CN105363019B - A kind of cyclosporine composition for treating hemolytic anemia and its application - Google Patents
A kind of cyclosporine composition for treating hemolytic anemia and its application Download PDFInfo
- Publication number
- CN105363019B CN105363019B CN201510947203.6A CN201510947203A CN105363019B CN 105363019 B CN105363019 B CN 105363019B CN 201510947203 A CN201510947203 A CN 201510947203A CN 105363019 B CN105363019 B CN 105363019B
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- CN
- China
- Prior art keywords
- hemolytic anemia
- cyclosporine
- montelukast sodium
- pharmaceutical composition
- application
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
Abstract
The invention discloses a kind of pharmaceutical composition for treating hemolytic anemia and its application, active ingredient is made of Montelukast Sodium and cyclosporine in the pharmaceutical composition, the two brings obvious coordinating effect in terms of hemolytic anemia is treated by different action target spots, Montelukast Sodium side effect at the same time and adverse reaction rate are low, cyclosporine dosage is only 1/5th of conventional amount used, therefore drug cost, side effect and adverse reaction rate are also greatly lowered, and add the security and compliance of patient medication.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular to a kind of cyclosporine composition for treating hemolytic anemia
And its application.
Background technology
Hemolytic anemia (hemolyticanemia, HA), refers to hematoclasis acceleration, and hemopoietic function of bone marrow is compensatory not
A kind of anaemia occurred when sufficient.Haemolysis (hemolysis) is that red blood cell is destroyed, the process of the lost of life.Marrow has just
The compensatory capacity of normal 6~8 times of hematopoiesis, when haemolysis exceedes the compensatory capacity of marrow, caused anaemia is hemolytic anemia；When molten
Blood occurs and marrow can be known as haemolysis state (hemolyticstate) when can be compensatory without anaemia.Hemolytic anemia it is basic
The reason is that red blood cell life span shortens, and the reason for causing hematoclasis to accelerate, can be summarized as two aspects：Red blood cell is in itself
Latent defect and red blood cell external factor are abnormal.The former is mostly haemolytic diseases, and the latter causes acquired haemolysis.Wherein, it is red thin
Born of the same parents' latent defect mainly includes erythrocyte membrane defect, red blood cell enzyme defect, globin abnormality etc..Red blood cell external factor is extremely main
To include immune sexual factor, non-immunity factor.The clinical manifestation of hemolytic anemia mainly with haemolysis process duration and
The order of severity of haemolysis is related.
At present, the common medicine for treating mankind's hemolytic anemia is glucocorticoid, it is by suppressing macrophage to antigen
Phagocytosis and processing, suppress T cell produce IL-2 and play a role.But the medicine index is not effected a permanent cure, and adverse reaction compared with
It is more, easily recurred after drug withdrawal.Recent study persons are begun attempt to using autoimmunities such as immunosuppressant treatment hemolytic anemias
Disease, obtains satisfactory results.But treat this kind of disease and generally require patient's Long-term taking medicine, and existing immunodepressant
The shortcomings that generally existing adverse reaction effect is stronger, and patient is difficult to be resistant to for a long time.Therefore, the novel immune suppression of high-efficiency low-toxicity is developed
Preparation is still the important topic of pharmaceutical research.
The content of the invention
The present inventor is found surprisingly that Montelukast Sodium shows a degree of anti-hemolysis anaemia in clinical application
Drug effect.Based on this research, the present invention has done the discovery further animal experiment research, finds Montelukast Sodium commissural arch
Spore element shows unexpected synergistic effect in terms of hemolytic anemia animal model is treated.
Therefore, it is an object of the invention to provide a kind of pharmaceutical composition for treating hemolytic anemia and its application.Specifically
Ground, the object of the present invention is achieved like this：
A kind of pharmaceutical composition for treating hemolytic anemia, wherein active ingredient is by Meng Lusi in the pharmaceutical composition
Special sodium and cyclosporine composition.Pharmaceutical composition of the present invention largely solves the single use of cyclosporine by drug combination
The contradiction for making patient be difficult between the more serious adverse reaction being resistant to and the treatment that must be carried out for a long time caused by medicine.
Preferably, the pharmaceutical composition of hemolytic anemia is treated as described above, wherein Meng Lusi in the active ingredient
The weight consumption ratio of special sodium and cyclosporine is (0.1~0.5)：1.
It is further preferred that the pharmaceutical composition of hemolytic anemia is treated as described above, wherein in the active ingredient
The weight consumption of Montelukast Sodium and cyclosporine ratio is (0.2~0.3)：1.
Still further preferably, the pharmaceutical composition of hemolytic anemia is treated as described above, wherein the active ingredient
The weight consumption ratio of middle Montelukast Sodium and cyclosporine is 0.25：1.
The pharmaceutical composition for the treatment of hemolytic anemia of the present invention can play drug effect after being administered orally, therefore will
It is prepared as oral formulations, and the oral formulations include capsule (such as soft capsule), tablet, granule.
