CN110403946A - Treat the purposes of chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong - Google Patents
Treat the purposes of chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong Download PDFInfo
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- CN110403946A CN110403946A CN201810394493.XA CN201810394493A CN110403946A CN 110403946 A CN110403946 A CN 110403946A CN 201810394493 A CN201810394493 A CN 201810394493A CN 110403946 A CN110403946 A CN 110403946A
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- shandong
- buddhist nun
- pulmonary hypertension
- anoxic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the purposes for treating chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong, the experimental results showed that, treating anoxic group rat according to Shandong for Buddhist nun can be increased with substantially reduced right ventricular pressure, HE coloration result shows that treating anoxic group rat pulmonary artery media thickness thickened degree according to Shandong for Buddhist nun mitigates, and flesh parteriole number significantly reduces.According to Shandong potential treatment prospect can be provided for treatment chronic hypoxic pulmonary hypertension for Buddhist nun.
Description
Technical field
Chronic hypoxic is treated in preparation the invention belongs to replace the applied technical field of Buddhist nun according to Shandong, more particularly to according to Shandong for Buddhist nun
The purposes of pulmonary hypertension drug.
Background technique
Pulmonary hypertension is one kind with multifactor caused chronic complexity cardiopulmonary and vascular disease, and major pathologic features are
Pulmonary artery pressure increases, lung resistance blood vessel hyperplasia and structure remodeling.Patients with pulmonary hypertension medical opportunity is often partially late, such trouble
After diagnosing, often development is right heart function failure to person one in several years, or even dead.Patients with pulmonary hypertension prognosis is very poor, for a long time
Survival rate is low, and case fatality rate is high, has become the public health event for endangering human health at present.
Chronic hypoxic lung arterial hypertension is the 3rd seed type in European Society of Cardiology's parting, is chronic obstructive pulmonary
The respiratory diseases such as disease and interstitial lung disease develop into a key link of right heart failure, cor pulmonale, are
A kind of pathologic, physiologic syndrome because caused by oxygen drops in alveolar characterized by pulmonary vascular resistance raising, vascular remodeling.
The therapeutic scheme of chronic hypoxic pulmonary hypertension is presently mainly to treat potential pulmonary disease at present, oxygen therapy,
Diuretics, anticoagulant, lung's rehabilitation and vaccine inoculation etc..It is high that these therapeutic schemes can only alleviate chronic hypoxic pulmonary artery
The symptom for pressing patient, has delayed the progress of disease to a certain extent, has reduced admission rate again and the death rate, but cannot be from root
The process of pulmonary hypertension is reversed in sheet.And targeted drug treatment only small-scale research, and the exacerbation of some targeted drugs is slow
The symptom of property Patients with Hypoxic Pulmonary Hypertension.
Replacing Buddhist nun according to Shandong is a kind of efficient irreversible small molecule Bruton tyrosine kinase inhibitor, can inhibit B cell
Proliferation and induce cell apoptosis.Treatment lymphoma mantle cell (MCL) and chronic lymphatic have been ratified by FDA at present for Buddhist nun according to Shandong
The B cells such as chronic myeloid leukemia (CLL), small lymphocyte lymthoma, marginal zone lymphoma and Waldenstrom's macroglobulinemia are related
Property tumour.Administration mode in treatment B cell associated tumors be oral, it was demonstrated that according to Shandong for Buddhist nun some drugs with reliably
Systemic administration safety.
Summary of the invention
In order to solve the problems in the existing technology, the present invention provides one kind and treats Chronic hypoxia in preparation for Buddhist nun according to Shandong
Property pulmonary hypertension drug purposes, overcome in the treatment of chronic hypoxic pulmonary hypertension in the prior art at present suit the medicine to the illness branch
Hold the problems such as therapeutic scheme cannot reverse pulmonary hypertension process and uncertain targeted drug therapeutic effect.
The technical scheme is that treating the purposes of chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong.
A kind of to treat chronic hypoxic pulmonary hypertension drug, active constituent is to replace Buddhist nun according to Shandong, is added pharmaceutically acceptable
Auxiliary material various dosage forms are made according to a conventional method.
The invention has the benefit that in the present invention, when being used to treat chronic hypoxic pulmonary hypertension for Buddhist nun according to Shandong,
Administration is safe.
