CN103520102A - Vitamin D nano-emulsion and preparation method thereof - Google Patents
Vitamin D nano-emulsion and preparation method thereof Download PDFInfo
- Publication number
- CN103520102A CN103520102A CN201310479192.4A CN201310479192A CN103520102A CN 103520102 A CN103520102 A CN 103520102A CN 201310479192 A CN201310479192 A CN 201310479192A CN 103520102 A CN103520102 A CN 103520102A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- nano
- emulsion
- water
- tween
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a vitamin D nano-emulsion and a preparation method thereof. The vitamin D nano-emulsion comprises vitamin D and tween-80 in a mass ratio of 1:(1-6), and water of which the mass is 0.8-4.5 times of the total mass of vitamin D and tween-80. The method comprises the following steps: adding vitamin D and tween-80 into a container, uniformly mixing, and adding water to obtain a mixed solution; performing ultrasonic treatment on the mixed solution until the mixed solution is clear and transparent to obtain the vitamin D nano-emulsion. The method is used for preparing the vitamin D nano-emulsion by adopting an ultrasonic emulsification method, is simple in production process, mild in condition, short in preparation time and low in equipment requirement. The prepared vitamin D nano-emulsion is of an oil-in-water mode, is clear and transparent, good in water solution and good in stability, has a grain distribution range of 28-66nm and average grain diameter of 41nm, and accords with the basic characteristics of a nano-grade material.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of vitamin D nano-emulsion and preparation method thereof.
Background technology
Vitamin D is one of nutrient of needed by human, and it,, regulating the metabolism of calcium, phosphorus, promotes bone growth, regulates Growth of Cells differentiation and the aspects such as adjusting of immunologic function are had to biological activity widely.But easily photodissociation of vitamin D itself, oxidation, to thermally labile, and water insoluble, therefore greatly limited its range of application.Prior art is mainly to utilize gelatin, white sugar and starch parcel vitamin D, adopts fluid bed drying process to produce and does not belong to microcapsule technology, and its product dispersibility, emulsion stability in water is poor, and embedding rate is not high, and bag oil mass can only reach 10% left and right.
Nano-emulsion (NDnoemulsion, NE) claims again microemulsion (Microemulsion, ME), is a kind of transparent or semitransparent thermodynamic stable system being mixed to form with proper proportion by oil phase, water, surfactant and cosurfactant.Nano-emulsion preparation can improve the dissolubility of insoluble drug, strengthens the stability of labile drug, and viscosity is low, particle diameter is little, be uniformly dispersed, and can promote medicine absorption in vivo, improves its bioavailability.At present, the nanocrystallization technology of medicine has become one of focus of novel pharmaceutical formulation research.
Summary of the invention
The object of the present invention is to provide a kind of vitamin D nano-emulsion and preparation method thereof, this preparation method production technology is simple, and the vitamin D nano-emulsion making can improve water solublity and the stability of vitamin D.
For achieving the above object, the technical solution used in the present invention is:
A nano-emulsion, comprises that mass ratio is 1:(1～6) vitamin D and tween 80, and quality is the water of 0.8～4.5 times of vitamin D and tween 80 gross mass.
It is oil-in-water type vitamin D nano-emulsion.
Its particle size distribution range is 28～66nm, and mean diameter is 41nm.
A preparation method for vitamin D nano-emulsion, comprises the following steps:
1) in container, add vitamin D and tween 80, stirring and evenly mixing, as oil phase, wherein the mass ratio of vitamin D and tween 80 is 1:(1～6);
2) water is added in the container that is contained with oil phase, obtain mixed solution, wherein the addition of water is 0.8～4.5 times of oil phase quality, and mixed solution is carried out to supersound process, until mixed solution clarification is bright, obtains vitamin D nano-emulsion.
Described water is deionized water or distilled water.
The omnidistance time of described supersound process is 15～400s.
3s intermittently during every ultrasonic 3-5s during described supersound process, the omnidistance time is the summation of ultrasonic time and intermittent time.