It is further preferred that treating the pharmaceutical composition of hemolytic anemia as described above, contain Meng Lu in per unit preparation
The special sodium 1-2.5mg of department, and cyclosporine 5-10mg.
Hemolytic anemia animal model, at present relatively it is generally accepted that the red blood cell hematopoiesis using acetylphenylhydrazine induction damages mould
Type.The present inventor has been successfully, reproduced hemolytic anemia model using rat through acetylphenylhydrazine is injected intraperitoneally, and is controlled using different pharmaceutical
The hemolytic anemia of rat is treated, observation of curative effect is carried out by hemolytic anemia items Anemia, it turns out that, with model comparison
Group compares, and each administration group Rat Erythrocytes, hemoglobin, packed cell volume level have raised, and difference is anticipated with statistics
Adopted (P ＜ 0.05)；Compared with each single medicine group (MK groups, CSA groups), MK-CSA groups Rat Erythrocytes, hemoglobin and red blood cell pressure
Ponding pingxian writes rise (P ＜ 0.05), and shows Montelukast Sodium and synergistic effect associated with cyclosporine.Therefore, it is of the invention
A kind of pharmaceutical applications are also provided, i.e.,：Application of the Montelukast Sodium in the medicine for preparing treatment hemolytic anemia, and Meng Lusi
Application of the active ingredient of special sodium and cyclosporine composition in the medicine for preparing treatment hemolytic anemia.
Compared with prior art, in pharmaceutical composition provided by the invention active ingredient by Montelukast Sodium and low dosage
Cyclosporine forms, the two brings obvious coordinating effect in terms of hemolytic anemia is treated by different action target spots, together
When Montelukast Sodium side effect and adverse reaction rate it is low, cyclosporine dosage is only 1/5th of conventional amount used, therefore medication
Expense, side effect and adverse reaction rate are also greatly lowered, and add the security and compliance of patient medication.
Embodiment
The invention will now be further described with reference to specific embodiments, technique effect of the invention will be with description and more
To be clear.It should be understood that the embodiment is only exemplary, any restrictions are not formed to protection scope of the present invention.Ability
Field technique personnel should be understood that and the details and form of technical solution can be repaiied without departing from the spirit of the invention
Change or replace, but these modifications or substitutions each fall within protection scope of the present invention.
1 Montelukast Sodium of embodiment joint cyclosporine tests the effect of hemolytic anemia rat model
Wistar rats 50,180~220g of weight.Rearing conditions：Room temperature at 20~25 DEG C, relative humidity for 38%~
41%, artificial light, each 12h of light and shade, for solid normal diet and tap water, drinking-water of freely ingesting, good ventilation；Sweep daily
Indoor sanitation 2 times, keeps indoor without obvious ammonia odor taste.
50 rats are randomly divided into following five groups：Normal group, model control group, MK groups, CSA groups, MK-CSA groups,
Every group of 10 rats, half male and half female.Rat adaptability is fed after a week, in addition to Normal group, other each groups at first day and
2% acetylphenylhydrazine normal saline solution 0.2g/kg, Normal group intraperitoneal injection of saline generation are injected intraperitoneally within 4th day respectively
Replace.The same day starts to be administered after modeling success, MK group gavage montestron sodium 0.9mg/kg, CSA group gavage cyclosporine 8mg/kg,
MK-CSA group gavage montestron sodium 0.5mg/kg and cyclosporine 2mg/kg, successive administration 7 days, while Normal group and model
Control group gavages physiological saline.When after last time is administered 24 is small, Culling heart blood, detection red blood cell, hemoglobin, red blood cell
Hematocrit.The testing result of each index is shown in Table 1 after mathematical statistics.
Can be seen that by the result of the test of table 1 compared with Normal group, model group rats red blood cell, hemoglobin,
Packed cell volume significantly reduces (P ＜ 0.05), shows that hemolytic anemia model is successfully prepared.Compared with model control group, respectively
Administration group Rat Erythrocytes, hemoglobin, packed cell volume level have raised, and difference has statistical significance (P ＜
0.05).Especially, compared with each single medicine group (MK groups, CSA groups), MK-CSA groups Rat Erythrocytes, hemoglobin and red blood cell pressure
Ponding pingxian writes rise (P ＜ 0.05), and shows Montelukast Sodium and synergistic effect associated with cyclosporine.
1 each group Rat Erythrocytes of table, hemoglobin, packed cell volume are horizontal relatively
Note：Compared with model control group,*P ＜ 0.05；MK-CSA groups compared with MK groups,#P ＜ 0.05；MK-CSA groups and CSA
Group compares,$P ＜ 0.05.
