 preparation process, similarly hereinafter.
12.2. experimental group and administration
Kunming mouse 100 are taken, 5 groups, respectively blank control group (physiological saline group), icariin group are randomly divided into
(positive controls), epimedium aglucone high dose group, epimedium aglucone middle dose group and epimedium aglucone low dose group.Each component
It is not administered respectively by following administration modes.
Blank control group: isometric physiological saline is given in subcutaneous injection
Icariin group: the icariin of 2mg/kg is given in injection；
High group of epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 10mg/kg；
Group in epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 5mg/kg；
Low group of epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 1mg/kg；
The measurement in 12.3 bleeding times and clotting time
The measurement in bleeding time: setting physiological saline group (blank control group), icariin group (positive controls), administration
Group (high, medium and low), chooses mouse 50, and weighing is randomly divided into 5 groups, every group 10.Successive administration 3d, in 1h after the last administration
After take filter paper to be rolled into filtration paper cylinder similar with mouse body diameter, it is closed at one end, allow mouse to pierce；Then mouse tail is cut with scissors
Point about 3mm, manual time-keeping is pressed since bleeding, dubs Mouse Tail-tip with filter paper every 15s, up to no bloodstain or does not see blood
It is the bleeding time between clocking, the results are shown in Table 1 until mark.
The measurement in clotting time: setting physiological saline group (blank control group), icariin group (positive controls), administration
Group (high, medium and low), chooses mouse 50, and weighing is randomly divided into 5 groups, every group 10.After 3d is administered, after last dose 1h,
Blood is taken with disposable 20 μ l heparin tube insertion mouse endocanthion ball rear vein beard, takes full 20 μ l blood.It fractures capillary one every 15s
Segment, checks for the appearance of blood clotting silk, and record the results are shown in Table 1 from blood sampling to the time (clotting time) for fiber protein yarn occur
It is shown.
The measurement result in table 1. bleeding time and clotting time
| Group | n | Dosage | Bleeding time | Clotting time |
| Blank control group | 10 | — | 5.11±0.62 | 5.68±0.72 |
| Icariin group | 10 | 2mg/kg | 4.03±0.45* | 4.28±0.61* |
| High group of epimedium aglucone | 10 | 10mg/kg | 1.86±0.24**△△ | 1.96±0.16**△△ |
| Group in epimedium aglucone | 10 | 5mg/kg | 2.51±0.35**△ | 3.04±0.31**△ |
| Low group of epimedium aglucone | 10 | 1mg/kg | 3.75±0.46* | 3.84±0.55* |
Note: compared with blank control group,*P < 0.05,**P < 0.01；Compared with icariin group,△P < 0.05,△△P <
0.01。
As can be seen from Table 1, when epimedium aglucone treatment group and icariin group can reduce the bleeding of normal mouse
Between and the clotting time, wherein each treatment group of epimedium aglucone reduce normal mouse bleeding time and clotting time in terms of be better than
Icariin group, epimedium aglucone embodies dose dependent in terms of reducing normal mouse bleeding time and clotting time, excessive
Group is compared with icariin group with the difference of conspicuousness in sheep leaves of pulse plants aglycon high group and epimedium aglucone.
Embodiment 13: influence of the epimedium aglucone to ITP platelet counts
The preparation of 13.1 models and grouping administration
It establishes chronic ITP model: choosing Wistar rat and made using injection rabbit-anti rat platelet serum (APS) method
Mould, the diluted APS of rats by intraperitoneal injection 1:4 (0.7ml/200g weight), continues 3 days, platelet counts can be made to significantly reduce.Choosing
Modeling success rat 50 is taken, weighing is randomly divided into 5 groups, respectively animal packet: blank control group, and icariin group is (positive
Control group), administration group (high, medium and low 3 dosage groups), every group 10.Each group gives following therapeutic agents respectively.
