CN107115334A - A kind of pharmaceutical composition for treating immunity miscarriage - Google Patents
A kind of pharmaceutical composition for treating immunity miscarriage Download PDFInfo
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- CN107115334A CN107115334A CN201710125498.8A CN201710125498A CN107115334A CN 107115334 A CN107115334 A CN 107115334A CN 201710125498 A CN201710125498 A CN 201710125498A CN 107115334 A CN107115334 A CN 107115334A
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- miscarriage
- pharmaceutical composition
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- 0 *=C(CC1)CCC1C(CF)=O Chemical compound *=C(CC1)CCC1C(CF)=O 0.000 description 1
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- Health & Medical Sciences (AREA)
- Emergency Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition for treating immunity miscarriage, the carrier and auxiliary material that described pharmaceutical composition is commonly used by a certain amount of active drug composition and pharmaceutically are constituted, and the structure of wherein active drug composition is：
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to a kind of pharmaceutical composition for treating immunity miscarriage.
Background technology
Spontaneous abortion is the common complication of First Trimester, and incidence accounts for the 15-20% of all gestation, threatens mother and baby to be good for
Health and social stability.In recent years, rate of spontaneous abortion presents the variation tendency risen year by year in the whole world, causes domestic and foreign scholars
Deepest concern.Due to two current child's policies of China, the quantity of the couple at child-bearing age is particularly considerable, therefore researches and develops anti-women spontaneous abortion
Medicine for treat and prevent immunity spontaneous abortion for it is very urgent.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for treating immunity miscarriage.
In order to realize the purpose of the present invention, the present invention provides a kind of pharmaceutical composition for treating immunity miscarriage, the medicine
The carrier and auxiliary material that compositions are commonly used by a certain amount of active drug composition and pharmaceutically are constituted.Wherein active drug composition
Structure be：
Wherein
R1 independently selected from：H, alkyl or halogen；
Preferably, R1 is F.
It is highly preferred that the content of the active drug composition is 18-28mg.
It is highly preferred that described pharmaceutical composition can be formulation described in any pharmacy
The present invention also provides purposes of the compound in the medicine for preparing treatment immunity miscarriage, under the compound has
Array structure：
Wherein
R1 independently selected from：H, alkyl or halogen；
Preferably, R1 is F.
From therapeutic effect, the pharmaceutical composition for the treatment of immunity miscarriage of the present invention has anti-immune certainly
The effect so miscarried, using can be reduced after medicine pregnant woman occur spontaneous abortion possibility, be treatment immunity miscarriage compared with
For satisfied medicine.From mechanism of action, medicine of the present invention has special for the Prevention that LADA is miscarried
Property strong, the high superiority of sensitivity.
Embodiment
Detailed elaboration is made to the present invention by the following examples, medicine of the present invention is determined in model mice placenta tissue
The influence of key molecule signal transduction, the mechanism of action and last therapeutic effect of medicine of the present invention are disclosed from immune angle.
The sign of the medicine of the present invention of experimental example 1
1H NMR(CDCl3,300MHz)δ4.96(s,1H),4.80(s,1H),3.67(s,3H),2.69-2.61(m,1H),
2.33-2.24(m,1H),2.11-2.07(m,2H),1.99-1.95(m,2H),1.58-1.34(m,4H)。
The therapeutic effect that the medicine of the present invention of experimental example 2 is miscarried for immunity
Packet, modeling and administration
It is 6 groups, respectively every group 10, blank control group, model group, Ah Si at random by 60 female BAl BIcs/c mouse
Woods group (positive control, 20mg/mL) and the basic, normal, high dosage group of medicine of the present invention (dosage is respectively 10,20,40mg/
mL).In addition to blank control group, remaining each group mouse reference literature (Tolomeo T, Rico De Souza A, Roter E, et
al.T cells demonstrate a Th1-biased response to native beta2-glycoprot ein I
in a murine model of anti-phospholipid antibody induction[J].Autoimmunity,
2009,42(4)：Method is with people β in 292-295.)2It is small that-glycoprotein I sets up anti-phospholipid antibody (APA) positive miscarriage for immunogene
Mouse model：By β2- glycoprotein I is dissolved in sterile phosphate buffer (PBS), and adjustment mass concentration is 400 μ g/mL.From experiment
Start ip people β within 1st day2- glycoprotein I is 1 with Freund's complete adjuvant (CFA) volume ratio：The 1 μ L of mixed liquor 50；Test the 8th day with
Incomplete Freund's adjuvant (IFA) replaces CFA booster immunizations 1 time, and dosage is immunized with the 1st time.In experiment the 18th day, each group ♀ mouse
With ♂ mouse with 2：1 ratio is mated, from mating certainly, every morning 8：00 and afternoon 14：00 observes 1 time respectively, if observation
A large amount of sperms are accompanied into keratinocyte and/or cloudy bolt is seen and are then calculated as gestation the 0.5th day.Each administration group from pregnant 1st day
Mouse is administered by 0.1mL/10g ig, blank control group and the isometric distilled water of model group mouse ig, 1 time a day, continuous 9d.