The power of described supersound process is 0.1～75KW, and frequency is 20KHz～500MHz.
The temperature of described supersound process is 5～65 ℃.
Further, the vitamin D nano-emulsion of preparing need keep in Dark Place.
With respect to prior art, the present invention has following beneficial effect:
The present invention adopts ultrasonic emulsification method to prepare vitamin D nano-emulsion, and employing vitamin D is raw material, and vitamin D is mixed homogeneously by a certain percentage with surfactant tween 80 and water, then carries out supersound process and obtains vitamin D nano-emulsion.Production technology of the present invention is simple, mild condition, preparation time is short, equipment requirements is low, and adopts vitamin D nano-emulsion that method of the present invention makes also to improve water solublity and the stability of vitamin D.
Vitamin D nano-emulsion provided by the invention is bright for being uniformly dispersed, clarifying, water solublity is good, has good vitamin D stability and water solublity.
Further, vitamin D nano-emulsion provided by the invention is oil-in-water type, and its particle size distribution range is 28～66nm, and mean diameter is 41nm.
Accompanying drawing explanation
Fig. 1 is the particle size distribution figure of the vitamin D nano-emulsion prepared of the present invention.
The specific embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment 1:
A nano-emulsion, comprise that mass ratio is vitamin D and the tween 80 of 1:1, and quality is the deionized water of 0.8 times of vitamin D and tween 80 gross mass.
Its preparation method comprises the following steps:
1) for 1:1, in beaker, add vitamin D and tween 80 in mass ratio, stir, as oil phase;
2) by quality, be that the deionized water of 0.8 times of oil phase quality is added in the beaker that fills oil phase, obtain mixed solution, mixed solution is carried out to supersound process, 3s intermittently during every ultrasonic 3s during supersound process, the omnidistance time of supersound process be the omnidistance time of 15s(be total ultrasonic time and total intermittent time and), temperature during supersound process is 65 ℃, power is 75KW, frequency is 20KHz, until mixed solution clarification is bright, obtain vitamin D nano-emulsion, vitamin D nano-emulsion is kept in Dark Place.
Embodiment 2:
A nano-emulsion, comprise that mass ratio is vitamin D and the tween 80 of 1:6, and quality is the deionized water of 4.5 times of vitamin D and tween 80 gross mass.
Its preparation method comprises the following steps:
1) for 1:6, in beaker, add vitamin D and tween 80 in mass ratio, stir, as oil phase;
2) by quality, be that the deionized water of 4.5 times of oil phase quality is added in the beaker that fills oil phase, obtain mixed solution, mixed solution is carried out to supersound process, 3s intermittently during every ultrasonic 3s during supersound process, the omnidistance time of supersound process be the omnidistance time of 400s(be total ultrasonic time and total intermittent time and), temperature during supersound process is 40 ℃, power is 0.1KW, frequency is 200KHz, until mixed solution clarification is bright, obtain vitamin D nano-emulsion, vitamin D nano-emulsion is kept in Dark Place.
Embodiment 3:
A nano-emulsion, comprise that mass ratio is vitamin D and the tween 80 of 1:3, and quality is the deionized water of 3 times of vitamin D and tween 80 gross mass.
Its preparation method comprises the following steps:
1) for 1:3, in beaker, add vitamin D and tween 80 in mass ratio, stir, as oil phase;
2) by quality, be that the deionized water of 3 times of oil phase quality is added in the beaker that fills oil phase, obtain mixed solution, mixed solution is carried out to supersound process, 3s intermittently during every ultrasonic 4s during supersound process, the omnidistance time of supersound process be the omnidistance time of 200s(be total ultrasonic time and total intermittent time and), temperature during supersound process is 15 ℃, power is 10KW, and frequency is 25MHz, until mixed solution clarification is bright, obtain vitamin D nano-emulsion, vitamin D nano-emulsion is kept in Dark Place.
