CN105251011A - Membrane-spraying agent for superficial burns and preparation method thereof - Google Patents
Membrane-spraying agent for superficial burns and preparation method thereof Download PDFInfo
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Abstract
The invention provides a membrane-spraying agent for superficial burns and a preparation method thereof and relates to the field of medical science. The membrane-spraying agent is prepared from, by weight, flamazine, antibacterial agents, epidermal growth factors, topical anaesthetics, borneol, lithospermum extract liquid, radix angelicae extract liquid, golden cypress extract liquid, polygonum cuspidatum extract liquid, membrane-forming agents, glycerinum and the balance water. The preparation method includes the steps that firstly, the topical anaesthetics, the borneol and the epidermal growth factors are dissolved in a water solution of the glycerinum; then, the flamazine, the antibacterial agents and the membrane-forming agents are dissolved in a small amount of water; finally, the mixture is evenly mixed with the lithospermum extract liquid, the radix angelicae extract liquid, the golden cypress extract liquid, the polygonum cuspidatum extract liquid and the balance water, and the membrane-spraying agent is obtained. By means of the membrane-spraying agent, pain can be relieved rapidly, high sterilization and disinfection functions are achieved, and the position of burns can be recovered more rapidly. Compared with traditional ointment, the membrane-spraying agent is convenient to use and suitable for superficial burns.
Description
Technical field
The present invention relates to medicine, particularly a kind of spray-filming agent.
Background technology
Burn is a kind of more common injury, usually betides in daily life, also can betide in contingency, experiment and war.Burn refers generally to heating power, comprise the histologic lesion that hydrothermal solution, steam, high-temperature gas, flame, red-hot metal liquid or solid etc. are caused, main finger skin and/or mucosa, severe patient also can injure subcutaneous or/and sub-mucosal tissues, as muscle, bone, joint even internal organs.To the order of severity of burn, many employings three degree of quarterings judge at present:
I degree (erythematous): only injure epidermis shallow-layer--horny layer, clear layer, granular layer or injure stratum aculeatum, but genetic horizon is still living and in good health.Local is rubescent, micro-swollen, causalgia, without vesicle.Fully recover in 3-5 days, take off fines, do not stay cicatrix.
II degree (vesiculovirus): be divided into Superficial bums and deepⅱdegreeburn.Superficial bums: have larger blister, edema companion severe pain, dermal sensation is irritated.Although Superficial bums injures most skin basal layer, do not injure the nipple structure of skin corium.The intrinsic stem cell of basal layer also there is the basal layer of part health just because of Superficial bums, and basal layer is the position that skin progenitor cell is the most intensive, so constantly can divide, breed after skin Superficial bums.Finally can complete the Regeneration and Repair of injured skin, realize Scarless wound healing, generally need 1 ~ 2 week.Deepⅱdegreeburn is except epidermis, whole papillary layer of corium burn, and reticular layer of corium part is got involved, and the hair follicle and the sweat gland that are positioned at corium deep layer still have vigor.The recovery from illness in 3 ~ 4 weeks of general need, has cicatrix after healing.
III degree (eschar): palor or sallow carbonization, dry, hide-like, dermal sensation is blunt, and pain is not obvious.Wound healing is comparatively slow, and majority needs skin-grafting, leaves cicatrix or/and deformity after healing.
Superficial burns refers generally to the burn of wound surface self-heal in latter 21 days of wound, comprises I degree of burn and light degree Ⅱ and partly more shallow deepⅱdegreeburn.
Burn often brings and compares bitter sorrow experience, and particularly the burn of face can bring heavy psychological burden to patient.Therefore provide a kind of and can alleviate that patient body is painful and the Burn medicine being of value to rehabilitation has very real meaning.
