CN106310389A - Bacterial cellulose patch used for gynecology and preparation method thereof - Google Patents
Bacterial cellulose patch used for gynecology and preparation method thereof Download PDFInfo
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- CN106310389A CN106310389A CN201610912544.4A CN201610912544A CN106310389A CN 106310389 A CN106310389 A CN 106310389A CN 201610912544 A CN201610912544 A CN 201610912544A CN 106310389 A CN106310389 A CN 106310389A
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- bacterial cellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
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- General Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
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Abstract
The invention provides a bacterial cellulose patch. The cellulose is formed by threadlike fiber, the degree of polymerization is 2000-20000, the cellulose is of a porous net shape, and the thickness is 0.04-0.09mm. The bacterial cellulose patch is prepared by adopting a freezing and thawing cycling method. Because the bacterial cellulose patch is of a mesh structure, the biological patch material can be used for treating abdomen femoral hernia diseases, and the greatest significance is that the patch can be used for treatment of gynecopathy, thus completely overcoming the defect of easy triggering of a series of complications caused by poor biocompatibility, hard and rough texture, and easy forming of lumps of peripheral tissues due to stimulation of foreign matters for a long time, greatly reducing the risk of infection during application of the patch material to gynecoiatry, and greatly widening the application scope of the cellulose patch.
Description
Technical field
The present invention relates to a kind of cellulose sticking patch and preparation method, particularly to a kind of bacterial fibers that can be used for gynecological's class
Element sticking patch and preparation method.
Background technology
The patching material used when treating female pelvic floor dysfunctional disease (PFD) at present is substantially polypropylene type material
Material (simple polypropylene or PP composite material).This kind of Biocompatibility is poor, and quality is hard coarse, and long-term foreign body stimulates
Easily cause surrounding tissue to tie lump, have impact on physiological function, as vagina tissue hardens, vesical perforation, eating thrown local organization of wearing and tearing
Thus cause a series of complication, become the potential source of infection.In July, 2011, FDA Food and Drug Administration (FDA) for
Use in organ prolapse at the bottom of basin and urinary incontinence are performed the operation.And Bacterial cellulose biology is as a kind of natural biologic material, by
Increasing application for the treatment of disease, but by Chinese patent ZL 201410089918.8 " a kind of Bacterial cellulose biological sticking patch and
Its manufacture method " disclosed in Bacterial cellulose sticking patch due to the limitation of material structure, existing being the most still only used for treats abdomen femoral hernia etc.
Disease, and cannot be used for treating gynaecopathia.
Summary of the invention
It is desirable to provide a kind of cellulose sticking patch and preparation method, this material can be widely used for treating all kinds of of gynecological
Disease and be substantially reduced infection risk.The present invention is realized by below scheme:
A kind of Bacterial cellulose sticking patch, cellulose is by the acetobacter xylinum (Acetobacter in acetobacter
Xylinum) metabolite prepares, and chemical composition is the polymer that glucopyranose monomer is connected with β-Isosorbide-5-Nitrae-glycosidic bond,
Being made up of filamentary fibers, the degree of polymerization is 2000～20000, and crystal formation is I type, and crystallization index is 50～95%, in holey, and hole
Footpath is 1～2mm, and thickness is 0.04～0.09mm.
In order to optimize microstructure further, improve Bacterial cellulose mechanics and physiological property and effect, sticking patch include as
Lower structural behaviour is improved:
Sticking patch is when water content is 50%, and its fracture strength is 30～70Mpa；In I crystal, the ratio of I α kenel is 50
85%；When sticking patch does not absorbs water, the density of dry film is 1.08～2.35g/cm-3。
Thin with disclosed in Chinese patent ZL201410089918.8 of Bacterial cellulose used in the sticking patch of the present invention
Fungin is essentially identical, is all by acetobacter xylinum (the English name Acetobacter xylinum) generation in acetobacter
Thanking to product to prepare, chemical composition is that glucopyranose monomer (β-D-Glucose) is connected and shape by β-Isosorbide-5-Nitrae-glycosidic bond
The one become, without branch, macromole branch polymer, is made up of unique filamentary fibers, and fibre diameter is between 3～4nm, often
One filamentary fibers bandwidth is up to 30～100nm, and purity is up to reaching 99%, without hemicellulose, lignin, pectin and
Other cell wall components.