Have the effect of significantly inhibiting chronic hypoxic pulmonary hypertension for Buddhist nun according to Shandong.The experimental results showed that being replaced according to Shandong
Buddhist nun is treated anoxic group rat and can be increased with substantially reduced right ventricular pressure, and HE coloration result, which is shown, treats anoxic group rat according to Shandong for Buddhist nun
Pulmonary artery media thickness thickened degree mitigates, and flesh parteriole number significantly reduces.Replacing Buddhist nun according to Shandong can be treatment Chronic hypoxia
Property pulmonary hypertension potential treatment prospect is provided.
Detailed description of the invention
Fig. 1 is that the right ventricular pressure of each group rat in embodiment 1 compares figure；Wherein A is normal oxygen+physiological saline group, and B is anoxic
+ physiological saline group, C are that anoxic+according to Shandong replaces Buddhist nun's group, and ordinate identifies the right ventricular pressure of every group of rat；
Fig. 2 is the HE morphological observation figure of normal oxygen+saline rats in embodiment 1；
Fig. 3 is anoxic+saline rats HE morphological observation figure in embodiment 1；
Fig. 4 be embodiment 1 in anoxic+according to Shandong for Buddhist nun organize rat HE morphological observation figure；
Fig. 5 is that the pulmonary artery media thickness of each group rat in embodiment 1 compares figure；Wherein A is normal oxygen+physiological saline group, B
For anoxic+physiological saline group, C is that anoxic+according to Shandong replaces Buddhist nun's group；Ordinate identifies the pulmonary artery media thickness of every group of rat.
Specific embodiment
The present invention is described in more detail in the following with reference to the drawings and specific embodiments.
Buddhist nun (ibrutinib) is replaced according to Shandong used in following embodiment and experimental example, is purchased from SELLECK company.
Embodiment 1
Various dosage forms are made according to a conventional method according to the auxiliary material that pharmaceutical acceptable is added for Buddhist nun in Shandong, as the liquid of various specifications is infused
Penetrate agent, powder needle injection, emulsion for injection, tablet, pill, capsule, paste, creme, patch, liniment, pulvis, spray,
Implant, drops, suppository, ointment, confection etc..
The administration route that Buddhist nun is replaced according to Shandong includes various administration routes: oral administration, drug administration by injection, drug delivery implant are intracavitary to give
Medicine, sublingual administration, anum administration, cutaneous penetration, interior external application etc..
Experimental example 1
In order to prove technological means, purpose and the experiment effect of this experiment invention, below with reference to specific experiment example, into one
Step illustrates the present invention.
(1) experimental material
1. experimental animal
SD rat, male, 350 ± 10g are purchased from Beijing Vital River Experimental Animals Technology Co., Ltd..Experimental animal purchase
Molding bay is placed on after entering to adapt to 7 days.
Animal feeding condition: 25 ± 1 DEG C of constant temperature, constant humidity 55 ± 5% is kept for light and shade each 12 hours, and diet feeds water.
2. experimental drug and configuration method:
Buddhist nun (ibrutinib) is replaced according to Shandong, SELLECK company is purchased from, storage requirement: 4 DEG C, being kept in dark place.Precision is weighed
Buddhist nun 22.5mg is replaced according to Shandong, stirring saves after 2.5ml normal saline dilution is added to 25 μ l DMSO are completely dissolved in.
(2) experimental method
1. model construction and drug-treated
Animal is randomly divided into normal oxygen+physiological saline group, anoxic+according to Shandong for Buddhist nun's group, anoxic+physiological saline group, every group 4
Only.Physiological saline is perfused according to 50mg/kg daily in normal oxygen+physiological saline group, anoxic+physiological saline group；Anoxic+according to Shandong replace Buddhist nun's group
It is perfused daily according to 50mg/kg through stomach and replaces Buddhist nun according to Shandong.All experimental rats, which are both placed in hypoxia culture box, raises, diet
Feed water.
Anoxic+physiological saline group, anoxic+be placed in organic glass anoxic case according to Shandong for Buddhist nun's group, oxygen concentration is 10% left
It is right；Normal oxygen+physiological saline group is placed in identical anoxic case, and oxygen concentration is normal oxygen.It periodically is passed through nitrogen toward anoxic case, to keep
Anoxic case oxygen concentration is constant.Daily exposure air is primary and the time is identical, is adjusted within every 3 days according to weight and replaces Buddhist nun or physiology according to Shandong
Salt water dosage.
