CN104523704A - Pharmaceutical composition for treating liver cancer - Google Patents
Pharmaceutical composition for treating liver cancer Download PDFInfo
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- CN104523704A CN104523704A CN201410628715.1A CN201410628715A CN104523704A CN 104523704 A CN104523704 A CN 104523704A CN 201410628715 A CN201410628715 A CN 201410628715A CN 104523704 A CN104523704 A CN 104523704A
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- General Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a pharmaceutical composition for treating liver cancer, which is prepared by proportionally mixing crude drugs including peimine, curcumol, Hemslecin A and justicidin A. The pharmaceutical composition can be prepared in various forms according to conventional preparation technologies. The pharmaceutical composition provided by the invention is of great significance in preparation of drugs for treating liver cancer.
Description
Technical field
The invention belongs to biomedicine field, relate to a kind of pharmaceutical composition of Hepatoma therapy.
Background technology
According in February, 2010 Ministry of Public Health statistics, annual global number of cancer deaths reaches 1,000 ten thousand.The reason of current global 1/4th human mortalities is caused by cancer, and prediction is gone down by current trend development, is owing to having suffered from cancer to the year two thousand fifty by there being the died of 1/2nd.The pernicious cancer morbidity of China, with annual 2.5-5% speed increment, has become the arch-criminal of serious harm human life.Higher with sickness rate such as hepatocarcinoma in the middle of various types of cancer.
Hepatocarcinoma refers to the malignant tumor betiding liver, comprises primary hepatocarcinoma and secondary liver cancer two kinds, and mostly what the hepatocarcinoma of the daily theory of people referred to is primary hepatocarcinoma.Primary hepatocarcinoma is one of modal malignant tumor clinically, and according to recent statistics, liver cancer patient about 600,000 is newly sent out in the whole world every year, occupies the 5th of malignant tumor.Primary hepatocarcinoma can be divided into Hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed carcinoma of liver by cell typing.Nodular type, massive type and diffuse type can be divided into by the form of tumor.Primary hepatocarcinoma belongs to high morbidity in China, and general male is more than women.China is hepatitis B big country, and the hepatocarcinoma of China is many to be developed on the basis of hbv-liver cirrhosis, and hepatitis C patient is also increasing gradually, also can develop into hepatocarcinoma after hepatitis B.Current China number of the infected accounts for the more than half of the whole world, and account for 55% of global hepatocarcinoma patient, become a large killer of serious threat our people health and lives, its danger can not look down upon.Hepatocarcinoma can betide any age, but is many with 31 ~ 50 years old, and the ratio of men and women is about 8:1.More than 90% belong to when making a definite diagnosis in, late period, surgical engine can many miss, so adopt modern comprehensive treatment to be often subject to a definite limitation because of Radiotherapy chemotherapy and immunization therapy; And Radiotherapy chemotherapy is very big to the treatment toxicity of primary disease, indication then reduces, and curative effect is also poor; Though interventional therapy has certain curative effect, need quite high condition and equipment, spend also larger.Therefore Chinese medicine one of essential therapeutic arsenals becoming primary disease.Chinese medicine also with Radiotherapy chemotherapy fit applications, preferably " attenuation synergistic " effect can be played.
The cause of disease of the treatment by Chinese herbs hepatocarcinoma of hepatocarcinoma, doctor trained in Western medicine thinks mainly relevant with chronic hepatic diseases, aflatoxin, parasite, excessive drinking, inherited genetic factors.In China, the factor maximum with onset of liver cancer rate relation is hepatitis B virus, particularly HBsAg positive.Therefore, HBsAg positive and patients with chronic liver are listed in the high-risk group of hepatocarcinoma.Have research to think, HBsAg has directly carcinogenic possibility, and is not necessarily by this interstage of chronic hepatopathy.
