CN110151738A - A kind of Jak2 inhibitor joint polygonin Alevaire and its preparation method and application - Google Patents
A kind of Jak2 inhibitor joint polygonin Alevaire and its preparation method and application Download PDFInfo
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- CN110151738A CN110151738A CN201910478315.XA CN201910478315A CN110151738A CN 110151738 A CN110151738 A CN 110151738A CN 201910478315 A CN201910478315 A CN 201910478315A CN 110151738 A CN110151738 A CN 110151738A
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- polygonin
- alevaire
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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Abstract
The invention belongs to drugs, medical preparation field, disclose a kind of Jak2 inhibitor joint polygonin Alevaire, and the Alevaire is made of Jak2 inhibitor, polygonin and hydrotropic solvent；Preparation method is also disclosed, includes the following steps (1), Jak2 inhibitor is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；(2), polygonin is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；(3), the two is mixed later in equal volume, makes its ultimate density up to 1mg/ml；Also disclose its application in preparation treatment chronic bronchitis drug.The present invention, it is significant to the therapeutic effect of chronic bronchitis, it is rapid-action, and be atomization preparation, convenient drug administration.
Description
Technical field
The present invention relates to drug, medical preparation field, specifically a kind of Jak2 inhibitor joint polygonin Alevaire and its
Preparation method and application.
Background technique
JAK inhibitor alternative inhibits JAK kinases, blocks JAK/STAT access, and JAK-STAT signal path is
The signal transduction pathway that one of discovered in recent years is stimulated by cell factor participates in the proliferation of cell, differentiation, apoptosis and immune
Many important biological processes such as adjusting.Clinically JAK inhibitor is mainly used for screening disease in the blood system, tumour, class wind
The therapeutic agents such as wet arthritis and psoriasis.
Polygonin is the extract of plant polygonum cuspidatum, can be used for antibechic, Adjust-blood lipid, reduces cholesterol, Hemorrhagic shock.Polygonin
Microcirculation can be improved, inhibit the release of lysosomal enzyme, it is anti-oxidant, prevent leucocyte in microcirculation viscous, reducing blood lipid, anti-grease matter mistake
The effects of oxidation, resisting pathogenic microbes, antibechic relievings asthma, antibacterial, antiviral, liver protection.Drug polygonum cuspidate glycoside injection liquid can treat cardiac muscle
The cardiovascular and cerebrovascular diseases such as ischemic, cerebral ischemia, shock.
Chronic bronchitis is common chronic nonspecific respiratory disease, and disease incidence is high, and the state of an illness is easily repeatedly, slowly
Property bronchitis is the chronic nonspecific inflammation of trachea-bronchial epithelial cell mucous membrane and surrounding tissue.Clinic is to cough, expectoration is main
Symptom, annual morbidity continue 3 months, and continuous 2 years or 2 years or more.Treatment chronic bronchitis clinical application at present is mostly antibacterial
Drug the disadvantage is that easily causing bacterial drug resistance, and causes adverse reaction.
Summary of the invention
The purpose of the present invention is to provide a kind of Jak2 inhibitor to combine polygonin Alevaire, is more accelerated using nebulizer formulation
Speed makes drug effect lesion, and to control state of an illness breaking-out rapidly, rapid-action, toxic side effect is small, to solve in above-mentioned background technique
The problem of proposition.
To achieve the above object, the invention provides the following technical scheme:
A kind of Jak2 inhibitor joint polygonin Alevaire, the Alevaire is by Jak2 inhibitor, polygonin and hydrotropic solvent group
At.
As a further solution of the present invention: the hydrotropic solvent includes the component of following mass fraction: 0.5%
Tween80,50% PEG8000,5% ethyl alcohol and 44.5% pure water.
A kind of preparation method of Jak2 inhibitor joint polygonin Alevaire, includes the following steps:
(1), Jak2 inhibitor is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；
(2), polygonin is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；
(3), the two is mixed later in equal volume, makes its ultimate density up to 1mg/ml.
A kind of application of the Jak2 inhibitor joint polygonin Alevaire in preparation treatment chronic bronchitis drug.
Compared with prior art, it the beneficial effects of the present invention are: the therapeutic effect to chronic bronchitis is significant, works
It fastly, and is atomization preparation, convenient drug administration.
Detailed description of the invention
Fig. 1 is blood plasma and lung group in SD rat after administration in a kind of Jak2 inhibitor joint polygonin Alevaire pharmacological evaluation
Knit TNFa, IL-1b, IL-2 in homogenate, IL-6, IL-10 level schematic diagram.