For preparing above-mentioned cellulose sticking patch, implement according to the following steps:
The first step: by the Bacterial cellulose slurry of lyophilizing, be scattered in the phosphate buffer solution that pH value is 6～7, then to it
Middle addition 2,2,4,4-tetramethyl sends pyridine living free radical polymerization (English abbreviation TEMPO) and alkali metal chlorate's mixing；
Second step: alkali metal hypochlorite is dissolved in the phosphate buffer solution that pH value is 6～7, then is poured into the first step
System solution in, then when being warming up to 50～70 DEG C, after being incubated 1～3 hour, add ethanol and terminate reaction；
3rd step: question response system cooling after, reacted slurry is put into-10 DEG C～-20 DEG C by alkali metal hydrogen-oxygen
In the system of compound, carbamide and water composition, mix system, form clear solution；It is added thereto to cross-linking agent again, after mixing, in
React 1～3 hour at 50 DEG C～-70 DEG C DEG C, obtain bacterial cellulose gel；
4th step: the gel the 3rd step obtained is freezing 24～38 hours under the conditions of-50 DEG C～-40 DEG C, in
25～30 minutes freezing 24～38 hours under the conditions of-50 DEG C～-40 DEG C of standing under conditions of 25～35 DEG C, so
Circulate at least 3 times；Freezing 24～48 hours under the conditions of-50 DEG C～-30 DEG C, prepare the antibacterial in holey fine afterwards
Dimension element sticking patch.
Bacterial cellulose used in 1st step and the Bacterial cellulose disclosed in Chinese patent ZL201410089918.8
Essentially identical, it is all to be prepared by acetobacter xylinum (Acetobacter xylinum) metabolite in acetobacter, chemistry becomes
The one being divided into glucopyranose monomer (β-D-Glucose) to be connected by β-Isosorbide-5-Nitrae-glycosidic bond and to be formed is without branch, big
Molecule branch polymer, is made up of unique filamentary fibers, and fibre diameter is between 3～4nm, and each filamentary fibers bandwidth can
Reach 30～100nm, and purity is up to reaching 99%, without hemicellulose, lignin, pectin and other cell wall components.
For preparing more preferably sticking patch, following optimal conditions can be used:
In 1st step, Bacterial cellulose slurry, 2,2,4,4-tetramethyls send pyridine living free radical polymerization and alkali metal chlorate
Mass ratio is (100～110): (0.06～0.08): (3～4), and the consumption of phosphate buffer is: every 100g Bacterial cellulose slurry
Material adds to 400ml phosphate buffer.
In 2nd step, alkali metal hypochlorite's solution is 1:(50～70 with the volume ratio of phosphate buffer solution).
The mass ratio of three kinds of compounds of system of alkali metal hydroxide, carbamide and water composition in the 3rd step is (7～8):
(12～14): (81～90)；The cross-linking agent used be that functional group comprises epoxy radicals and chloro and C atomic number be 3～6 straight
Alkane, such as epoxychloropropane, epoxy chlorobutane, epoxy chloropentane etc., or the polyprotic acid that carbon number is 4～6, such as maleic
Diacid, fumaric acid, succinic acid etc..
Although cellulose itself is netted in the cellulose patching material disclosed in Chinese patent ZL201410089918.8
Structure, this is netted on microcosmic, and patching material overall structure is solid surface plank frame；And the cellulose of the present invention
The entirety of patching material is then in holey and the thinner thickness structure, also commonly referred to as mesh sheet with certain pore size；To the greatest extent
The cellulose mesh sheet of pipe material of the present invention be holey and thickness the most relatively thin, but strength character is good.The most this have high-strength
The mesh sheet structure of degree so that the biology patching material of the present invention can be not only used for abdomen femoral hernia disease treatment, and the meaning of maximum
Justice is sticking patch can be applied to gynopathic treatment, can overcome completely existing in gynecological use polypropylene based material because of
The stimulation of poor biocompatibility, quality hard foreign body coarse, long-term easily causes surrounding tissue knot lump easily to cause serious complications
Defect, be substantially reduced patching material and be applied to infection risk during gyniatrics, significantly widened the application model of cellulose sticking patch
Enclose.
