CN107569486A - Menglusitena treats the new application of thrombopenia - Google Patents

Abstract

The invention discloses a kind of application of Menglusitena in the diseases related medicine of the clinical common megakaryocytopoiesis decrease of platelet for the treatment of is prepared, substantial amounts of medical expense is saved for patient, while toxic side effect is slight, and also patient tolerability is good.

Description

Menglusitena treats the new application of thrombopenia

Technical field

The invention belongs to biomedicine field, is related to a kind of new application of Menglusitena treatment thrombopenia.

Background technology

The relevant disease of decrease of platelet

Decrease of platelet relevant disease clinic is common, easily causes the bleeding of the important organ such as cerebral hemorrhage and causes death, clinic danger Evil is big.Medical expense is expensive, and ineffective, needs economic, effective and slight toxic side effect treatment method badly.

Thrombocytopenic disease, it is the common disease of hematology and oncology, each clinical training is quite a few sees for other, often Aggravation can be caused or influence operation, severe patient even jeopardizes patient vitals.Malignant tumor patient is after radiation and chemotherapy Blood platelet substantially reduces, and its reason is clearer and more definite, often obtains paying much attention to and sufficiently treats.And for some non-malignant tumors For thrombocytopenic Disease caused by radiation and chemotherapy factor, sometimes with more potential dangerous.

In addition to the clear and definite chemicotherapy Platelet of the cause of disease reduces patient, the thrombocytopenic Disease cause of disease is substantially It is divided into four classes, essential thrombocythemia reduces and accounts for 30%；Secondary cases decrease of platelet accounts for 57%；Acatalepsia accounts for 12.0%；False blood is small Plate reduces and accounts for 1%.Wherein Secondary cases decrease of platelet is divided into non-blood systemic disease factor and disease in the blood system factor.Non- blood Liquid systemic disease factor mainly has：Hypersplenia, hepatitis, chemicotherapy correlation decrease of platelet, rheumatic disease etc..Blood Liquid systemic disease factor mainly has：Immune thrombocytopenia（ITP）, acute leukemia（AL）, alpastic anemia （AA）, myelodysplastic syndrome（MDS）, megaloblastic anemia（MA）, non-Hodgkin's lymphoma（NHL）, iron-deficient it is poor Blood（IDA）Deng.

Thrombocytopenic disease, be a kind of clinically common disease in the blood system, using decrease of platelet and bleeding as Main clinical manifestation, reduced with thrombocytopoiesis in marrow, autoantibody produces, network blood platelet removes three kinds of morbidity machines System is caused a disease.Current platelet reduce property disease primary treatment regimen have platelet transfusion, TPO, interleukin-11, Chinese medicine etc., but all do not have good economy, it is impossible to thrombocytopenic disease is fast and effectively treated, to patient and family Category brings white elephant, wherein the form of therapy of primary refractory thrombocytopenic disease is then more severe.For The treatment of primary refractory thrombocytopenic Disease mainly suppresses autoantibody generation, reduction blood platelet is broken Bad, stimulating platelet generation, key agents have glucocorticoid, intravenous immunoglobulin, Rituximab, TPO receptor agonisms Agent etc..However, these therapies do not make intractable ITP obtain persistently reaction, and drug side-effect influences life in patients.

Although thrombocytopenic disease has a variety of causes to cause, reduced including thrombocytopoiesis, destruction increases. But it is main factor that thrombocytopoiesis, which is reduced, and is to cause blood small because TPO signal path can not be activated effectively The main factor that plate generation is reduced.The medicine of activation TPO/MPL paths mainly has at present：Recombined human thrombopoietin, Chinese mugwort Bent ripple pa, Luo meter Si Ting, interleukin-11 etc..But these medicines can not effectively solve thrombocytopenic disease, and medicine The big influence life in patients of side effect, while family of the expensive medical expense also to patient brings white elephant.These The medicine treatment expenses for medicine of one month is at least in ten thousand yuans of 3-4.

In this context, the inventors discovered that, activation TPO/MPL signal paths can effectively facilitate thrombocytopoiesis, control It is diseases related to treat decrease of platelet, including immunity decrease of platelet, alpastic anemia blood platelet related to chemicotherapy Reduce.

On Menglusitena medicine

Menglusitena is a kind of non-hormone anti-inflammatory agent, suitable for being grown up and the prevention of more than 1 years old childhood asthma and controlling for a long time Treatment and the treatment of allergic rhinitis, are a kind of LTRAs, mainly by airway smooth muscle and other cell tables The antagonism of colourless triene acceptor, suppress the cause asthma for the cysteinyl leukotriene that mast cell and eosinophil discharge and cause Inflammation effect, produce slight bronchodilatation and mitigate allergen, motion and so₂Bronchial spasm of induction etc. acts on, and has A certain degree of antiinflammatory action, toxic side effect is low, cheap, and patient's medical expense of one month is about at 100 yuans Left and right.