Embodiment 4:
A nano-emulsion, comprise that mass ratio is vitamin D and the tween 80 of 1:2, and quality is the deionized water of 3 times of vitamin D and tween 80 gross mass.
Its preparation method comprises the following steps:
1) for 1:2, in beaker, add vitamin D and tween 80 in mass ratio, stir, as oil phase;
2) by quality, be that the deionized water of 3 times of oil phase quality is added in the beaker that fills oil phase, obtain mixed solution, mixed solution is carried out to supersound process, 3s intermittently during every ultrasonic 4s during supersound process, the omnidistance time of supersound process be the omnidistance time of 80s(be total ultrasonic time and total intermittent time and), temperature during supersound process is 5 ℃, power is 20KW, and frequency is 150MHz, until mixed solution clarification is bright, obtain vitamin D nano-emulsion, vitamin D nano-emulsion is kept in Dark Place.
Embodiment 5:
A nano-emulsion, comprise that mass ratio is vitamin D and the tween 80 of 1:4, and quality is the deionized water of 3.5 times of vitamin D and tween 80 gross mass.
Its preparation method comprises the following steps:
1) for 1:4, in beaker, add vitamin D and tween 80 in mass ratio, stir, as oil phase;
2) by quality, be that the deionized water of 3.5 times of oil phase quality is added in the beaker that fills oil phase, obtain mixed solution, mixed solution is carried out to supersound process, 3s intermittently during every ultrasonic 5s during supersound process, the omnidistance time of supersound process be the omnidistance time of 20s(be total ultrasonic time and total intermittent time and), temperature during supersound process is 8 ℃, power is 50KW, frequency is 500MHz, until mixed solution clarification is bright, obtain vitamin D nano-emulsion, vitamin D nano-emulsion is kept in Dark Place.
Embodiment 6:
A nano-emulsion, comprise that mass ratio is vitamin D and the tween 80 of 1:5, and quality is the deionized water of 4 times of vitamin D and tween 80 gross mass.
Its preparation method comprises the following steps:
1) for 1:5, in beaker, add vitamin D and tween 80 in mass ratio, stir, as oil phase;
2) by quality, be that the deionized water of 4 times of oil phase quality is added in the beaker that fills oil phase, obtain mixed solution, mixed solution is carried out to supersound process, 3s intermittently during every ultrasonic 5s during supersound process, the omnidistance time of supersound process be the omnidistance time of 30s(be total ultrasonic time and total intermittent time and), temperature during supersound process is 35 ℃, power is 0.2KW, frequency is 500KHz, until mixed solution clarification is bright, obtain vitamin D nano-emulsion, vitamin D nano-emulsion is kept in Dark Place.
Fig. 1 is the particle size distribution figure of the vitamin D nano-emulsion prepared of the present invention, as can be seen from the figure little, the narrow diameter distribution of its particle diameter, and particle size distribution range is 28～66nm, mean diameter is 41nm.
Water solublity and the stability of the vitamin D nano-emulsion of below being prepared by the present invention are investigated.
1. vitamin D nano-emulsion water solublity is investigated
The vitamin D nano-emulsion of preparing through this method can be soluble in water rapidly, and solution clarification is bright, without muddy thing, illustrates that vitamin D nano-emulsion water solublity is good.
2. vitamin D nano-emulsion study on the stability
2.1 physical stabilities are investigated
2.1.1 centrefuge experiment
According to two appendix requirements of Pharmacopoeia of the People's Republic of China version in 2000, the centrifugal 15min of 4000r/min should not observe lamination, and the vitamin D nano-emulsion of being prepared by this method through test does not have lamination, and stability meets the requirements.
2.1.2 jolting test
Respectively get 10mL vitamin D nano-emulsion, fill nitrogen, be sealed in 25mL test tube, in 25 ℃ of water bath with thermostatic control agitators, 100rpm jolting, respectively in 12h, 24h, 48h, 72h sampling, measures the centrifugal stability parameter Ke of vitamin D nano-emulsion under each sample time.The results are shown in Table 1.
