WO2010142167A1 - New use of carboxyamidotriazole compounds or salts thereof in the preparation of the medicaments for preventing and treating interstitial pneumonia or pulmonary fibrosis - Google Patents

Abstract

The present invention provides the use of carboxyamidotriazole or pharmaceutically acceptable salts, analogues or derivatives thereof in the preparation of the medicaments for preventing or treating interstitial pneumonia or pulmonary fibrosis. The interstitial pneumonia or pulmonary fibrosis includes lithicosis, sarcoid, allergic pneumonia, drug-induced pneumonia, radiation pneumonia, infection, fibrosing alveolitis related to collagen vascular diseases. The present invention also provides the drug kits comprising the carboxyamidotriazole compounds.

Description

 New use of chemicals

 Wood involves ca boxya do azo e CA or a new use of acceptable, analogous or derivative substances, especially in the prevention or treatment of pneumonia.休木 relates to compositions and uses containing or acceptable derivatives, derivatives

Background

 The same as anti-neoplastic pneumonia and the same anti-sex lung disease, sexual lung disease, etc., the opposite of the alveolar and peripheral support kan's inflammation. It is more than a hundred diseases. You have a small number of known causes, such as life, physical pneumonia, radiation pneumonitis, infectious diseases, etc., but some of the causes are unknown, such as special lungs. With pneumonia, you are pneumonia, but the main deficiency is caused by infections of bacteria, viruses and other micro-organisms. The alveoli and the same reversal invade the alveoli, and the accessible lungs are reciprocal. In bed, breathing, charcoal, and so on. Others are accompanied by symptoms of systemic diseases such as neoplasia, increased cell X, and the like. In functional examinations, it is possible to restrict, hypoxemia in the chest X image, and the honeycomb to the most respiratory failure and death. Prophylactic and adverse diseases with anti-neoplastic pneumonia Before the satisfactory method The 5-year survival is less than 50%.

One of the diseases of Hugh is to inhale a large number of systemic diseases caused by the formation of a large number of oxidized S particles. The oxidization of 10,000 is present in most rocks, especially the quartz dioxide is 9% higher. , quarrying, gravel, workers working in glass, ceramics, enamel, inhalable Everything is very high. Because of the lack of reliable and effective methods for the prevention and treatment of the lungs, even if it is alive, the current health care, the highest rate, the fastest, the most. The disease 5 is not yet known but there are more than 200 workers at risk.

 The morbidity rate in the exhibition was 7.1 54.6%. Dioxide leads to the formation of the same and the same reaction. Many

 Foot multicellular alveolar cells, alveolar epithelial cells, cells, lymphocytes, etc., cells and anti-chronic inflammation

10.

 A disease in which lung inflammation, alveolar, extracellular antiretroviral, and sporadic proliferation, normality, and loss of function are caused by many factors such as poison, autoimmune disease, anti-infection, and infection. Symptoms, breathing 15 illness can be the same as pneumonia.

 In the same anti-pneumonia, the West is anti-hormonal and immunosuppressive, but the effect is reversed and it is easy to cause depression, worsening of the condition or accompanied by excessive sweating. Especially in chronic cases, anti-hormones. Yes

20 Studies have reduced chemical and synthetic exposure to S, but the population is currently well. Therefore, there are better and more effective and effective diseases that are better and more effective.

25 There are wood compounds such as advanced lung cancer, ovary, large o C. .C . O co. 1997 15: 1985 1993 akea .C . O co.2003 21:4356-4363 In addition to acute and chronic inflammation of cells, Immune inflammation or other immune phase disease also has a good effect e Ge a . hm co. x . e 30 2008 325: 0 16 . However, there are currently no compounds that can be used to prevent and treat pneumonia, or disease. Muming people and in-depth research and its new use of similar things, it can improve the symptoms of the disease and can be prevented with the same anti-pneumonia. content

 The first group of woods aims to provide new uses for compounds. The foot of the wooden foot is provided in each of the symptoms of prevention and/or counter-pneumonia.