In addition, weighing before and after experiment to rat weight, and observe the general state of rat, the results show：The body of CSA groups
Quality substantially reduces, and rat shows apathetic, spiritlessness and weakness, easily frightened, is slow in action, and group's contracting is bended over, lip, eyelid,
Auricle is pale, easily depilation, the fluffy perpendicular few gloss of hair；Drinking a lot of water, feed are reduced, and stool is dry black and lacks.And the constitution of other group of rat
Amount increase, the state of mind recover preferable, and rat manner is strong and vigorous, and Quick off the mark, eyes become clear, in shocking pink, the clean tide of muffle
Profit is in rose pink, and tail circle toner is red, and back of the body waist is straight, hair gloss and it is close, stool is yellow soft.
Claims (2)
1. it is by weight by Montelukast Sodium and cyclosporine（0.1~0.5）：The active ingredient of 1 composition is preparing treatment haemolysis
Applied in the medicine of property anaemia, the medicine is oral formulations.
2. it is by weight by Montelukast Sodium and cyclosporine according to claim 1（0.1~0.5）：1 composition activity into
Point prepare treatment hemolytic anemia medicine in apply, it is characterised in that the oral formulations be selected from capsule, tablet,
Granule.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510947203.6A CN105363019B (en) | 2015-12-16 | 2015-12-16 | A kind of cyclosporine composition for treating hemolytic anemia and its application |
| CN201810203121.4A CN108273039B (en) | 2015-12-16 | 2015-12-16 | Pharmaceutical composition for treating hemolytic anemia and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510947203.6A CN105363019B (en) | 2015-12-16 | 2015-12-16 | A kind of cyclosporine composition for treating hemolytic anemia and its application |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810203121.4A Division CN108273039B (en) | 2015-12-16 | 2015-12-16 | Pharmaceutical composition for treating hemolytic anemia and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105363019A CN105363019A (en) | 2016-03-02 |
| CN105363019B true CN105363019B (en) | 2018-04-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510947203.6A Active CN105363019B (en) | 2015-12-16 | 2015-12-16 | A kind of cyclosporine composition for treating hemolytic anemia and its application |
| CN201810203121.4A Expired - Fee Related CN108273039B (en) | 2015-12-16 | 2015-12-16 | Pharmaceutical composition for treating hemolytic anemia and application thereof |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201810203121.4A Expired - Fee Related CN108273039B (en) | 2015-12-16 | 2015-12-16 | Pharmaceutical composition for treating hemolytic anemia and application thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1061407A (en) * | 1990-10-12 | 1992-05-27 | 麦克弗罗斯特(加拿大)有限公司 | Unsaturated hydroxyalkyl quinoline carboxylic acid as the leukotrienes antagonist |
| EP1229034A1 (en) * | 2001-01-31 | 2002-08-07 | Pfizer Products Inc. | Nicotinamide derivatives and their mimetics as inhibitors of PDE4 isozymes |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1269844C (en) * | 2003-03-14 | 2006-08-16 | 中国药科大学 | Chitin derivative and its preparation and its uses in preparation of medicines |
| US9364507B2 (en) * | 2009-08-11 | 2016-06-14 | Imagilin Technology, Llc | Probiotic enhancement of steroid and immune suppressor activity in mammals with chronic diseases |
-
2015
- 2015-12-16 CN CN201510947203.6A patent/CN105363019B/en active Active
- 2015-12-16 CN CN201810203121.4A patent/CN108273039B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1061407A (en) * | 1990-10-12 | 1992-05-27 | 麦克弗罗斯特(加拿大)有限公司 | Unsaturated hydroxyalkyl quinoline carboxylic acid as the leukotrienes antagonist |
| EP1229034A1 (en) * | 2001-01-31 | 2002-08-07 | Pfizer Products Inc. | Nicotinamide derivatives and their mimetics as inhibitors of PDE4 isozymes |
Non-Patent Citations (3)
| Title |
|---|
| Autoimmune-Hemolytic Anemia Associated With Montelukast and Zafirlukast Therapy in a Patient With Hepatitis C;Kurt A. Wargo,et al;《Hospital Pharmacy》;20080430;第43卷(第4期);300-302,306 * |
| 慢性特发性荨麻疹的药物治疗进展;尚淑贤等;《国外医学皮肤性病学分册》;20050930;第31卷(第5期);274-276 * |
| 来氟米特对小鼠实验性自身溶血性贫血的作用及其与环孢素的协同作用研究;常秦等;《中国抗生素杂志》;20030131;第28卷(第1期);45-47 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108273039A (en) | 2018-07-13 |
| CN108273039B (en) | 2021-04-30 |
| CN105363019A (en) | 2016-03-02 |
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| CB03 | Change of inventor or designer information |
Inventor after: Li Jingdong Inventor after: Yang Cui Inventor after: Ma Dong Inventor after: Huang Yan Inventor after: Li Ang Inventor before: Han Xiaolin Inventor before: Li Jingdong Inventor before: Wang Wanling Inventor before: Yang Cui |
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