CN106943416A - Pharmaceutical composition and its application in natural killer cell activity medicine in preparing treatment pneumonia or/and the enhancing infection of the upper respiratory tract - Google Patents
Pharmaceutical composition and its application in natural killer cell activity medicine in preparing treatment pneumonia or/and the enhancing infection of the upper respiratory tract Download PDFInfo
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- CN106943416A CN106943416A CN201710175697.XA CN201710175697A CN106943416A CN 106943416 A CN106943416 A CN 106943416A CN 201710175697 A CN201710175697 A CN 201710175697A CN 106943416 A CN106943416 A CN 106943416A
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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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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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
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
Abstract
It is a kind of pharmaceutical composition and its application in natural killer cell activity medicine in preparing treatment pneumonia or/and the enhancing infection of the upper respiratory tract the present invention relates to biomedicine technical field；Pharmaceutical composition of the present invention can be used for preparing natural killer cell activity medicine in treatment pneumonia and the enhancing infection of the upper respiratory tract；Not only murine pneumonia model caused by infected by influenza has therapeutic action to pharmaceutical composition of the present invention, it is suitable with conventional anti-viral agents Ribavirin, and pharmaceutical composition of the present invention can strengthen the NK cytoactives that mouse lung caused by influenza virus is reduced, act on suitable with existing medicine Yinqiao San；And pharmaceutical composition of the present invention to the maintenance effect of model mice body weight much better than Ribavirin and Yinqiao San, illustrate that pharmaceutical composition of the present invention has the effect for significantly improving mouse immune system function；The more existing medicine Yinqiao San of pharmaceutical composition of the present invention greatly reduces dose simultaneously, reduces production cost, and effective component is clearly, with good application prospect.
Description
Technical field
The present invention relates to biomedicine technical field, it is a kind of pharmaceutical composition and its treats pneumonia or/and increasing preparing
Application in the strong infection of the upper respiratory tract in natural killer cell activity medicine.
Background technology
Acute upper respiratory infection is caused by virus more, and infectiousness is strong, and the incidence of disease is high, easily causes outbreak of epidemic or big stream
OK.It containing the virulent spittle mainly by being propagated.Viral easily producer restructuring is reset, and produces mutant so that face
The application of bed medicine lags behind the speed of virus variation, the low or invalid phenomenon of drug therapy curative effect occurs.
Immune system is played an important role during to resisting pathogenic microbes.Research shows to improve body's immunity
The anti-virus ability of body can be strengthened.NKT（NK）Cell is the first line of defence of viral infection resisting immune defense.Cause
Be NK cells without presensitization, can direct killing virus and the target cell being infected.Therefore, occurring virus infection
When, NK cells play Immune responses of the antivirus effect earliest always prior to immunocytes such as T, B.NK is strengthened by drug therapy
Cytoactive, improves the monitoring effect of immunocyte, and then strengthens the anti-virus ability of body, and this is for caused by virus variation
Treatment is invalid important meaning.
Yinqiao San comes from written by Qing Dynasty's Wu's a kind of jade《Wen Bing Tiao Bian》, it is the representative prescription of relieving the exterior syndrome with drugs pungent in flavor and cool in property, its main function is pungent
Cool completely table, clearing heat and detoxicating, is the conventional tcm prescription of clinical treatment influenza.But existing Yinqiao San prescription taste of traditional Chinese medicine compared with
Many, dose is big, and production cost is high.
The content of the invention
The invention provides a kind of pharmaceutical composition and its prepare treatment pneumonia or/and enhancing the infection of the upper respiratory tract in from
Application in Natural killer cell active medicine, overcomes the deficiency of above-mentioned prior art, and it can effectively solve existing Yinqiao San side
Agent taste of traditional Chinese medicine is more, and dose is big, and chemical composition is indefinite, the problem of production cost is high.