The content of the invention

The technical problems to be solved by the invention are to provide Menglusitena and are preparing the clinical common megacaryocyte for the treatment of The application in the diseases related medicine of decrease of platelet is generated, substantial amounts of medical expense, while toxic side effect are saved for patient Slightly, and patient tolerability is good.

Technical scheme provided by the invention is：Menglusitena is small in the clinical common megakaryocytopoiesis blood of preparation treatment Plate reduces the application in diseases related medicine.

The clinical common megakaryocytopoiesis decrease of platelet of Menglusitena treatment is diseases related, including immunity blood platelet Reduction property purpura, alpastic anemia, radiotherapy Platelet reduces and chemotherapy-related decrease of platelet.

Dosage

1mg-100mg, 1-3/ day.It is various with various formulations, such as tablet, capsule, suspension, oral or injection and Neulized inhalation Mode method of administration.

Above-mentioned application, it is preferable that Menglusitena dosage is 10mg.

The invention has the advantages that：The inventors discovered that Menglusitena, which has, promotes thrombopoietic effect. Clinical principium applies 42 patients, and effective percentage is more than 60%.It is following small in treatment blood if invention can be obtained to authorize Can be that patient saves substantial amounts of medical expense in terms of plate relevant disease, while toxic side effect is slight, patient tolerability is good.Make me State's decrease of platelet relevant disease is in the leading level in the world.

Brief description of the drawings

Fig. 1 Menglusitenas promote the RT-PCR results of Dami cell lines expression c-MPL genes,

Dami cell lines, Mon Menglusitenas, cont control groups.

Fig. 2 Menglusitenas promote the differentiation of MEG cell lines Dami cells, and left figure is not use Medicine Dami cell lines（Blank control group）, right figure is to have added the Dami cells after Menglusitena culture.

There is polyploid performance in Fig. 3 Menglusitenas induction Dami cell lines.

Fig. 4 Menglusitenas treat the effect of 1 refractory/recurrence immunologic thrombocytopenic purpura（Model case 1）.

Fig. 5 Menglusitenas treat the effect of 1 refractory/recurrence immunologic thrombocytopenic purpura（Model case 2）.

Fig. 6 Menglusitenas treat the effect of 1 refractory/recurrence alpastic anemia（Model case 3）.

Embodiment

Below by embodiment detailed description come the present invention is furture elucidated, but be not to the present invention limit System, is only illustrated.

Embodiment one：Menglusitena promotes megakaryocytic series Dami cell platelets to generate plain acceptor c-MPL gene tables Reach and the research of Dami cell differentiations

1. Menglusitena promotes the experimental study of Dami cell line c-MPL gene expressions

The PCR primer design of 1.1 c-MPL genes

5′-TCCCCCCAGTATCATCAAGGC -3′

3′-GGCAGGTCCACAGTCACAGGG -5′;

The length of PCR primer is 441bp.

β-actin :

5′-GGCATGGGTCAGAAGGATTCC -3′

3′-GGCCAGAGGCGTACAGGGATA -5′

Forward primer and reverse primer are typically all from 5 ' to 3 ' directions, and β-actin PCR primer length is 304bp.

Take the logarithm growth period cell megakaryocytic leukemia Dami cell lines, with 1 × 10⁸/ L density is inoculated in 24 Orifice plate, experimental group add final concentration of 10 μm of ol/L Menglusitena in nutrient solution, and control group is not added with.After cultivating 72h, one Part cell extracts total serum IgE with TriZol, takes 1 μ g total serum IgE to be dissolved in the pure water of no RNase, is synthesized with reverse transcriptase CDNA, 10 μ L cDNA RT-PCR Laemmli buffer system Laemmlis are taken, the PCR that 25 circulations are carried out according to above-mentioned primer is expanded.Test above It is repeated 3 times.

Result

Fig. 1 is referred to, RT-PCR results show, Menglusitena has the function that to promote Dami cell lines expression c-MPL genes.

Menglusitena promotes the experimental study of Dami cell lines differentiation

Dami cell lines are in Menglusitena（10µmol/L）After culture 72 hours, cell volume becomes big, and occurs adherent Phenomenon.This fully shows adhesive attraction of the normal megakaryocytes to culture dish, and volume becomes big, and the tumour by 2 times of bodies Cell, break up to the mature cell of polyploid.Prompting, Menglusitena have the function that to promote megakaryocyte differentiation, referred to Fig. 2.

As can be seen from Fig. 3, Menglusitena makes Dami cell lines that polyploid change, intracellular visible multiple nucleus occur Exist simultaneously, the phenomenon for having prompted Menglusitena to promote Dami cells polyploid differentiation occur.