Fig. 2 is the SOD of blood plasma in SD rat after being administered in a kind of Jak2 inhibitor joint polygonin Alevaire pharmacological evaluation
With MDA testing result schematic diagram.
Fig. 3 is lung tissue in SD rat after administration in a kind of Jak2 inhibitor joint polygonin Alevaire pharmacological evaluation
SOD and MDA testing result schematic diagram.
Fig. 4 is the lung tissue dyeing that a kind of Jak2 inhibitor combines SD rat after administration in polygonin Alevaire pharmacological evaluation
Result schematic diagram.
Fig. 5 is tracheal tissue's dye that a kind of Jak2 inhibitor combines SD rat after administration in polygonin Alevaire pharmacological evaluation
Color result schematic diagram.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Please refer to figure, in the embodiment of the present invention, a kind of Jak2 inhibitor combines polygonin Alevaire, the Alevaire by
Jak2 inhibitor, polygonin and hydrotropic solvent composition, the hydrotropic solvent includes the component of following mass fraction: 0.5%
Tween80,50% PEG8000,5% ethyl alcohol and 44.5% pure water.
A kind of preparation method of Jak2 inhibitor joint polygonin Alevaire, includes the following steps:
(1), Jak2 inhibitor is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；
(2), polygonin is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；
(3), the two is mixed later in equal volume, makes its ultimate density up to 1mg/ml.
A kind of application of the Jak2 inhibitor joint polygonin Alevaire in preparation treatment chronic bronchitis drug.
Pharmacological evaluation
1) rat model of chronic bronchitis is established: injecting 200ug (200ul) in rat trachea within experiment the 1st day and the 14th day
Lipopolysaccharides, the 2-13 days, the be placed within 15-28 days after the indoor cigarette of closed cigarette smokes 0.5h and establish chronic bronchitis model.
2) SD rat is administered 30 minutes in Alevaire prepared by the present invention once a day with atomised form, dosage period
It is 15 days, while blank control group (Con group) is set, and SD rat is administered respectively: Jak2 inhibitor and polygonin, setting
For contrast groups.
3) TNFa, IL-1b, IL- in blood plasma in SD rat after the above-mentioned administration of Elisa method detection and lung homogenate are utilized
2, IL-6, IL-10 are horizontal, as a result as shown in Figure 1.
IL-10, IL-2 are anti-inflammatory factors, and IL-1 β, IL-6, TNF-a are proinflammatory factors.As can be known from the results, with control group phase
Than proinflammatory factor IL-1 β, IL-6, TNF-a level is above control group in model group, and anti-inflammatory factors IL-2 content is lower than control
Group illustrates inflammatory model modeling success.All in all, polygonum cuspidate and inhibitor individually and are used in combination and can substantially reduce IL-1
The release of β, IL-6, TNF-a inflammatory factor promotes IL-10, the release of IL-2 anti-inflammatory factors, and drug combination effect is best.
4) using superoxide dismutase activity (SOD), mda content (MDA) detection kit detection blood plasma and lung group
Superoxide dismutase activity (SOD), mda content (MDA) in homogenate are knitted, blood plasma testing result is as shown in Fig. 2, lung tissue
Testing result is as shown in Figure 3.
We detect the SOD vigor in lung tissue and serum, the results showed that, model group SOD content is substantially less than
Control group, polygonum cuspidate and inhibitor independent medication and drug combination are capable of providing the level of SOD, and it is best that effect is used in combination
MDA is the product of organism lipid oxidation, can characterize the level of lipid oxidation.We are in lung tissue and serum
MDA content is detected, the results show that model group MDA content is higher than control group, polygonum cuspidate and inhibitor independent medication and joint is used
Medicine can reduce the level of MDA, and it is best that effect is used in combination
5) lung tissue of rat and tracheal tissue row HE are dyed, inflammatory conditions, lung tissue dye is observed according to pathological analysis result
Color result is as shown in figure 4, tracheal tissue's coloration result is as shown in Figure 5.