One of technical scheme is realized by following measures：A kind of pharmaceutical composition, raw material is by weight
Number is made up of 4 parts to 6 parts of arctiin, 8 parts to 12 parts of Dai, 4 parts to 6 parts of glycyrrhizic acid, 1.6 parts to 2.4 parts of liquiritin.
Here is the further optimization and/or improvements to one of foregoing invention technical scheme：
Aforementioned pharmaceutical compositions raw materials by weight portion is by 5 parts of arctiin, 10 parts of Dai, 5 parts of glycyrrhizic acid, 2 parts of groups of liquiritin
Into.
Aforementioned pharmaceutical compositions are granule or capsule or pill or tablet or powder or oral agents.
The two of technical scheme are realized by following measures：A kind of pharmaceutical composition is preparing treatment lung
Application in the scorching or/and enhancing infection of the upper respiratory tract in natural killer cell activity medicine.
Pharmaceutical composition of the present invention can be used for preparing NK in treatment pneumonia and the enhancing infection of the upper respiratory tract and live
Property medicine；Not only murine pneumonia model caused by infected by influenza has therapeutic action to pharmaceutical composition of the present invention, resists with conventional
Virus drugs Ribavirin is suitable, and pharmaceutical composition of the present invention can strengthen what mouse lung caused by influenza virus was reduced
NK cytoactives, are acted on suitable with existing medicine Yinqiao San；And pharmaceutical composition of the present invention is maintained as to model mice body weight
Mouse immune system function is significantly improved with much better than Ribavirin and Yinqiao San, illustrating that pharmaceutical composition of the present invention has
Effect；The more existing medicine Yinqiao San of pharmaceutical composition of the present invention greatly reduces dose simultaneously, reduces production cost, and medicine
Definite ingredients are imitated, with good application prospect.
Brief description of the drawings
Accompanying drawing 1 is the shadow of pharmaceutical composition of the present invention and existing medicine influenza virus infected lungs NK cytoactives
Ring comparison diagram.
Embodiment
The present invention is not limited by following embodiments, can technique according to the invention scheme and actual conditions it is specific to determine
Embodiment.
Embodiment 1, the pharmaceutical composition raw materials by weight portion is by 4 parts to 6 parts of arctiin, 8 parts to 12 parts of Dai, sweet
4 parts to 6 parts of oxalic acid, 1.6 parts to 2.4 parts compositions of liquiritin.
Embodiment 2, the pharmaceutical composition raw materials by weight portion is by 4 parts or 6 parts of arctiin, 8 parts or 12 parts of Dai, sweet
4 parts or 6 parts of oxalic acid, 1.6 parts or 2.4 parts compositions of liquiritin.
Embodiment 3, as the optimization of above-described embodiment, the pharmaceutical composition raw materials by weight portion is by 5 parts of arctiin, big
10 parts of legumin, 5 parts of glycyrrhizic acid, 2 parts of compositions of liquiritin.
Embodiment 4, as the optimization of above-described embodiment, the pharmaceutical composition is granule or capsule or pill or tablet
Or powder or oral agents.Various formulations can be made according to a conventional method for pharmaceutical composition of the present invention.
Embodiment 5, pharmaceutical composition NK in treatment pneumonia or/and the enhancing infection of the upper respiratory tract is prepared
Application in active medicine.
The pharmaceutical composition that above-described embodiment is obtained is killed naturally in treatment pneumonia or/and the enhancing infection of the upper respiratory tract is prepared
The application hindered in cytoactive medicine is as follows：
1. experiment material and medicine
Flu virus A/H1N1/Puerto Rico/8/34, are abbreviated as PR8, purchased from Disease Control and Prevention in China
Center virosis prevention and control institute's influenza room, the conventional chicken embryo passage of Chinese department of traditional Chinese medicine institute biocontainment laboratory, -80 DEG C of refrigerators
Preserve.
Mouse and C57BL/6 mouse（SPF/VAF grades）, male and female half and half, body weight is 14 ± 1g, and it is dynamic to herd sun experiment by Beijing gold
Thing Technology Co., Ltd. provides, animal credit number SCXK (capital) 2014-0004.