The stability parameter of table 1 vitamin D nano-emulsion under the different jolting time
Test shows, jolting on the Ke value impact of vitamin D nano-emulsion not quite continuously.
2.1.2 hot test
Vitamin D nano-emulsion fills nitrogen, sealing, respectively at placing 10 days under the condition of 40 ℃, 60 ℃, 70 ℃, investigates particle diameter and the distribution of vitamin D nano-emulsion respectively at 0 day, 5 days and 10 days.Result of the test is in Table 2.
The impact of table 2 different temperatures on vitamin D nano-emulsion particle diameter
Test shows, under different temperatures, vitamin D nano-emulsion particle diameter is without significant change, but long-time storage should be avoided high temperature.
2.1.3 accelerated test
Accelerated test can be carried out under 30 ℃ of conditions.Vitamin D nano-emulsion is placed 6 months under 30 ℃ of conditions, investigates 0 month, vitamin D nano-emulsion physical property when January, February, March, June.Result of the test is in Table 3.
The impact of table 3 accelerated test on vitamin D nano-emulsion particle diameter
Test shows, under accelerated test condition, vitamin D nano-emulsion particle diameter is without significant change.
2.2 chemical stabilities are investigated
2.2.1 hot test
Vitamin D nano-emulsion fills nitrogen, sealing, respectively at placing 10 days under the condition of 40 ℃, 60 ℃, 70 ℃, investigates the changes of contents of vitamin D nano-emulsion Chinese medicine respectively at 0 day, 5 days and 10 days.Result of the test is in Table 4.
The content of vitamin D nano-emulsion under table 4 different temperatures time conditions
Result of the test shows, vitamin D nano-emulsion is placed under above-mentioned experimental condition, the content of vitamin D within the storage life without significant change.
2.2.2 accelerated test
Vitamin D nano-emulsion is placed 6 months under 30 ℃ of conditions, investigates 0 month, vitamin D content when January, February, March, June changes.Result of the test is in Table 5.
Medicament contg in 6 months vitamin D nano-emulsions of table 5 accelerated test
Above-mentioned test all shows, the physical and chemical index of vitamin D nano-emulsion is without significant change, and vitamin D nano-emulsion has good stability.
Vitamin D is a kind of fatsoluble vitamin, it is made to oil-in-water type nano-emulsion by nanocrystallization technology, not only can reach and make the rapidly-soluble object of vitamin D, improve the stability of vitamin D, and can improve the dissolubility of vitamin D in water, be convenient to control consumption, be convenient to use flexibly in food industry and animal husbandry production.The present invention adopts ultrasonic emulsification method to prepare vitamin D nano-emulsion, production technology is simple, and that the vitamin D nano-emulsion of producing is uniformly dispersed, clarifies is bright, water solublity is good, and particle size distribution range is 28～66nm, mean diameter is 41nm, has reached the requirement of nanometer materials.
Claims (9)
1. a vitamin D nano-emulsion, is characterized in that: comprise that mass ratio is 1:(1～6) vitamin D and tween 80, and quality is the water of 0.8～4.5 times of vitamin D and tween 80 gross mass.
2. vitamin D nano-emulsion according to claim 1, is characterized in that: it is oil-in-water type vitamin D nano-emulsion.
3. vitamin D nano-emulsion according to claim 1 and 2, is characterized in that: its particle size distribution range is 28～66nm, and mean diameter is 41nm.
4. a preparation method for vitamin D nano-emulsion, is characterized in that, comprises the following steps:
1) in container, add vitamin D and tween 80, stirring and evenly mixing, as oil phase, wherein the mass ratio of vitamin D and tween 80 is 1:(1～6);
2) water is added in the container that is contained with oil phase, obtain mixed solution, wherein the addition of water is 0.8～4.5 times of oil phase quality, and mixed solution is carried out to supersound process, until mixed solution clarification is bright, obtains vitamin D nano-emulsion.