2. haemodynamics detection and HE dyeing
After anoxic 28 days, after every animal anaesthetizes satisfaction with 20% urethane, with Powerlab biomedical information acquisition and place
Reason system carries out haemodynamics detection, and lung tissue is left and taken after detection and does pathological section and HE dyeing.
(3) experimental result:
1, to the influence of right ventricular pressure (Right ventricular systolic pressure, RVSP)
Normal oxygen+physiological saline group right ventricular pressure is 28.55 ± 3.85mmHg, the right heart after anoxic+physiological saline group anoxic 4 weeks
Room is increased to 47.58 ± 10.90mmHg, and the two is more statistically significant (P < 0.05).
Under anoxia condition, according to Shandong for Buddhist nun's prophylactic treatment can slow down pulmonary arterial pressure raising (25.03 ± 5.75mmHg, with
Anoxic+physiological saline group is more statistically significant (P < 0.05).Fig. 1 is seen, it can be seen that A group (normal oxygen+physiological saline group)
Right ventricular pressure be 28mmHg or so, the right ventricular pressure of B group (anoxic+physiological saline group) is 47mmHg or so, C group (anoxic+according to
Replace Buddhist nun's group in Shandong) right ventricular pressure be 25mmHg or so.It will be apparent that, Buddhist nun is replaced to test group effect according to Shandong bright by above-mentioned data
It is aobvious, the raising for the right ventricular pressure that can obviously inhibit chronic hypoxia to induce.It * is P < 0.05.
2, HE coloration result
Film is normal in normal oxygen+physiological saline group pulmonary artery HE dyeing prompt pulmonary artery, in anoxic+physiological saline group pulmonary artery
Film obviously thickens, and flesh parteriole number increased significantly, anoxic+according to Shandong for Buddhist nun organize pulmonary artery thicken unobvious, flesh parteriole
Number significantly reduces.See Fig. 2-5, it can be seen that the normal oxygen of Fig. 2+physiological saline group pulmonary artery media thickness is normal, lumen size
Normally.Fig. 3 anoxic+physiological saline group pulmonary artery media thickness obviously thickens, and lumen becomes smaller, and flesh parteriole number obviously increases
It is more.Fig. 4 anoxic+organize pulmonary artery media thickness according to Shandong for Buddhist nun thickens unobvious, and lumen size is substantially normal, flesh parteriole number
It reduces.The pulmonary artery media thickness of Fig. 5 A group (normal oxygen+physiological saline group) is 11% or so, B group (anoxic+physiological saline group)
Pulmonary artery media thickness is that the pulmonary artery media thickness of 29.5% or so, C group (anoxic+according to Shandong for Buddhist nun's group) is 19.5% or so.
It will be apparent that, replace Buddhist nun's experimental group effect obvious according to Shandong, the pathological lung that can obviously inhibit chronic hypoxia to induce by above-mentioned data
Vascular remodeling.It * is P < 0.05.
Although above in conjunction with attached drawing, invention has been described, and the invention is not limited to above-mentioned specific implementations
Mode, the above mentioned embodiment is only schematical, be not it is restrictive, those skilled in the art this
Under the enlightenment of invention, without breaking away from the scope protected by the purposes and claims of the present invention, many shapes can also be made
Formula, within these are all belonged to the scope of protection of the present invention.
Claims (2)
1. treating the purposes of chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong.
2. a kind of treat chronic hypoxic pulmonary hypertension drug, which is characterized in that its active constituent is to replace Buddhist nun according to Shandong, and medicine is added
It learns acceptable auxiliary material and various dosage forms is made according to a conventional method.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810394493.XA CN110403946A (en) | 2018-04-27 | 2018-04-27 | Treat the purposes of chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong |
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| CN201810394493.XA CN110403946A (en) | 2018-04-27 | 2018-04-27 | Treat the purposes of chronic hypoxic pulmonary hypertension drug in preparation for Buddhist nun according to Shandong |
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| CN110403946A true CN110403946A (en) | 2019-11-05 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024027750A1 (en) * | 2022-08-02 | 2024-02-08 | Beigene Switzerland Gmbh | Methods of treating pulmonary hypertension using btk inhibitors |
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2018
- 2018-04-27 CN CN201810394493.XA patent/CN110403946A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024027750A1 (en) * | 2022-08-02 | 2024-02-08 | Beigene Switzerland Gmbh | Methods of treating pulmonary hypertension using btk inhibitors |
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Application publication date: 20191105 |