The traditional Chinese medical science thinks that primary disease loses primarily of internal organs asthenia of qi and blood, insufficiency of the spleen wet poly-, the expectorant blood coagulation stasis of blood; The evil poison invasion of six climate exopathogens, evil solidifying poison knot, internal injury caused by excess of seven emotions, depressed emotion etc., can make gas, blood, wet, heat, the stasis of blood, poison tie mutually and form hepatocarcinoma.Primary disease disease located in liver, closely related with spleen, gallbladder, stomach, main pathogenesis is weakened body resistance in interior, and evil poison pents up.In treatment, by determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs, main point of following four types: the treatment by Chinese herbs depression of liver-QI of hepatocarcinoma, square medicine selects bupleurum powder for relieving liver-qi to add and subtract; Qi depression to blood stasis, selects Fuyuan Huoxue Tangization to cut out; Damp and hot poly-poison, Herba Artemisiae Scopariae Decoction is added and subtracted; Deficiency and exhaustion of liver-YIN, square medicine is selected YIGUANJIAN to close xijiao Dihuang Tangization and is cut out.
Peimine (peimine): CAS 23496-41-5, molecular formula C
27h
45nO
3, molecular weight 431.65.
Curcumenol (curcumol): CAS 4871-97-0, molecular formula C
15h
24o
2, molecular weight 236.35.
Hemsleyadin first (Hemslecin A): CAS 58546-34-2, molecular formula: C
32h
50o
8, molecular weight 562.73.There is antibacterial, refrigeration function.
Justicidin A(justicidin A): CAS 25001-57-4, molecular formula C
22h
18o
7, molecular weight 394.38.
4 kinds of medicines structures of pharmaceutical composition of the present invention are as follows:
Peimine (peimine) curcumenol (curcumol)
Hemsleyadin first (Hemslecin A) justicidin A(justicidin A).
Summary of the invention
The object of the invention is the deficiency overcoming background technology, a kind of pharmaceutical composition of Hepatoma therapy is provided.
The present invention is achieved through the following technical solutions:
Composition and the weight portion of the crude drug of the pharmaceutical composition of a kind of Hepatoma therapy of the present invention are:
Peimine 11-33 weight portion curcumenol 16-28 weight portion hemsleyadin first 10-25 weight portion justicidin A30-40 weight portion.
The pharmaceutical composition of a kind of Hepatoma therapy of the present invention can adopt the conventional method of galenic pharmacy to be prepared into tablet, capsule, drop pill.
The pharmaceutical composition of a kind of Hepatoma therapy of the present invention, is characterized in that being used for the treatment of hepatocarcinoma.
Pharmaceutical composition group of the present invention tumor mass reduction compared with model group, medication two weeks each treatment group tumor tissue P53 express and significantly decline; Macrophage CD
68testing result is shown: pharmaceutical composition group of the present invention compares with model control group, has extremely significant difference (P<0.01).
Detailed description of the invention
Below by specific experiment example and embodiment, a kind of pharmaceutical composition for the treatment of gastric cancer of the present invention is described further, but is not limited to the present invention.
Embodiment 1: the pharmaceutical composition of Hepatoma therapy
The composition of the crude drug of the pharmaceutical composition of Hepatoma therapy and weight portion are:
Peimine 11 weight portion curcumenol 28 weight portion hemsleyadin first 10 weight portion justicidin A40 weight portion.
Embodiment 2: the pharmaceutical composition of Hepatoma therapy
The composition of the crude drug of the pharmaceutical composition of Hepatoma therapy and weight portion are:
Peimine 33 weight portion curcumenol 16 weight portion hemsleyadin first 25 weight portion justicidin A30 weight portion.
Embodiment 3: the pharmaceutical composition of Hepatoma therapy
The composition of the crude drug of the pharmaceutical composition of Hepatoma therapy and weight portion are:
Peimine 22 weight portion curcumenol 20 weight portion hemsleyadin first 17 weight portion justicidin A35 weight portion.
Embodiment 4: the pharmaceutical composition of Hepatoma therapy
The composition of the crude drug of the pharmaceutical composition of Hepatoma therapy and weight portion are:
Peimine 28 weight portion curcumenol 20 weight portion hemsleyadin first 15 weight portion justicidin A32 weight portion.
Embodiment 5: the preparation of tablet
Example 1 compositions 150g, adds starch 75g, mixing, granulates, dry, adds microcrystalline Cellulose 20g, magnesium stearate 2.5g, and mixing, is pressed into 1000, obtains present composition tablet.