5. vitamin D nano-emulsion preparation method according to claim 4, is characterized in that: described water is deionized water or distilled water.
6. the preparation method of vitamin D nano-emulsion according to claim 4, is characterized in that: the omnidistance time of described supersound process is 15～400s.
7. the preparation method of vitamin D nano-emulsion according to claim 6, is characterized in that: 3s intermittently during every ultrasonic 3-5s during described supersound process, the omnidistance time is the summation of ultrasonic time and intermittent time.
8. according to the preparation method of the vitamin D nano-emulsion described in any one in claim 4-7, it is characterized in that: the power of described supersound process is 0.1～75KW, frequency is 20KHz～500MHz.
9. according to the preparation method of the vitamin D nano-emulsion described in any one in claim 4-7, it is characterized in that: the temperature of described supersound process is 5～65 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310479192.4A CN103520102A (en) | 2013-10-14 | 2013-10-14 | Vitamin D nano-emulsion and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310479192.4A CN103520102A (en) | 2013-10-14 | 2013-10-14 | Vitamin D nano-emulsion and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103520102A true CN103520102A (en) | 2014-01-22 |
Family
ID=49922694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310479192.4A Pending CN103520102A (en) | 2013-10-14 | 2013-10-14 | Vitamin D nano-emulsion and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103520102A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104686812A (en) * | 2014-11-18 | 2015-06-10 | 陕西金冠牧业有限公司 | Preparation method of nano vitamin D3 for coating of feed |
| CN105746730A (en) * | 2016-02-22 | 2016-07-13 | 李宏 | Nano-emulsion containing vitamin D and linseed oil as well as preparation method and application of nano-emulsion |
| CN110507610A (en) * | 2019-07-24 | 2019-11-29 | 西北农林科技大学 | A kind of nanoemulsion medicine and preparation method thereof containing vitamin D |
| WO2020253709A1 (en) * | 2019-06-17 | 2020-12-24 | 宁波海奇合昇环能科技有限公司 | Method for preparing transparent water dispersion of fat-soluble nutritional medicine |
| CN114452259A (en) * | 2021-07-28 | 2022-05-10 | 安徽旺盛添加剂有限公司 | Vitamin D micro-capsule calcium tablet and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101637449A (en) * | 2009-08-25 | 2010-02-03 | 曹金党 | Nanometer vitamin self-microemulsion and preparation method thereof |
| WO2010016686A2 (en) * | 2008-08-06 | 2010-02-11 | 주식회사 에델프라우 | Nanoemulsion for local administration |
| CN101797259A (en) * | 2010-03-15 | 2010-08-11 | 河南农业大学 | Compound vitamin nanoemulsion |
| CN102512442A (en) * | 2011-12-15 | 2012-06-27 | 齐鲁动物保健品有限公司 | Zinc chelate-containing compound vitamin oral nano-emulsion and preparation method for same |
| CN102754738A (en) * | 2012-07-27 | 2012-10-31 | 陕西金冠牧业有限公司 | Nano vitamin D3 for producing feed and preparation method thereof |
-
2013
- 2013-10-14 CN CN201310479192.4A patent/CN103520102A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010016686A2 (en) * | 2008-08-06 | 2010-02-11 | 주식회사 에델프라우 | Nanoemulsion for local administration |
| CN101637449A (en) * | 2009-08-25 | 2010-02-03 | 曹金党 | Nanometer vitamin self-microemulsion and preparation method thereof |
| CN101797259A (en) * | 2010-03-15 | 2010-08-11 | 河南农业大学 | Compound vitamin nanoemulsion |
| CN102512442A (en) * | 2011-12-15 | 2012-06-27 | 齐鲁动物保健品有限公司 | Zinc chelate-containing compound vitamin oral nano-emulsion and preparation method for same |
| CN102512442B (en) * | 2011-12-15 | 2013-03-20 | 齐鲁动物保健品有限公司 | Zinc chelate-containing compound vitamin oral nano-emulsion and preparation method for same |