Gestation the 9.5th day when cervical dislocation put to death mouse, leave and take placenta tissue carry out index of correlation measure.
RT-PCR methods determine mouse placenta tissue Toll-like receptor 4 (TLR4), myeloid differentiation-2 (MD2), the differentiation of marrow sample
The factor 88 (MyD88), nuclear factor (NF- κ B) mRNA expressions
The placenta tissue shredded is handled using Trizol liquid and total serum IgE is extracted, is carried out according to reverse transcription reagent box specification
Reverse transcription synthesizes cDNA, is expanded by masterplate of cDNA.Reaction system：Real-time PCR Master Mix mixed liquors 10
μ L, each μ L of 0.4 μ L, cDNA template 2 of upstream and downstream primer, sterilize the μ L of distilled water 7.2, system totally 20 μ L.In the semidefinite of gene expression
In amount analysis, with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for internal reference, testing gene is realized by being compared with GAPDH expression quantity
The standardization of expression quantity.Reaction condition：The amplification stage is 95 DEG C of 5min；95℃15s；60 DEG C of 60s, totally 40 circulations；Dissolving is bent
The line stage is 95 DEG C of 15s；60℃1min；95℃15s.Software is carried with RT-PCR systems and carries out solubility curve analysis, with 2-ΔΔCt
(Li Shasha, Zhang Yijun, Li Hongli wait detection [J] China of MTAP albumen and gene expression dose in non-small cell carcinomas swollen to method
Knurl magazine, 2011,14 (2)：151-155.) calculate target gene mRNA relative expression quantity.Gene primer sequence and product are long
Degree see the table below.
Immunohistochemical Method determines mouse placenta tissue TLR4, MD2, MyD88, NF- kB protein expression
It is conventional to prepare mouse placenta tissue paraffin section.Conventional dewaxing, dehydration, PBS are rinsed 3 times, each 3min；3% pair
Oxygen water (H2O2) normal temperature be incubated 15min, PBS rinse 3 times, each 3min；Add after 3% bovine serum albumin(BSA) (BSA) closing 30min
Enter corresponding primary antibody, 4 DEG C of overnight incubations of wet box, PBS is rinsed 3 times, each 5min；Add the secondary antibody of 50 μ L biotin labelings, room temperature
20min is incubated, PBS is rinsed 3 times, each 5min；Plus the streptomysin avidin working solution of horseradish peroxidase-labeled, room temperature incubates
Educate PBS after 20min to rinse 3 times, each 5min；Diaminobenzidine (DAB) nitrite ion is added, develop the color 2~5min, mirror at room temperature
Lower control；Haematoxylin redyeing, conventional dehydration, transparent, mounting.Positive products are positioned at cytoplasm, with cytoplasm coloring in palm fibre
Brown is positive cell.TLR4, MD2, MyD88, NF- κ B integral optical density are analyzed with computer image analysis software (IPP)
(IOD) value, the power of positive expression is reflected with this.
Statistical method
Statistical analysis is carried out using the softwares of SPSS 10.0.Data withRepresent, compare between group using single factor test variance point
Analysis.P ＜ 0.05 represent that difference is statistically significant.
Each group mouse placenta tissue TLR4, MD2, MyD88, NF- κ B mRNA expression measurement results
Compared with blank control group, model group mouse placenta tissue TLR4, MD2, MyD88, NF- κ B mRNA expressions
Significantly raised (P ＜ 0.01)；Compared with model group, aspirin group and medicine low dose group mouse placenta tissue of the present invention
TLR4, MD2, MyD88, NF- κ B mRNA expressions substantially reduce (P ＜ 0.01), medicine middle dose group mouse tire of the present invention
Disk tissue T LR4, MD2, MyD88mRNA expression reduce (P ＜ 0.05 or P ＜ 0.01), and medicine high dose group of the present invention is above-mentioned
Not statistically significant (the P of indicator difference>0.05)；Compared with aspirin group, medicine low dose group mouse placenta group of the present invention
Knit the reduction of TLR4, MD2, MyD88, NF- κ B mRNA expressions to become apparent, wherein TLR4, MD2mRNA expression difference
Statistically significant (P ＜ 0.01), concrete outcome see the table below.