Ribavirin is used for the prevention and treatment of respiratory viral infection disease.Resisiting influenza virus is used as in this experiment
Positive control medicine, mouse dosage is 82.5mg/kg/d.
Lenalidomide is used for the treatment of Huppert's disease；Its mechanism of action is enhancing natural killer cell activity.This reality
Test middle as the positive control medicine for improving NK cytoactives, mouse dosage is 100mg/kg/d.
Other medicines are purchased from Shanghai reagent in future Co., Ltd, including MENTHOL（Levorotatory menthol, menthol）, coffee
Acid, arctiin, pulegone（(R)-(+)-pulegone）, menthones, Dai, genistein, glycyrrhizic acid, liquiritin.
The mouse dosage of each medicine, formulates the mouse dose of this experiment in bibliography.
The screening of raw material
The screening of material medicine is shown in Table 1；In table 1 each group medicine is designed according to the horizontal quadrature of 9 factor 2；ICR mouse are pressed into body
15 groups, respectively Normal group, model group, Ribavirin group, each material medicine group are randomly divided into again（12 groups i.e. in table 1
Medicine）, every group 10, the mouse dosage of each group is 0.2mL/10g.In addition to Normal group, remaining each group is by mouse anesthesia
Afterwards, with 15 LD50Flu virus PR8 collunariums infect, every 30 μ L；Start administration in 2h after infection, press every time
0.2mL/10g gastric infusions, 1 time a day, continuous 5 days, Normal group and model group gave isometric distilled water；Treatment the
Dissected after weighing within 5 days, weigh lung weight, calculate Lung Exponent and lung index, as a result comparing t inspections between use group is counted
Handle.
Lung Exponent=lung weight in wet base (g)/body weight（g）
Lung index=（Model group lung weight-test medicine group lung weight）/（Model group lung weight-Normal group lung weight）×
100%
Therapeutic action of each group to PR8 infecting mouse pulmonary inflammation models in raw material screening（n=10）It is shown in Table 2；1 to 12 in table 2
12 groups of medicines in corresponding table 1, the result of table 2 is shown, is infected using H1N1virus PR8 after normal mouse, mouse lung
Index substantially increases, and being compared with Normal group has significant difference（P<0.01）；The infection same day, which starts to give test medicine, to be controlled
Treat 5 days, the different pharmaceutical composition group Lung Exponent tried is significantly reduced, wherein the 2nd group, the 8th group and the 11st group convection current is susceptible
The increased inhibiting rate of Lung Exponent is higher than remaining each test medicine group caused by malicious（P<0.05）；And Mouse Weight is also significantly greater than
Model group, while also above remaining each test medicine group and positive control drug Ribavirin group.Wherein the 11st group（Medicine i.e. of the present invention
Compositions）Most strong to the inhibiting rate of murine pneumonia model in all test medicines, the reduction of its Mouse Weight is also minimum, says
The bright more other each groups of pharmaceutical composition of the present invention are stronger to the inhibiting rate of pneumonia, effect more preferably, so determine raw material screening with
11st group is defined, i.e., pharmaceutical composition of the present invention（Raw material composition arctiin, Dai, glycyrrhizic acid and liquiritin）Proceed to grind
Study carefully.
What each medicine coordinated in drug regimen raw material composition arctiin of the present invention, Dai, glycyrrhizic acid and liquiritin enters
One step research
ICR mouse are randomly divided into 10 groups, respectively Normal group, model group, Ribavirin group, medicine of the present invention by body weight
Composition material fractionation group（It is split as 7 groups）, every group 10, drug regimen raw material fractionation group of the present invention（Split
For 7 groups）Proportioning be shown in Table 3；In addition to Normal group, after mouse anesthesia, with 15 LD50Flu virus
PR8 collunariums infect, every 30 μ L.Start administration in 2h after infection, 0.2mL/10g gastric infusions, 1 time a day, continuous 5 are pressed every time
My god, Normal group and model group give isometric distilled water.Treat and dissected after weighing within the 5th day, weigh lung weight, calculate lung and refer to
Number and lung index.As a result compare t between use group and examine progress statistical procedures.