Figure of description
The surface structure schematic diagram of the cellulose sticking patch of Fig. 1 embodiment 1
Detailed description of the invention
Embodiment 1
Prepare according to the following steps:
1st step: the Bacterial cellulose slurry of 100g lyophilizing, dispersed with stirring is (0.05M, pH in 400ml phosphate buffer solution
Value is about 6.89), then by 0.06g TEMPO, 3gNaClO2Pour in above-mentioned system respectively, stirring mixing；Mixing speed
10000rmp.The cellulose used is by acetobacter xylinum (Acetobacter xylinum) metabolite in acetobacter
Preparing, chemical composition is that glucopyranose monomer (β-D-Glucose) connects, by β-Isosorbide-5-Nitrae-glycosidic bond, formed
Planting without branch, macromole branch polymer, be made up of unique filamentary fibers, fibre diameter is between 3～4nm, each thread
Fiber bandwidth is up to 30～100nm, and purity is up to reaching 99%, without hemicellulose, lignin, pectin with other are thin
Cell wall composition.
2nd step: take 2mlNaClO solution, is dissolved in 100ml phosphate buffer solution (0.05M, pH value is about 6.89), then falls
Enter in the system that the 1st step prepares, stirring mixing, mixing speed 10000rmp, the above-mentioned system of post-heating to 60 DEG C, insulation is 3 little
Shi Hou, closes agitator, adds 10ml ethanol, terminates reaction.
3rd step: treat the 2nd step reaction system cooling, repeatedly clean Bacterial cellulose slurry with deionized water 5 times, with from
Scheming dries slurry, afterwards will centrifugal after Bacterial cellulose slurry put into be pre-chilled to-15 DEG C by NaOH, carbamide and water according to
Mass ratio is in the system of 7:12:81 composition, uses equal pulp grinder to mix system, forms clear solution；Again by the cross-linking agent ring of 2ml
Oxygen chloropropane joins in above-mentioned clear solution, after stirring 15min, reacts 2h and obtain Bacterial cellulose at 60 DEG C under room temperature
Gel.
4th step: put into by gel in-45 DEG C of refrigerators, freezing 24 hours, takes out and puts in 30 DEG C of baking ovens, 30 minutes, followed by
Continuing puts in-45 DEG C of refrigerators, and the slurry after freezing is put in freeze dryer by such cycle-index 3 times, and in-50 DEG C, lyophilizing 30 is little
Time.
Using above step, obtain a kind of Bacterial cellulose sticking patch, its structure is as it is shown in figure 1, in holey, aperture is
2mm, thickness is 0.07mm), wherein cellulose is by acetobacter xylinum (Acetobacter xylinum) metabolism in acetobacter
Product prepares, and chemical composition is the polymer that glucopyranose monomer is connected with β-Isosorbide-5-Nitrae-glycosidic bond, by filamentary fibers group
Become；After testing, the degree of polymerization of cellulose is 2000～20000, and crystal formation is I type, and crystallization index is 50～95%, I α in I crystal
The ratio of kenel is 50 85%；When sticking patch does not absorbs water, the density of dry film is 0.85g/cm31.08～2.35g/cm-3.Sticking patch exists
When water content is 50%, fracture strength is up to 68MPa.
Embodiment 2
Essentially identical with the preparation method of embodiment 1, but use following different condition parameter:
1. by the NaClO in the 1st step2Change KClO into2, and Bacterial cellulose usage of sizing agent be 110g, 2,2,4,4-tetramethyls
Base sends pyridine living free radical polymerization consumption to be 0.08g and KClO2Consumption be 4g.