HE has detected the inflammatory activity situation of lung tissue, as a result it is found that model group bronchus severe dilation, interstitial fibers
Change, a large amount of inflammatory cell infiltrations, polygonum cuspidate group, inhibitor group have a small amount of inflammatory cell, and compared with model group, inflammatory conditions have
Improved；Wan Tuolin and the complete happy group inflammation of love disappear substantially, meanwhile, polygonum cuspidate and inhibitor are carried out drug combination and carry out HE by us
It dyes, after polygonum cuspidate and inhibitor drug combination, alveolar structure is more complete, and substantially without inflammatory cell infiltration, inflammation improves most bright
It is aobvious.
For tracheal tissue, HE coloration result shows model group ductal ectasia, mucus gland hyperplasia, and cartilage cell's calcification is bad
It is dead obvious；After polygonum cuspidate and inhibitor independent medication, calcification situation mitigates, and mucus gland hyperplasia weakens；Polygonum cuspidate and inhibitor joint are used
After medicine, muccus gland is returned to normal, and inflammation improves most obvious.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.Any reference signs in the claims should not be construed as limiting the involved claims.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (4)
1. a kind of Jak2 inhibitor combines polygonin Alevaire, which is characterized in that the Alevaire is by Jak2 inhibitor, polygonin
It is formed with hydrotropic solvent.
2. a kind of Jak2 inhibitor according to claim 1 combines polygonin Alevaire, which is characterized in that described water-soluble molten
Agent includes the component of following mass fraction: 0.5% Tween80,50% PEG8000,5% ethyl alcohol and 44.5% pure water.
3. a kind of preparation method of Jak2 inhibitor joint polygonin Alevaire, which comprises the steps of:
(1), Jak2 inhibitor is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；
(2), polygonin is dissolved in above-mentioned hydrotropic solvent, the concentration of 2mg/ml is made；
(3), the two is mixed later in equal volume, makes its ultimate density up to 1mg/ml.
4. a kind of Jak2 inhibitor joint polygonin Alevaire as claimed in claim 1 or 2 treats chronic bronchial in preparation
Application in scorching drug.
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| CN201910478315.XA CN110151738A (en) | 2019-06-03 | 2019-06-03 | A kind of Jak2 inhibitor joint polygonin Alevaire and its preparation method and application |
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| CN201910478315.XA CN110151738A (en) | 2019-06-03 | 2019-06-03 | A kind of Jak2 inhibitor joint polygonin Alevaire and its preparation method and application |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709269A (en) * | 2005-07-08 | 2005-12-21 | 深圳海王药业有限公司 | Medicinal composition containing polydatin and its use |
| US20080261902A1 (en) * | 2005-04-04 | 2008-10-23 | Shenzhen Neptunus Pharmaceutical Co., Ltd. | Pharmaceutical composition containing polydatin and its application |
| CN101791292A (en) * | 2010-04-13 | 2010-08-04 | 江庆澜 | Application of polygonin atomizing agent as asthma-treating medicine |
| CN102482273A (en) * | 2009-06-26 | 2012-05-30 | 加拉帕戈斯股份有限公司 | 5-phenyl-[1,2,4 ]triazolo[1,5-a]pyridin-2-yl carboxamides as jak inhibitors |
| CN109833457A (en) * | 2019-02-28 | 2019-06-04 | 孟凤仙 | The application of polygonum cuspidate and turmeric and its active matter in treatment interstitial lung disease |
-
2019
- 2019-06-03 CN CN201910478315.XA patent/CN110151738A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080261902A1 (en) * | 2005-04-04 | 2008-10-23 | Shenzhen Neptunus Pharmaceutical Co., Ltd. | Pharmaceutical composition containing polydatin and its application |
| CN1709269A (en) * | 2005-07-08 | 2005-12-21 | 深圳海王药业有限公司 | Medicinal composition containing polydatin and its use |
| CN102482273A (en) * | 2009-06-26 | 2012-05-30 | 加拉帕戈斯股份有限公司 | 5-phenyl-[1,2,4 ]triazolo[1,5-a]pyridin-2-yl carboxamides as jak inhibitors |
| CN101791292A (en) * | 2010-04-13 | 2010-08-04 | 江庆澜 | Application of polygonin atomizing agent as asthma-treating medicine |
| CN109833457A (en) * | 2019-02-28 | 2019-06-04 | 孟凤仙 | The application of polygonum cuspidate and turmeric and its active matter in treatment interstitial lung disease |
Non-Patent Citations (2)
| Title |
|---|
| 王世宇: "《药用辅料学》", 30 April 2019, 中国中医药出版社 * |
| 陈思义: "《药剂学》", 28 February 1965, 人民卫生出版社 * |
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