Embodiment 6: the preparation of capsule
Example 2 compositions 165g, adds starch 65g, mixing, granulates, and dry, granulate, adds appropriate magnesium stearate, and mixing, obtains present composition capsule by encapsulated 1000.
Embodiment 7: the preparation of drop pill
Taking polyethylene glycol 6000 200g water-bath (80 DEG C) heating boils molten, add embodiment 3 compositions 50g, stirring, is coolant with liquid paraffin, puts in glass tubing (4*80cm), chilling temperature is 10 DEG C, drip internal-and external diameter is 7.0/2.0 (mm/mm), and drip is 2cm apart from liquid level, drips speed with per minute 50 for optimum condition, blot the condensing agent on drop pill surface with cotton, obtain present composition drop pill.
Experimental example 1: pharmaceutical composition antihepatocarcinoma effect is tested
1.1 material
The healthy ICR mice 70 of laboratory animal, male, body weight 20 scholar 2 g (Xi'an Jiaotong University Medical College's Experimental Animal Center provides), 28 ~ 30d.Credit number: SCXK (Shan) 2011-001.
Experiment tumor strain: mouse liver cell carcinoma strain (H
22) provided by The Fourth Military Medical University's university animal experimental center.
Medicine: the embodiment of the present invention 1 pharmaceutical composition, embodiment 2 pharmaceutical composition, embodiment 3 pharmaceutical composition, embodiment 4 pharmaceutical composition, lot number is respectively: 20110203,20110204,20110205,20110206.Tegafur Tablet (FT-207), Shanghai Hua Lian pharmaceutical factory of Pharmaceutical Group company limited, the accurate word of traditional Chinese medicines: H31021668 lot number: 110905.
Main agents: P53 protein B A0133 multi-resistance, immunohistochemical staining test kit, Wuhan doctor's moral Bioisystech Co., Ltd provides.Rabbit anti-mouse macrophage polyclonal antibody (SnataCurz, USA); CD
68immunohistochemical staining test kit, Wuhan doctor's moral Bioisystech Co., Ltd provides.Bioactivation element sheep anti-mouse igg BA0523,
DAB developer, immunohistochemical kit, all purchased from Wuhan Boster Biological Technology Co., Ltd.; 0.02% trypan blue, PBS liquid 0.01m citric acid salt buffer, 95% ethanol, formaldehyde, dimethylbenzene, hydrogen peroxide, pure water provide by Shandong College of Traditional Chinese Medicine's Pathological Staff Room.
Major experimental instrument: superclean bench (Suzhou Decontamination Equipment Plant), cycle type histotome (2135 type Germany), optical microscope (Chongqing optical instrument factory), electronic balance (Shanghai second analytical tool factory), horizontal centrifuge (LD-42 type, Beijing Medical Centrifugal Machine Factory), electro-heating standing-temperature cultivator (Shanghai Medical Apparatus and Instruments Factory, HH Bll42), cryogenic refrigerator one (refrigerator factory of Haier, Qingdao), microscope slide, coverslip (the raw instrument of the sub-honorization in Shanghai), true color Pathologic image analysis system (Xiamen company of Mike Audi), CCD photographing unit, Jiangsu Jetta morphological analysis software (EJDASOID), microwave oven one (LG Electrical Appliances Co., Ltd), centrifuge tube, wet box etc.
1.2 experimental technique
The making of animal model: randomly draw 10 mices and do outside Normal group, make for all the other 40 and touch, the strain of rat liver cancer H hepatocarcinoma tumor tumor, extracts tumor liquid under aseptic condition, centrifugal (1500r/min × 2min), adjustment cell concentration is to every milliliter of many 2 × 10m of suspension
2oncocyte, then use 0.25mL syringe with 0.2mL/ only, the right armpit subcutaneous vaccination of mice, it is 100% that the success rate of touching is made in this experiment.Experiment is divided into groups and administration: after modeling, 24h is except normal blank matched group, and mice is divided into 4 groups at random, divides into groups to start gastric infusion the same day, the equal successive administration 14d of each group: Normal group: with normal saline 0.2mL//d; Model control group: with normal saline 0.2mL//d; Ftorafur group: give 0.2mL//d; The aqueous solution that the Tegafur Tablet of 10 times of (containing ftorafur 4.0 mg/mL) quantities of being grown up is made; Embodiment 1 pharmaceutical composition, embodiment 2 pharmaceutical composition, embodiment 3 pharmaceutical composition, embodiment 4 pharmaceutical composition, equal gavage, 0.2mL/, 1 time/d.