 The resting foot provides usable, analogous, or derivative agents in each of the prophylactic and/or anti-neoplastic pneumonia symptoms.

 The three feet of the eye are provided in each prevention and / or.

 The resting foot provides usable, analogous or derivative in each of the preventions and/or properties.

 The resting foot is provided in various preventive and/or inflammatory diseases.

 The resting foot provides usable, analogous or derivative agents in various preventive and/or inflammatory conditions.

 The purpose of completing the wood is provided by the following wood scheme

 Wood used or available for use in prevention and/or counter-pneumonia, the disease of which has a compound of 1

Where R has 11

In the foot of p

X may be sufficient for S SO S CO C C C or C , wherein R is derived from the amino group of C C6 of oxyamino C C6 of oxygen C C6 or

 And R respectively from halogen C C6 nitro group C C6 C C6 oxycarboxy amino C C6 C C6 vinyl chloride

 Kezheng or

 From amino C C6 amino amino amino

 Amino or

 R from amino or . In the foot 11 of the Xishu scheme, 0 1 or 2 P is equal to 1 X foot O S O or C foot

 Oxycarbonoxy nitro or vinyl chloride R

 Ethylene or nitro.

 In another scheme, it has the following 1

1

 Where X feet C S, O or CO R feet C CF B or C R feet C B or O

 The rest of the wood can be 5 1 [35 44 benzo 123 4 benzene.

 Wood includes useful, imaginable or derivative organisms.

 The available ones include sulfuric acid and acetic acid.

 In other words, the compounds in the wood include

 Compound

 1

 Where R has 1 pig

 u

 Where X of the foot 0 to 4 can be sufficient for S SO S CO C C C or C R

 Wherein R can be a sufficient oxygen C C6 C C6 oxyamino amino C C6 amino amino or

 And R can be separated by halogen C C6

Nitro C C6 C C6 oxy carbon

 Oxyamino amino C C6 C C6

Chlorovinyl positive Foot amino C C6 aminoamino amino

 Amino or

 R is an amino group or . 2 wood wood plan wood compound compound force 11 5 neutral and 0 1 or 2 P equal 1 X foot O S O or C

 Oxygen oxy, nitro or vinyl chloride

 R is ethylene or nitro.

 3. Wood wood plan

 And E

 X foot C S O or CO R foot C CF B or C R foot C B or O

5 4. Wood 1 Compound Force 5 1 [35 44 Benzene 123 4 Benzene

 Aboxya do azoe you CA

 Wood compounds also include compounds such as sulfuric acid

0 Mu Baixian proposed the compound in various prevention and / or counter-pneumonia, disease. Among them, the same anti-neoplastic pneumonia and plaque include but not sensitive pneumonia or radiation pneumonia infection vascular disease, such as alveolar alveolar. The second group of wood aims to provide a way to treat people with pneumonia or phlegm. The method comprises the steps of comprising a composition comprising an active and an acceptable acceptable composition wherein the active wood consists of 5 1 [35 44 phenyl 123 4 benzene and is acceptable, analogous, derivative thereof. In the regimen, the composition of the same anti-neoplastic pneumonia, chemotherapeutic self-administered is g or acceptable, like, derivative.

 The rest of the disease and other factors used include other factors, including, rest, health status, degree of symptoms, frequency of follow-up, and whether or not the same period is accompanied by others. The wood-like method known to the wood man can be easily used for the active compound. Adults are usually within g 2 g of g g solids. For example, a compound of 5 g g of wood can be administered orally to someone.

 A third group of woods aims to provide a composition comprising a compound of wood. For the rest of the life, it is possible to use a composition of the compound which is well known in the wood field, which is well known in the wood field.