Note：Compared with blank control group,**P<0.01；Compared with model group,#P<0.05,##P<0.01；With aspirin group
Compare,ΔΔP<0.01。
Each group mouse placenta tissue TLR4, MD2, MyD88, NF- kB protein expression measurement result
Compared with blank control group, model group mouse placenta tissue TLR4, MD2, MyD88, NF- kB protein expression is bright
Aobvious rise (P ＜ 0.01)；Compared with model group, each administration group mouse placenta tissue TLR4, MD2, MyD88, NF- kB protein expression
Level is reduced to some extent, except medicine high dose group mouse placenta tissue MD2, MyD88 protein expression level of the present invention reduction
Remaining significantly not outer each group difference is statistically significant (P ＜ 0.05 or P ＜ 0.01)；Compared with aspirin group, the present invention
MD2, MyD88 expression substantially reduce (P ＜ 0.05) in medicine low dose group mouse placenta tissue, and specific data see the table below.
Note：Compared with blank control group,**P ＜ 0.01；Compared with model group,#P<0.05,##P<0.01；With aspirin
Group compares,ΔP<0.05。
Claims (7)
1. a kind of pharmaceutical composition for treating immunity miscarriage, it is characterised in that described pharmaceutical composition is by a certain amount of effective
Drug ingedient and pharmaceutically conventional carrier and auxiliary material composition.
2. the pharmaceutical composition for the treatment of immunity miscarriage according to claim 1, it is characterised in that described a certain amount of have
The structure for imitating drug ingedient is as follows：
Wherein
R1 independently selected from：H, alkyl or halogen.
3. the pharmaceutical composition for the treatment of immunity miscarriage according to claim 2, it is characterised in that R1 is F.
4. it is according to claim 3 treatment immunity miscarriage pharmaceutical composition, it is characterised in that the active drug into
The content divided is 18-28mg.
5. the pharmaceutical composition for the treatment of immunity miscarriage according to claim 4, it is characterised in that described pharmaceutical composition
It can be formulation described in any pharmacy.
6. purposes of the compound in the medicine for preparing treatment immunity miscarriage, it is characterised in that the compound has following
Structure：
Wherein
R1 independently selected from：H, alkyl or halogen.
7. purposes according to claim 6, it is characterised in that R1 is F.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710125498.8A CN107115334A (en) | 2017-03-04 | 2017-03-04 | A kind of pharmaceutical composition for treating immunity miscarriage |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710125498.8A CN107115334A (en) | 2017-03-04 | 2017-03-04 | A kind of pharmaceutical composition for treating immunity miscarriage |
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| Publication Number | Publication Date |
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| CN107115334A true CN107115334A (en) | 2017-09-01 |
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ID=59717936
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| CN201710125498.8A Withdrawn CN107115334A (en) | 2017-03-04 | 2017-03-04 | A kind of pharmaceutical composition for treating immunity miscarriage |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030004137A1 (en) * | 1997-02-19 | 2003-01-02 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| JP2014227401A (en) * | 2013-05-24 | 2014-12-08 | 大日本住友製薬株式会社 | Phenylalanine derivative |
| CN104640843A (en) * | 2012-07-19 | 2015-05-20 | 大日本住友制药株式会社 | 1-(cycloalkyl-carbonyl)proline derivative |
| CN106103453A (en) * | 2014-01-14 | 2016-11-09 | 大日本住友制药株式会社 | It is condensed 5 oxazolidinone derivatives |
-
2017
- 2017-03-04 CN CN201710125498.8A patent/CN107115334A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030004137A1 (en) * | 1997-02-19 | 2003-01-02 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| CN104640843A (en) * | 2012-07-19 | 2015-05-20 | 大日本住友制药株式会社 | 1-(cycloalkyl-carbonyl)proline derivative |
| JP2014227401A (en) * | 2013-05-24 | 2014-12-08 | 大日本住友製薬株式会社 | Phenylalanine derivative |
| CN106103453A (en) * | 2014-01-14 | 2016-11-09 | 大日本住友制药株式会社 | It is condensed 5 oxazolidinone derivatives |
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Application publication date: 20170901 |