2. change the NaClO in 2 steps into KClO.
3. the NaOH in the 3rd step is changed into KOH, and the mass ratio of three kinds of compounds of system of KOH, carbamide and water composition is
4:7:45。
Prepare cellulose sticking patch, in cellular, aperture is 1.8mm, thickness be 0.06mm after testing, when sticking patch does not absorbs water
The density of dry film is 1.15g/cm31.08～2.35g/cm3.Sticking patch is when water content is 50%, and fracture strength is up to 65MPa.
Embodiment 3
Essentially identical with the preparation method of embodiment 1, but use following different condition parameter:
1. change the cross-linking agent epoxychloropropane used in the 3rd step into maleic acid polyprotic acid.
2. in the 4th step, the temperature in circulating frozen step is-50 DEG C, 30 hours time；Stand 30 minutes at 25 DEG C, follow
Ring 5 times；Freezing 48 hours under the conditions of-30 DEG C afterwards.
The cellulose sticking patch prepared, in cellular, aperture is 1mm, thickness be 0.09mm after testing, dry when sticking patch does not absorbs water
The density of film is 2.35g/cm-3.Sticking patch is when water content is 50%, and fracture strength is up to 70Mpa.
Claims (10)
1. a Bacterial cellulose sticking patch, cellulose is prepared by the acetobacter xylinum metabolite in acetobacter, chemical composition
The polymer being connected with β-Isosorbide-5-Nitrae-glycosidic bond for glucopyranose monomer, is made up of filamentary fibers, the degree of polymerization be 2000～
20000, crystal formation is I type, and crystallization index is 50～95%, it is characterised in that: in holey, aperture is 1～2mm, and thickness is
0.04～0.09mm.
2. Bacterial cellulose biological sticking patch as claimed in claim 1, it is characterised in that: when water content is 50%, breaking of sticking patch
Resistance to spalling is 30～70Mpa.
3. Bacterial cellulose biological sticking patch as claimed in claim 1 or 2, it is characterised in that: in I crystal, the ratio of I α kenel is 50
～85%.
4. Bacterial cellulose biological sticking patch as claimed in claim 1 or 2, it is characterised in that: the density of dry film when sticking patch does not absorbs water
It is 1.08～2.35g/cm-3。
5. the method for preparation Bacterial cellulose sticking patch as described in one of Claims 1 to 4, it is characterised in that: according to the following steps
Implement,
The first step: by the Bacterial cellulose slurry of lyophilizing, be scattered in the phosphate buffer solution that pH value is 6～7, then add wherein
Enter 2,2,4,4-tetramethyl and send pyridine living free radical polymerization and alkali metal chlorate's mixing；
Second step: alkali metal hypochlorite is dissolved in the phosphate buffer solution that pH value is 6～7, then is poured into the body of the first step
It is in solution, then when being warming up to 50～70 DEG C, after being incubated 1～3 hour, adds ethanol and terminate reaction；
3rd step: question response system cooling after, reacted slurry is put into-10 DEG C～-20 DEG C by alkali metal hydroxide,
In the system of carbamide and water composition, mix system, form clear solution；It is added thereto to cross-linking agent again, after mixing, in 50 DEG C
～react 1～3 hour at-70 DEG C DEG C, obtain bacterial cellulose gel；
4th step: the gel that the 3rd step is obtained under the conditions of-50 DEG C～-40 DEG C freezing 24～38 hours, in 25～
Under conditions of 35 DEG C, 25～30 minutes freezing 24～38 hours under the conditions of-50 DEG C～-40 DEG C of standing, so circulate
At least 3 times；Freezing 24～48 hours under the conditions of-50 DEG C～-30 DEG C, prepare the Bacterial cellulose in holey afterwards
Sticking patch.