 The compositions comprising the compound are generally, but not limited to, topical, oral, intravenous, internal, internal, internal, internal, intraventricular, subcutaneous, intraperitoneal, internal, local , under or hundred ways. Oral preparation can be sufficient to make a solution, such as granules, or a solution, or the like. Oral administration may contain an acceptable rest or form. Acceptable living or resting or shaped may be sufficient, for example, Arabic, dextrin, , ethylene, diluted lactose, sucrose, nectar, corn, phosphoric acid, , , , , , talc, Water, such as corn, ,

, , and solid dispersion of 4000 PEG4000, 6000 PEG 000 Ethylene VP and Pooxa e urea, with,,, and oxygen, as well as dextrorotatory, lactose, sucrose, and acetic acid, etc. The combination of a resting solution or an acceptable upper 5 can be sufficient, for example, aqueous water, arabic, , , , , , surface active, glycerin, and non-aqueous 400, glycerin, vegetable oil. In addition, the system may contain preservative benzo, benzo, and/or.

 External use can include topical, ointment, and the like.

 Wood provides an ingredient comprising one or more containers or a container filled with or multi-wood composition.

 Of or relating to the use of a sacred or multi-sacred wood

 Contained or usable containers and conditions of use.

 The plan wood is provided by the person. A compound containing or more than wood in the scheme.

 It can be packaged in individual containers such as water bottles, traces 0, etc. It can include usage conditions. 1 The image of cells in alveolar lavage BA F in a large quartz model

5 2 The image of the amount of cells in the alveolar lavage BA F of the large quartz model

 3 The image of lymphocytes in alveolar lavage BA F in a large quartz model

 4 The image of neutral cells in the alveolar lavage 0 BA F of the large quartz model

5 The effect of PS on the release of PS in CA R8 3 cells 6 The release of TF by PS stimulation in CA R8383 cells 7 The way of PS stimulation release of CA R8383 cells

 The following will understand and understand the wood scheme of wood. However, the wood field can easily understand the materials and compositions of Hugh. This makes a change. However, the wood plan of the wood is not limited to the solidification of the wood content.

 t

 A

 Methods Wsa Large Male and Female 170 200 9 Anesthetized tube was injected with high-vapor disinfection of 5% fine quartz physiological water / only 2 was added to the large tube to allow even distribution of the tube to the lungs. The normal 4 her death 3 made the naked eye can be in the distribution of grayish white or taupe sickness 100 to 0.1 0.3 C

 Unclear conditions Initial illness has been successful. The gender balance is divided into 3 10 models, CA low, CA high, respectively, daily water, CA g / kg CA 4 g / kg are 2 / kg. Another normal period but not equal capacity water. 6 5 she was fixed on the hijacked shelf and exposed to the upper eye ophthalmology a small opening inserted with a tube fixed

 Inject the physiological chlorinated solution into the lavage and collect the alveolar lavage BA F 5 / only. 300 p 10,000 10 over 4 and its broken in the branch cell

 The stained cells are divided into cells, lymphocytes and neutral cells.

-4 shows that the cells, cells, lymphocytes and neutrophils of the model are higher than normal. The model is normal compared with the plated AA <0.01 CA and 1 g/kg lower. The cells, cells and neutrophils were lower than the model. *<0.05 CA 40 g/kg of cells, cells, lymphocytes and neutrophils were lower than the model cells and neutrophils* < .01 Cells and lymphocytes* <0.05 1 4

 It can be seen that she can inhibit the inflammatory cells in BA F.

 2 The copper content of the large quartz model and the shadow of the pathological sheep

 Method Model making and her method are the same. 12 The hydrolysis method of her death a s e a J. C. ves. 99: 6086171997 The acid content. Yimu

 E staining.

 CA inhibits the increase in the content caused by quartz. The degree of inhibition depends on 1 . The inhibition of CA g/kg and CA 4 g/kg was calculated by the inhibition of the quartz model, 0% normal, large inhibition, and 100% inhibition. Each major E staining is normal

 Models of large alveolar alveolar can form a large number of different sizes of people with a large number of 11 V fused to the central part. The degree of CA enlargement has not been reduced to 1 士.