Blank control group: isometric physiological saline is given
Icariin group: the icariin of 2mg/kg is given in injection；
High group of epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 10mg/kg；
Group in epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 5mg/kg；
Low group of epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 1mg/kg；
13.2 each treatment group's rat platelets count
After last dose 1h, blood is taken with disposable 20 μ l heparin tube insertion mouse endocanthion ball rear vein beard, measures rat
Total number of blood platelet the results are shown in Table shown in 2.
The measurement result that 2. each group rat platelet of table counts
| Group | n | Dosage | Platelet count (× 109) |
| Blank control group | 10 | — | 423.6±52.4 |
| Icariin group | 10 | 2mg/kg | 571.8±60.6* |
| High group of epimedium aglucone | 10 | 10mg/kg | 819.96±61.8**△△ |
| Group in epimedium aglucone | 10 | 5mg/kg | 720.4±60.3**△ |
| Low group of epimedium aglucone | 10 | 1mg/kg | 680.84±50.5* |
Note: compared with blank control group,*P < 0.05,**P < 0.01；Compared with icariin group,△P < 0.05,△△P <
0.01。
As can be seen from Table 2, epimedium aglucone treatment group and icariin group can increase ITP rat platelet number
Amount, wherein each treatment group of epimedium aglucone is increasing ITP rat platelet quantity better than icariin group, and epimedium aglucone is rising
High ITP rat platelet quantity embodies dose dependent, group and icariin in epimedium aglucone high group and epimedium aglucone
Group is compared to the difference with conspicuousness.
To sum up, epimedium aglucone can embody positive therapeutic effect to chronic ITP rat model, slow reducing
Property the thrombin time of ITP rat model, prothrombin time and partial thromboplastin time in terms of and increased platelets counts side
Face is better than positive control drug icariin.Its high, middle dose group can significantly shorten the thrombin time of chronic ITP rat model
(TT), prothrombin time (PT) and partial thromboplastin time (APTT) (P < 0.05), and there is extremely significant raising rat serum
Platelet acts on (P < 0.01).As it can be seen that Chinese medicine composition of the present invention can be applied to the medicine of preparation treatment thrombopenia
Object preparation is particularly applicable to the pharmaceutical preparation of preparation treatment immune thrombocytopenia.
Influence of 14 epimedium aglucone of embodiment to mouse active immunization decrease of platelet
The preparation of 14.1 models and grouping administration
Balb/C mouse 72 are chosen, weighing is randomly divided into 5 treatment groups, respectively, normal group, blank control group is excessive
Sheep leaves of pulse plants glycosides group (positive controls), administration group (high, medium and low 3 dosage groups), every group 12.Except for the normal group, other treatment group
The blood platelet of SD rat is injected intraperitoneally in Balb/C mouse, once a week, continuously platelet counts can be made to significantly reduce three times.It makes
Mould starts second day afterwards, and following therapeutic agents are given respectively by each treatment group:
Normal group: giving isometric physiological saline
Blank control group: isometric physiological saline is given
Icariin group: the icariin of 20mg/kg is given in stomach-filling；
High group of epimedium aglucone: stomach-filling gives embodiment 8 epimedium aglucone tablet, dosage 100mg/kg；
Group in epimedium aglucone: stomach-filling gives embodiment 1 epimedium aglucone tablet, dosage 50mg/kg；
Low group of epimedium aglucone: stomach-filling gives embodiment 1 epimedium aglucone tablet, dosage 10mg/kg；
Each treatment group is administered once a day, normal to feed.After modeling three times, each treatment group continues administration one week.It anaesthetizes small
Mouse takes blood, detects platelet counts, investigates the influence of epimedium aglucone human peripheral blood platelet count (PLT).
14.2 experimental results
The measurement result of the influence of epimedium aglucone human peripheral blood platelet count (PLT) is as shown in table 3.
Influence of 3 epimedium aglucone of table to mouse active immunization decrease of platelet
#: compared with Normal group, p < 0.05；**: compared with blank control group, p < 0.01.