2 experimental results
2.1 tumor-inhibiting actions are in table 1.
Table 1 H
22the impact of liver cancer mouse tumor weight and tumour inhibiting rate
| Group | n | Average tumor heavy (g) | Average tumour inhibiting rate % |
| Normal group | 10 | - | - |
| Model control group | 10 | 2.7548 | 0 |
| Ftorafur group | 10 | 1.2568 | 54.38 |
| Embodiment 1 pharmaceutical composition | 10 | 1.3062 | 52.58 |
| Embodiment 2 pharmaceutical composition | 10 | 1.2889 | 53.21 |
| Embodiment 3 pharmaceutical composition | 10 | 1.6066 | 41.68 |
| Embodiment 4 pharmaceutical composition | 10 | 1.5876 | 42.37 |
2.2 saltant type
p53 and macrophage CD
68mensuration in table 2.
The expression of table 2 mutated P53 gene
| Group | n | Saltant type P53 |
| Normal group | 10 | 0.2045 scholar 0.0131 |
| Model control group | 10 | 0.5125 scholar 0.1078 ◇ |
| Ftorafur group | 10 | 0.3267 scholar 0.1732 ▲ |
| Embodiment 1 pharmaceutical composition | 10 | 0.2870 scholar 0.1024 ▲ |
| Embodiment 2 pharmaceutical composition | 10 | 0.3524 scholar 0.0466 ▲ |
| Embodiment 3 pharmaceutical composition | 10 | 0.3372 scholar 0.1122 ▲ |
| Embodiment 4 pharmaceutical composition | 10 | 0.3413 scholar 0.1236 ▲ |
Note: compare with model control group
△p<0.05,
▲p<0.01. compare with normal control
◇p<0.01
2.3 CD
68mensuration in table 3.
Table 3 is group liver cancer mouse macrophage CD respectively
68expression
| Group | n | Macrophage CD 68 |
| Normal group | 10 | 0.5825 scholar 0.1867 |
| Model control group | 10 | 0.4534 scholar 0.0687 |
| Ftorafur group | 10 | 0.3789 scholar 0.0417 △ |
| Embodiment 1 pharmaceutical composition | 10 | 0.5518 scholar 0.0713 △◇ |
| Embodiment 2 pharmaceutical composition | 10 | 0.5224 scholar 0.0746 △◇ |
| Embodiment 3 pharmaceutical composition | 10 | 0.4800 scholar 0.0524 ▲ |
| Embodiment 4 pharmaceutical composition | 10 | 0.5316 scholar 0.0658 △◇ |
Note: compare with model control group
△p<0.05,
▲p<0.01. compare with normal control
◇p<0.01
This experiment Immunohistochemical Method detects H
22the expression of hepatoma carcinoma cell mutant P 53 protein can react the situation of P53 gene mutation.Result display model group mouse mutant P53 Overexpression, is significantly higher than ftorafur positive controls and pharmaceutical composition group of the present invention, illustrates that pharmaceutical composition of the present invention can the expression of mutation inhibiting type P53 gene.Pharmaceutical composition of the present invention can make the expression of apoptosis suppressor saltant type P53 obviously reduce, show pharmaceutical composition energy direct killing oncocyte of the present invention, inhibition tumor cell is bred, liver cancer apoptosis reducing, its mechanism of action may be expressed with suppressor gene p53 to be increased, the expression of hepatocarcinoma apoptosis suppressor saltant type P53 can be reduced, promote that apoptotic generation is relevant.
Pharmaceutical composition group of the present invention compares with ftorafur group, and both tumour inhibiting rates are that the former is not so good as the latter, but the former has shown certain effective tumour inhibiting rate; Pharmaceutical composition of the present invention not only has certain tumor-inhibiting action and antineoplastic invasion and transferance, and can significantly improve the phagocytic function of macrophage.
Claims (7)
1. a pharmaceutical composition for Hepatoma therapy, is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Peimine 11-33 weight portion curcumenol 16-28 weight portion hemsleyadin first 10-25 weight portion justicidin A30-40 weight portion.