 The inhibition of the content of CA quartz large model

 Inhibit %

 S +CA g/kg 27.4

 S +CA 40 g/kg 39.2 3 Animals Alveolar cells release O shadow

The method uses extracellular R8 3 cells derived from large alveolar cells. Will R8 3 cells x. 'Connected to 24 /? The cells are good at night. 4

 1 normal does not pick up and PS force blank

 2 PS Add PS g to it. And S work 3 CA low to add PS g. Join CA in 4x1 A to u o. '

 4 CA high to add PS g. Join the 4x1 A CA 40L o. '.

 The role of 24 small collection of each million G ess each O content.

 The content of O in 24 cells of R8 3 cells stimulated by PS was higher than normal. However, the low and high CA inhibited the release of PS early O. The inhibition rate was 84.8% <0.01 and 86.8% <0.01 2 5 O content was close to the normal level.

 2 CA 8383 cells PS stimulation release O shadow group C/A o / o " suppression /% normal 4.43 0.32

 PS 33.63 0.80

 CA 5.11 0** 84.8

 40 4.43 0.32 86.8 4 The alveolar cells secrete cells in the shadow of the method Cell, her rational product collection method is the same as 3.

Immunosorbent assay ESA for each cell PS stimulation release of resting due to T F and levels.

As shown in Table 3, the R8 3 cells showed a small PS stimulation of 24 hours, and the content of T Fa increased. The low and high CA levels inhibited the inhibition of T Fa release to some extent by 8.67% and 17.2%, respectively. According to 4 Lmo. The inhibitory effect of CA has <0.05 as shown in Table 4 囤7, R8 3 cells PS stimulation 24 small in the upper middle The increase in the content of both low and high CA can inhibit the release inhibition rate of 57.8%. 05 and 73.6%. 01 There is a reconciliation. 3 CA R8383 cell PS release T

 Normal - 7.26 2.20

 PS - 224.03 8.94

 CA 0 204.62 33.90 8.67

 40 85.5 8.53* 7.2 4 CA 8383 cells PSM release - group C/ o /pg 1

 Suppression /% normal 3.71 0.49

 PS - 31.97 3.14

 CA 0 13.5 0.98 57.8

 40 8.43 0.34 73.6

Claims

Requirements 1, or available in various preventive and/or counter-pneumonia or chemotherapeutic compounds

 Where R has 11

 The X of X in the u 11 can be sufficient for S SO S CO C C C or C where R is derived from the oxygen C C6 C C6 oxy amino

 Amino group of C6 or

 And R respectively from halogen C C6 nitro group C C6 C C6 oxycarboxy amino C C6 C C6 vinyl chloride

 Or

 R from amino C C6 amino amino amino

 Amino or

R from amino or. 2. The purpose of Requirement 1 is that it is in the neutral and 0 1 or 2 p respectively equal to 1 X foot OS or R foot Oxycarbonyloxy

 Nitro or vinyl chloride R

 Ethylene or nitro. 3. The purpose of requirement 1 is that it has the following

 1

 Wherein X feet C S, O or CO R are sufficient for C CF B or C R5 for C B or O 4 , and the use of requirement 1 is specifically for the foot 5 1 [35 44 benzo 123 4 phenyl.

5 5. Any use of requirements 1 to 4 is specifically intended to include derivatives or derivatives.

6. The use of requirement 1 is specifically applicable to, including sulfuric acid, acetic acid.

7. The use of claim 1 is characterized by a physical composition comprising an effective amount or a usable and acceptable rest.

8. Any use of requirements 1 to 7 is characterized by the same anti-pneumonia or septic disease including but not, sensitized pneumonia, or radiation pneumonia, infectious diseases, vascular disease, and alveolar alveolar

9. The use of requirement 8 is the same as anti-neoplastic pneumonia.

10. In the use of or with pneumonia or a disease, or

 Containable or usable containers and conditions of use.