The method preparing Bacterial cellulose sticking patch the most as claimed in claim 5, it is characterised in that: in described 1st step, antibacterial is fine
Dimension element slurry, 2,2,4,4-tetramethyl send pyridine living free radical polymerization and alkali metal chlorate's mass ratio for (100～110):
(0.06～0.08): (3～4), the consumption of phosphate buffer is: every 100g Bacterial cellulose slurry adds to 400ml phosphoric acid slow
Rush in liquid.
7. the method preparing Bacterial cellulose sticking patch as described in claim 5 or 6, it is characterised in that: alkali gold in described 2nd step
The volume ratio belonging to hypochlorite solutions and phosphate buffer solution is 1:(50～70).
8. the method preparing Bacterial cellulose sticking patch as described in claim 5 or 6, it is characterised in that: the alkali in described 3rd step
The mass ratio of three kinds of compounds of system of metal hydroxides, carbamide and water composition is (7～8): (12～14): (81～90).
9. the method preparing Bacterial cellulose sticking patch as described in claim 5 or 6, it is characterised in that: the friendship in described 3rd step
Connection agent is that functional group comprises epoxy radicals and chloro and that carbon number is 3～6 linear paraffin, or carbon number is more than 4～6
Unit's acid.
The method preparing Bacterial cellulose sticking patch the most as claimed in claim 9, it is characterised in that: the function in described 3rd step
That group comprises epoxy radicals and chloro and that carbon number is 3～6 linear paraffin is epoxychloropropane.
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| CN201610912544.4A CN106310389A (en) | 2016-10-19 | 2016-10-19 | Bacterial cellulose patch used for gynecology and preparation method thereof |
| CN201710283604.5A CN107115563B (en) | 2016-10-19 | 2017-04-26 | Bacterial cellulose patch for gynecology and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108676099A (en) * | 2018-05-17 | 2018-10-19 | 天津科技大学 | A kind of preparation method of oxidizing bacteria cellulose solution |
| CN110559481A (en) * | 2019-11-04 | 2019-12-13 | 深港产学研基地 | Surgical implant material for mechanical repair of pelvic floor muscles of gynecology |
| CN113952516A (en) * | 2021-09-28 | 2022-01-21 | 北京科技大学 | Polymorphic self-adaptive bio-based endometrium repair material and preparation method thereof |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110585479A (en) | 2019-11-04 | 2019-12-20 | 深港产学研基地 | Surgical implant material for muscle mechanics-assisted repair and preparation method thereof |
| AU2021213023A1 (en) * | 2020-01-31 | 2022-09-15 | Cass Materials Pty Ltd | Treatment of bacterial nanocellulose |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591448B (en) * | 2009-06-22 | 2012-02-15 | 天津科技大学 | Method for preparing bacterial cellulose membrane with high rehydration |
| CN103800942B (en) * | 2012-11-14 | 2015-09-09 | 深圳迈普再生医学科技有限公司 | Pelvic floor patch |
| CN103861146B (en) * | 2014-03-13 | 2016-01-13 | 海南光宇生物科技有限公司 | A kind of bacteria cellulose biological sticking patch and manufacture method thereof |
| CN104587516B (en) * | 2014-12-29 | 2017-06-06 | 深圳先进技术研究院 | A kind of transparent degradable bacteria cellulose regeneration membrane and its preparation method and application |
-
2016
- 2016-10-19 CN CN201610912544.4A patent/CN106310389A/en active Pending
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- 2017-04-26 CN CN201710283604.5A patent/CN107115563B/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108676099A (en) * | 2018-05-17 | 2018-10-19 | 天津科技大学 | A kind of preparation method of oxidizing bacteria cellulose solution |
| CN110559481A (en) * | 2019-11-04 | 2019-12-13 | 深港产学研基地 | Surgical implant material for mechanical repair of pelvic floor muscles of gynecology |
| CN113952516A (en) * | 2021-09-28 | 2022-01-21 | 北京科技大学 | Polymorphic self-adaptive bio-based endometrium repair material and preparation method thereof |
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| CN107115563A (en) | 2017-09-01 |
| CN107115563B (en) | 2020-08-07 |
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Application publication date: 20170111 |