Lung Exponent=lung weight in wet base (g)/body weight（g）
Lung index=（Model group lung weight-test medicine group lung weight）/（Model group lung weight-Normal group lung weight）×
100%
Normal group, model group, Ribavirin group, drug regimen raw material fractionation group of the present invention（It is split as 7 groups）It is right
The therapeutic action of PR8 infecting mouse pulmonary inflammation models（n=10）It is shown in Table 4；From table 3 and table 4 as can be seen that using H1N1
After influenza virus PR8 infection normal mouses, mouse Lung Exponent substantially increases, and being compared with Normal group has significant difference（P<
0.01）.According to the test group of orthogonal trial, it is therefore an objective to by splitting, investigate drug regimen raw material fractionation group of the present invention（Will
It is split as 7 groups）In each medicine activity.The infection same day starts the different pharmaceutical combination given test medicine treatment 5 days, tried
Thing group, in addition to the 1st group and the 2nd group, remaining each group Lung Exponent has reduction；Drug regimen raw material fractionation group of the present invention（Will
It is split as 7 groups）Inhibiting rate be respectively less than pharmaceutical composition of the present invention（Raw material composition arctiin, Dai, glycyrrhizic acid and Radix Glycyrrhizae
Glycosides）Inhibiting rate.
The influence of pharmaceutical composition influenza virus infected lungs NK cytoactives of the present invention
C57BL/6 mouse are randomly divided into 5 groups, respectively Normal group, model group, Lenalidomide group, Li Bawei by body weight
Woods group and pharmaceutical composition group of the present invention（That is arctiin+Dai+glycyrrhizic acid+liquiritin）, every group 3.Except Normal group
Outside, by after mouse anesthesia, with 15 LD50Flu virus PR8 collunariums infect, every 30 μ L.Opened in 2h after infection
Begin administration, 0.2mL/10g gastric infusions are pressed every time, 1 time a day, continuous 5 days, Normal group and model group were given isometric
Distilled water.Treat and dissected after weighing within the 5th day, win lungs, prepare lungs single cell suspension, remove red blood cell, gained is thin in vain
4 DEG C of lucifuges of born of the same parents and mouse Ly49D monoclonal antibodies and Ly49H monoclonal antibodies are incubated 30min；Isotype control group is prepared simultaneously,
Negative control group and the control of each monoclonal antibody.PBS is washed 2 times, is fixed with 4% paraformaldehyde, using flow cytomery.Knot
Fruit examines progress statistical procedures using t is compared between group.
The influence contrast of pharmaceutical composition of the present invention and existing medicine influenza virus infected lungs NK cytoactives
As shown in Figure 1, the compound combination in Fig. 1 is pharmaceutical composition of the present invention to figure（Arctiin+Dai+glycyrrhizic acid+Radix Glycyrrhizae
Glycosides）；It will be seen from figure 1 that after mouse infection influenza virus, the mono- positive NK of the mono- positive NK cells of lungs Ly49D+, Ly49H+ is thin
Born of the same parents and the double positive NK cells of Ly49D+Ly49H+ significantly lower（P<0.01）；After each group drug therapy, to NK cell surfaces
Ly49D+And Ly49H+Antigen presentation has significant facilitation（P<0.01,P<0.05）；Infected by influenza model mice lungs
NK cytoactives, pharmaceutical composition of the present invention has significant promotion activity, acts on suitable with Yinqiao San group；While existing Lonicera and Forsythia
Scattered adult's dose is 18g/ people/d, and adult's dose of pharmaceutical composition of the present invention is 1.664g/ people/d, so as to subtract significantly
Lack dose, reduce production cost.