As can be seen from Table 3, epimedium aglucone treatment group and icariin group are to mouse active immunization decrease of platelet
Positive therapeutic effect is all had, active immunization decrease of platelet mouse mouse platelet counts can be increased, wherein Herba Epimedii
Each treatment group of aglycon is better than icariin group, excessive sheep in the platelet counts for increasing mouse active immunization animal model
Leaves of pulse plants aglycon embodies dose dependent, excessive sheep in terms of the platelet counts for increasing mouse active immunization animal model
Group is compared with icariin group with the difference of conspicuousness in leaves of pulse plants aglycon high group and epimedium aglucone.
Influence of 15 epimedium aglucone of embodiment to caused by cyclophosphamide mouse platelets reduction
The preparation of 15.1 models and grouping administration: choosing Balb/C mouse 72, and weighing is randomly divided into 6 treatment groups, point
It is not normal group, blank control group, icariin group (positive controls), administration group (high, medium and low 3 dosage groups), every group
12.50mg/kg cyclophosphamide is injected intraperitoneally in mouse daily, platelet counts can be made to significantly reduce within continuous one week.Modeling starts
The last week, following therapeutic agents were given respectively by each treatment group:
Normal group: giving isometric physiological saline
Blank control group: isometric physiological saline is given
Icariin group: the icariin of 2mg/kg is given in injection；
High group of epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 10mg/kg；
Group in epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 5mg/kg；
Low group of epimedium aglucone: subcutaneous injection 1 epimedium aglucone injection of embodiment, dosage 1mg/kg；
Each treatment group is administered once a day, normal to feed.After successive administration 3 weeks, anesthetized mice takes blood, detects blood platelet
Quantity investigates the influence of epimedium aglucone human peripheral blood platelet count (PLT).Measurement result is as shown in table 3.
Influence of 4 epimedium aglucone of table to caused by cyclophosphamide mouse platelets reduction
#: compared with Normal group, p < 0.05；**: compared with blank control group, p < 0.01.
As can be seen from Table 4, epimedium aglucone treatment group and icariin group are small to mouse caused by cyclophosphamide mouse blood
Plate reduction all has positive therapeutic effect, can increase the platelet count that caused by cyclophosphamide mouse platelets reduce model
Amount, wherein each treatment group of epimedium aglucone is better than in the platelet counts for increasing caused by cyclophosphamide mouse platelets reduction model
Icariin group, epimedium aglucone embody in terms of the platelet counts for increasing caused by cyclophosphamide mouse platelets reduction model
Dose dependent out, group is compared with icariin group with the difference of conspicuousness in epimedium aglucone high group and epimedium aglucone.
Claims (8)
1. epimedium aglucone treats or prevents the purposes in decrease of platelet disease drug in preparation, it is characterised in that the blood platelet
Reduce the thrombopenia that disease is caused by immune thrombocytopenia or bone marrow suppression.
2. the purposes as described in claim 1, it is characterised in that the immune thrombocytopenia is chronic idiopathic
Thrombocytopenic purpura.
3. purposes as described in claim 1, which is characterized in that the marrow that the bone marrow suppression is caused by chemicals
Inhibit.
4. the purposes as described in claim 1-3 is any, which is characterized in that Shi Renyong dosage is administered orally in epimedium aglucone
For 0.1mg/kg/d-100mg/kg/d.
5. purposes a method according to any one of claims 1-3, which is characterized in that epimedium aglucone drug administration by injection Shi Renyong dosage
For 0.01mg/kg-10mg/kg.
6. purposes a method according to any one of claims 1-3, which is characterized in that epimedium aglucone is oral preparation or injection.
7. the purposes as described in claim 6, which is characterized in that the oral preparation is tablet, granule or capsule.