2. according to claim 1: a kind of pharmaceutical composition of Hepatoma therapy, it is characterized in that composition and the weight portion of the crude drug making this pharmaceutical composition are:
Peimine 11 weight portion curcumenol 28 weight portion hemsleyadin first 10 weight portion justicidin A40 weight portion.
3. according to claim 1: a kind of pharmaceutical composition of Hepatoma therapy, it is characterized in that composition and the weight portion of the crude drug making this pharmaceutical composition are:
Peimine 33 weight portion curcumenol 16 weight portion hemsleyadin first 25 weight portion justicidin A30 weight portion.
4. according to claim 1: a kind of pharmaceutical composition of Hepatoma therapy, it is characterized in that composition and the weight portion of the crude drug making this pharmaceutical composition are:
Peimine 22 weight portion curcumenol 20 weight portion hemsleyadin first 17 weight portion justicidin A35 weight portion.
5. according to claim 1: a kind of pharmaceutical composition of Hepatoma therapy, it is characterized in that composition and the weight portion of the crude drug making this pharmaceutical composition are:
Peimine 28 weight portion curcumenol 20 weight portion hemsleyadin first 15 weight portion justicidin A32 weight portion.
6. the pharmaceutical composition of a kind of Hepatoma therapy according to claim 1, can adopt the conventional method of galenic pharmacy to be prepared into tablet, capsule, drop pill.
7. the pharmaceutical composition of a kind of Hepatoma therapy according to claim 1, is characterized in that being used for the treatment of hepatocarcinoma.
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|---|---|---|---|
| CN201410628715.1A CN104523704A (en) | 2014-11-11 | 2014-11-11 | Pharmaceutical composition for treating liver cancer |
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|---|---|---|---|
| CN201410628715.1A CN104523704A (en) | 2014-11-11 | 2014-11-11 | Pharmaceutical composition for treating liver cancer |
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|---|---|
| CN104523704A true CN104523704A (en) | 2015-04-22 |
Family
ID=52839463
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|---|---|---|---|
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Citations (6)
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|---|---|---|---|---|
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| CN101074255A (en) * | 2006-05-19 | 2007-11-21 | 樊献俄 | Preparation of hemsleyadine-A and its use of preparing pharmaceutics against cancers |
| CN101352445A (en) * | 2008-08-22 | 2009-01-28 | 中国科学院化学研究所 | Novel use of chuanbeinone compounds |
| CN101422466A (en) * | 2006-05-19 | 2009-05-06 | 樊献俄 | Use of cucurbitacin in preparing medicine for treating cancer |
| CN101569606A (en) * | 2009-06-09 | 2009-11-04 | 沈阳药科大学 | Curcumol liposome and preparation method thereof |
| CN102000072A (en) * | 2009-09-01 | 2011-04-06 | 奇复康药物研发(苏州)有限公司 | Anti-tumor natural medicine coupled with nitric oxide donor and medical use thereof |
-
2014
- 2014-11-11 CN CN201410628715.1A patent/CN104523704A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101032481A (en) * | 2006-03-07 | 2007-09-12 | 杨美华 | Application of traditional Chinese medicine justicia lignanoids part as antineoplastic medicine |
| CN101074255A (en) * | 2006-05-19 | 2007-11-21 | 樊献俄 | Preparation of hemsleyadine-A and its use of preparing pharmaceutics against cancers |
| CN101422466A (en) * | 2006-05-19 | 2009-05-06 | 樊献俄 | Use of cucurbitacin in preparing medicine for treating cancer |
| CN101352445A (en) * | 2008-08-22 | 2009-01-28 | 中国科学院化学研究所 | Novel use of chuanbeinone compounds |
| CN101569606A (en) * | 2009-06-09 | 2009-11-04 | 沈阳药科大学 | Curcumol liposome and preparation method thereof |
| CN102000072A (en) * | 2009-09-01 | 2011-04-06 | 奇复康药物研发(苏州)有限公司 | Anti-tumor natural medicine coupled with nitric oxide donor and medical use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 廖子君 等: "《肿瘤转移学》", 28 February 2007 * |
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Application publication date: 20150422 |