In summary, pharmaceutical composition of the present invention can be used for preparing and be killed naturally in treatment pneumonia and the enhancing infection of the upper respiratory tract
Hinder cytoactive medicine；Not only murine pneumonia model caused by infected by influenza has therapeutic action to pharmaceutical composition of the present invention,
It is suitable with conventional anti-viral agents Ribavirin, and pharmaceutical composition of the present invention can strengthen mouse lung caused by influenza virus
The NK cytoactives of dirty reduction, are acted on suitable with existing medicine Yinqiao San；And pharmaceutical composition of the present invention is to model mice body weight
Maintenance effect much better than Ribavirin and Yinqiao San, illustrate pharmaceutical composition of the present invention have significantly improve mouse immune system
The effect for function of uniting；The more existing medicine Yinqiao San of pharmaceutical composition of the present invention greatly reduces dose simultaneously, reduces production
Cost, and effective component is clearly, with good application prospect.
Above technical characteristic constitutes embodiments of the invention, and it has stronger adaptability and implementation result, can basis
The non-essential technical characteristic of increase and decrease is actually needed, to meet the demand of different situations.
Claims (4)
1. a kind of pharmaceutical composition, it is characterised in that raw materials by weight portion is by 4 parts to 6 parts of arctiin, 8 parts to 12 of Dai
Part, 4 parts to 6 parts of glycyrrhizic acid, 1.6 parts to 2.4 parts compositions of liquiritin.
2. pharmaceutical composition according to claim 1, it is characterised in that raw materials by weight portion is by 5 parts of arctiin, soybean
10 parts of element, 5 parts of glycyrrhizic acid, 2 parts of compositions of liquiritin.
3. pharmaceutical composition according to claim 1 or 2, it is characterised in that pharmaceutical composition be granule or capsule or
Pill or tablet or powder or oral agents.
4. a kind of pharmaceutical composition according to claim 1 or 2 or 3 is preparing treatment pneumonia or/and the enhancing upper respiratory tract
Application in infection in natural killer cell activity medicine.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710175697.XA CN106943416B (en) | 2017-03-22 | 2017-03-22 | Pharmaceutical composition and application thereof in preparing medicine for treating pneumonia or/and enhancing natural killer cell activity in upper respiratory tract infection |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710175697.XA CN106943416B (en) | 2017-03-22 | 2017-03-22 | Pharmaceutical composition and application thereof in preparing medicine for treating pneumonia or/and enhancing natural killer cell activity in upper respiratory tract infection |
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| Publication Number | Publication Date |
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| CN106943416A true CN106943416A (en) | 2017-07-14 |
| CN106943416B CN106943416B (en) | 2020-04-14 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111297882A (en) * | 2020-04-20 | 2020-06-19 | 北京大学 | Application of liquiritin and derivative thereof in preparation of medicine for treating and/or preventing novel coronavirus |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1579404A (en) * | 2003-08-06 | 2005-02-16 | 孙明杰 | Novel preparation of glycyrrhizin |
| CN1965844A (en) * | 2005-11-14 | 2007-05-23 | 北京美倍他药物研究有限公司 | Nasal administered pharmaceutical composition containing glycyrrhetic acid and medical use thereof |
-
2017
- 2017-03-22 CN CN201710175697.XA patent/CN106943416B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1579404A (en) * | 2003-08-06 | 2005-02-16 | 孙明杰 | Novel preparation of glycyrrhizin |
| CN1965844A (en) * | 2005-11-14 | 2007-05-23 | 北京美倍他药物研究有限公司 | Nasal administered pharmaceutical composition containing glycyrrhetic acid and medical use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 石钺等: "银翘散抗流感病毒有效部位群化学成分的分离与鉴定", 《中国中药杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111297882A (en) * | 2020-04-20 | 2020-06-19 | 北京大学 | Application of liquiritin and derivative thereof in preparation of medicine for treating and/or preventing novel coronavirus |
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| CN106943416B (en) | 2020-04-14 |
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