Embodiment two：Menglusitena treats the hematoblastic Preliminary Clinical of refractory/recurrent

So far, the present inventor treats refractory/recurrent thrombopenia 42 in clinical practice Menglusitena, Including immunologic thrombocytopenic purpura, aplastic anaemia, radiotherapy Platelet reduces related to chemotherapy Property decrease of platelet.42 patients are by the invalid patient of traditional 1 line treatment, wherein 28 patients are effective, using department spy Blood platelet is increased beyond one times after sodium, and efficient 61%, data statistics is see table 1 below

The Menglusitena of table 1 treats the concept clinical curative effect of refractory/recurrent decrease of platelet

Disease name	Number of cases	Effectively	It is efficient（%）
				Immunologic thrombocytopenic purpura	21	17	81
Aplastic anaemia	5	3	60
				Radiotherapy Platelet is reduced	7	5	71
Chemotherapy-related decrease of platelet	9	3	33
				It is total	42	28	61.25

It is typical case below, including refractory/recurrent immunologic thrombocytopenic purpura 2 and 1 heavy regeneration barrier Impenetrability Anemic patients.It is specific as follows：

Model case 1：Menglusitena treats refractory/recurrent immunologic thrombocytopenic purpura

Patient, a * *, man, 27 years old, main cause immunologic thrombocytopenic purpura was admitted to hospital on 2 1st, 2017.Blood is small when being admitted to hospital Plate 1 × 10⁹/ L, through human immunoglobulin(HIg), after dexamethasone and TPO and rituximab treatment January, blood is small Plate is still 1 × 10⁹/L -2×10⁹/ L is fluctuated.In the case, start on March 16th, 2017 on probation oral once a night 10mg Menglusitena, as a result blood platelet is on March 30th, 2017, that is, adds Menglusitena after 2 weeks i.e. up to completely normal, Refer to Fig. 4.

Model case 2：Menglusitena treats refractory/recurrent immunologic thrombocytopenic purpura

Patient, Liu * *, man, 90 years old.Because haemophilia is gone to a doctor for 4 hours after occurring double lower limb bleeding suddenly and brush teeth.In 2016 November 3 was admitted to hospital.Enter platelet of having a blood test after section can't detect, checked through bone marrow aspiration etc., be diagnosed as immune thrombocytopenic Purpura.Because of advanced age, the medical history such as the past diabetes and prostate cancer, refuse standard dose hormone therapy.Give human immunoglobulin(HIg) defeated Note after 1 week blood platelet rise to 55 × 10⁹/ L, 2 days blood platelets are again lowered to 2 × 10 after drug withdrawal⁹/ L, and with gum and skin Bleeding.Blood platelet rises to 15 after adding the Menglusitena 1 week with oral 10mg once a night, continuously takes January so far, blood platelet Maintain 100 × 10⁹/ more than L, not again repeatedly, refer to Fig. 5.

Model case 3：Menglusitena treats refractory/recurrent alpastic anemia

Patient, a * *, female, 32 years old.Because more than 20 years of aplastic anaemia are in March, 2015 outpatient clinic.Mouth once Take the treatments such as cyclosporine, androgen, injection antihuman globulin.But blood platelet in 1-2 or so, needs weekly infusion 1-3 mono- all the time Position Single-donor platelets.Because HLA distribution type is difficult, HSCT can not be carried out.After adjustment therapeutic scheme 6 months, blood Platelet is still without progress, weekly there is still a need for 1-2 per platelet of infusion.On original treatment basis since in October, 2015 On, Menglusitena 10mg is added, 1 time/evening is so far.Blood platelet can be stablized between 50-80 at present, refer to Fig. 6.

Claims (7)

1. application of the Menglusitena in the diseases related medicine for the treatment of megakaryocytopoiesis decrease of platelet is prepared.

2. according to the application described in claim 1, it is characterised in that：Described megakaryocytopoiesis decrease of platelet correlation disease Disease is diseases related for clinical common megakaryocytopoiesis decrease of platelet.

3. according to the application described in claim 1, it is characterised in that：Described megakaryocytopoiesis decrease of platelet correlation disease Disease is immunologic thrombocytopenic purpura, and alpastic anemia, radiotherapy Platelet reduces or chemotherapy-related blood Platelet is reduced.

4. according to the application described in claim 1, it is characterised in that：Menglusitena dosage is 1mg-100mg, 1-3 times/day.

5. according to the application described in claim 3, it is characterised in that：Menglusitena dosage is 10mg.

6. according to the application described in any one of claim 1 to 5, it is characterised in that：The formulation of Menglusitena is suitable to oral, note Penetrate or Neulized inhalation.

7. according to the application described in claim 6, it is characterised in that：Described formulation is tablet, capsule, Alevaire or suspension.