8. purposes as claimed in claim 7, which is characterized in that the oral preparation of the epimedium aglucone or injection it is every
Amount in one preparation unit containing epimedium aglucone is 0.1-500mg.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310493718.4A CN104546823B (en) | 2013-10-21 | 2013-10-21 | Epimedium aglucone treats or prevents the purposes in decrease of platelet disease drug in preparation |
| ES14855388T ES2698620T3 (en) | 2013-10-21 | 2014-10-20 | Icaritine for use in the prevention or treatment of hematocytopenia |
| KR1020167013370A KR101891505B1 (en) | 2013-10-21 | 2014-10-20 | Use of anhydroicaritin in preparing medicine for preventing or treating decrease in blood cells |
| PCT/CN2014/088944 WO2015058664A1 (en) | 2013-10-21 | 2014-10-20 | Use of icariin in preparing medicine for preventing or treating decrease in blood cells |
| JP2016525940A JP6294476B2 (en) | 2013-10-21 | 2014-10-20 | Use of anhydroicaritin in the manufacture of a medicament for preventing or treating cytopenias |
| US15/030,671 US10555962B2 (en) | 2013-10-21 | 2014-10-20 | Use of icaritin in preparing medicament for preventing or treating hematocytopenia |
| EP14855388.6A EP3061452B1 (en) | 2013-10-21 | 2014-10-20 | Icaritin for use in preventing or treating hematocytopenia |
| HK15105403.3A HK1204917A1 (en) | 2013-10-21 | 2015-06-08 | Sublingually buccal formulation of arctigenin |
| US16/724,573 US10799521B2 (en) | 2013-10-21 | 2019-12-23 | Use of icaritin in preparing medicament for preventing or treating hematocytopenia |
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| CN201310493718.4A CN104546823B (en) | 2013-10-21 | 2013-10-21 | Epimedium aglucone treats or prevents the purposes in decrease of platelet disease drug in preparation |
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| CN104688722B (en) * | 2013-12-04 | 2019-10-01 | 鲁南制药集团股份有限公司 | Purposes of the epimedium aglucone in preparation prevention or treatment bone marrow suppression drug |
| CN105476957B (en) * | 2014-12-18 | 2021-04-20 | 北京珅奥基医药科技有限公司 | Acoradine injection and preparation method and application thereof |
| CN113368099B (en) * | 2020-03-10 | 2024-03-26 | 鲁南制药集团股份有限公司 | Application of icariin in preparation of medicines for preventing and treating diseases related to platelet dysfunction |
| EP4119139A4 (en) * | 2020-03-10 | 2024-03-20 | Lunan Pharmaceutical Group Corporation | Medical use of anyhdroicaritin |
| CN113368098B (en) * | 2020-03-10 | 2024-03-29 | 鲁南制药集团股份有限公司 | Application of icariin in preparation of medicine for preventing and treating hemophilia |
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|---|---|---|---|---|
| CN1460482A (en) * | 2003-06-08 | 2003-12-10 | 浙江大学 | Medicine composite containing icaritin and demethylicaritin and its application |
| CN101812100A (en) * | 2010-04-08 | 2010-08-25 | 苏州宝泽堂医药科技有限公司 | Method for preparing icariin |
| WO2012045282A1 (en) * | 2010-10-08 | 2012-04-12 | 鲁南制药集团股份有限公司 | Applications of arctigenin in formulating medicines for preventing or treating diseases related to red blood cell reduction |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460482A (en) * | 2003-06-08 | 2003-12-10 | 浙江大学 | Medicine composite containing icaritin and demethylicaritin and its application |
| CN101812100A (en) * | 2010-04-08 | 2010-08-25 | 苏州宝泽堂医药科技有限公司 | Method for preparing icariin |
| WO2012045282A1 (en) * | 2010-10-08 | 2012-04-12 | 鲁南制药集团股份有限公司 | Applications of arctigenin in formulating medicines for preventing or treating diseases related to red blood cell reduction |
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