| CN102754738A (en) * | 2012-07-27 | 2012-10-31 | 陕西金冠牧业有限公司 | Nano vitamin D3 for producing feed and preparation method thereof |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104686812A (en) * | 2014-11-18 | 2015-06-10 | 陕西金冠牧业有限公司 | Preparation method of nano vitamin D3 for coating of feed |
| CN104686812B (en) * | 2014-11-18 | 2020-01-03 | 陕西金冠牧业有限公司 | Coated nano vitamin D for feed3Preparation method of (1) |
| CN105746730A (en) * | 2016-02-22 | 2016-07-13 | 李宏 | Nano-emulsion containing vitamin D and linseed oil as well as preparation method and application of nano-emulsion |
| WO2020253709A1 (en) * | 2019-06-17 | 2020-12-24 | 宁波海奇合昇环能科技有限公司 | Method for preparing transparent water dispersion of fat-soluble nutritional medicine |
| CN110507610A (en) * | 2019-07-24 | 2019-11-29 | 西北农林科技大学 | A kind of nanoemulsion medicine and preparation method thereof containing vitamin D |
| CN114452259A (en) * | 2021-07-28 | 2022-05-10 | 安徽旺盛添加剂有限公司 | Vitamin D micro-capsule calcium tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103520102A (en) | Vitamin D nano-emulsion and preparation method thereof | |
| CN103948035B (en) | A kind of preparation method of peony seed oil microcapsule | |
| CN106579327A (en) | High internal phase gel-like zein Pickering emulsion and preparation method thereof | |
| CN104585835A (en) | Nutrient substance adding method, nutrient particles and food and beverage which contain nutrient particles | |
| CN101244037A (en) | High concentration middle/long fatty milk injection for injection and preparing method thereof | |
| CN105495272A (en) | Preparation method of oil-soluble water-soluble type rosemary antioxidant | |
| CN108064976A (en) | A kind of method that polysaccharide emulsion gel is prepared using Pickering lotions | |
| CN103520103B (en) | A kind of vitamin E nano-emulsion and preparation method thereof | |
| CN104304797B (en) | A kind of manufacturing process of livestock and poultry B B-complex nano-emulsion | |
| CN104073463A (en) | Serum-free protein-free culture medium supporting CHO (Chinese Hamster Ovary Cell) high density suspension culture | |
| CN111096370A (en) | Peony seed oil non-dairy creamer and preparation method thereof | |
| CN103819696A (en) | Preparation method of surface-wrinkled gelatin/hyaluronic acid composite microspheres | |
| CN102641311B (en) | Kiwi fruit seed oil liposome oral liquid and preparation method thereof | |
| CN103520101B (en) | A kind of vitamin A nano-emulsion and preparation method thereof | |
| CN101319200B (en) | Non-serum medium suitable for microencapsulation CHO cell and uses thereof | |
| CN102342523A (en) | Preparation method for selenized carrageenan water-in-oil emulsion, and product and application of selenized carrageenan water-in-oil emulsion | |
| CN102228239B (en) | Construction method of nutrient carrying system based on nano-food | |
| CN105267945A (en) | Calcium tablet for children and pregnant women | |
| CN101181632B (en) | Method for preparing superoxide dismutase microcapsule | |
| CN102919669B (en) | Method for preparing immobilization probiotics by taking grain powder as embedding material | |
| CN106072667A (en) | A kind of silkworm chrysalis polypeptide health-preserving paste | |
| Wang et al. | Optimization of conditions for calcium lactate nano-particle production by chemical precipitation | |
| WO2017199008A1 (en) | Emulsion | |
| CN103735607A (en) | Novel injection composition for packaging fat emulsion and amino acid (17) glucose (11 percent) | |
| CN108938542A (en) | A kind of caviar essence and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C05 | Deemed withdrawal (patent law before 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140122 |