Summary of the invention
For above-mentioned technical problem, the invention provides a kind of spray-filming agent for superficial burns and preparation method thereof.Spray-filming agent for superficial burns of the present invention is made up of the component of following percentage by weight: silver sulfadiazine 0.1 ~ 5%, antibacterial 0.1 ~ 3%, epidermal growth factor 0.01 ~ 0.1%, local anesthetic 0.05 ~ 1%, Borneolum Syntheticum 0.1 ~ 1%, shikonin extract 0.5 ~ 5%, Radix Angelicae Dahuricae extracting solution 1 ~ 8%, cortex phellodendri extract 1 ~ 8%, Rhizoma Polygoni Cuspidati extracting solution 2 ~ 10%, film former 0.1 ~ 5%, glycerol 1 ~ 10%, water surplus.
Further, be made up of the component of following percentage by weight: silver sulfadiazine 0.5 ~ 3%, antibacterial 0.5 ~ 2%, epidermal growth factor 0.03 ~ 0.08%, local anesthetic 0.1 ~ 0.5%, Borneolum Syntheticum 0.3 ~ 0.8%, shikonin extract 3 ~ 5%, Radix Angelicae Dahuricae extracting solution 3 ~ 5%, cortex phellodendri extract 3 ~ 5%, Rhizoma Polygoni Cuspidati extracting solution 4 ~ 8%, film former 0.5 ~ 3%, glycerol 2 ~ 8%, water surplus.
Particularly, be made up of the component of following percentage by weight: silver sulfadiazine 2%, antibacterial 1%, epidermal growth factor 0.05%, local anesthetic 0.3%, Borneolum Syntheticum 0.5%, shikonin extract 2%, Radix Angelicae Dahuricae extracting solution 4%, cortex phellodendri extract 4%, Rhizoma Polygoni Cuspidati extracting solution 6%, film former 1%, glycerol 6%, water surplus.
Particularly, described film former is the carboxymethyl chitosan that deacetylation is greater than 85%.
Particularly, described antibacterial is selected from any one in chlorhexidine acetate, chlorhexidine gluconate, benzalkonium bromide, polyhexamethylene guanidine.Wherein be preferably chlorhexidine gluconate.
Particularly, described local anesthetic is selected from the one in procaine, lignocaine or tetracaine.
The preparation method of the spray-filming agent for superficial burns of the present invention comprises the following steps:
(1). by formula ratio, after the mixing of the water of glycerol and same volume, local anesthetic, Borneolum Syntheticum and epidermal growth factor are dissolved in wherein;
(2). by formula ratio, silver sulfadiazine, antibacterial and film former are dissolved in a small amount of water;
(3). add shikonin extract, Radix Angelicae Dahuricae extracting solution, cortex phellodendri extract, Rhizoma Polygoni Cuspidati extracting solution and excess water, mix homogeneously and get final product by after the solution mixing obtained by step (1) and (2).
Particularly, the preparation method of described shikonin extract, Radix Angelicae Dahuricae extracting solution, cortex phellodendri extract and Rhizoma Polygoni Cuspidati extracting solution is: Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati are cleaned after pulverizing respectively, the ratio of 5g water is added in 1g Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri or Rhizoma Polygoni Cuspidati, respectively Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati are boiled the water to evaporating 2/3 volume, elimination residue, gained solution is Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati extracting solution.
Carboxymethyl chitosan has good water solublity, can suppress the growth and breeding of some funguses, antibacterial and virus.Also there is the effect promoting blood coagulation, can be used as hemorrhage.It also can be used for Wound filling material, has sterilizing, promotes wound healing, absorbs the effects such as Wound exudate, not easily syneresis.
Radix Arnebiae (Radix Lithospermi) (latin name: Arnebiaeradix), bitter in the mouth cold in nature, enters percardium, Liver Channel.There is effect of clearing away heat and cooling blood, promoting blood circulation and detoxication, rash speckle removing.Contain for heat in blood poison, macule purple black, measles without adequate eruption, skin infection, eczema and extreme misery burn.Modern pharmacology research surface, Radix Arnebiae (Radix Lithospermi) is external has inhibitory action to virus and antibacterial, and can accelerate epithelial growth and treatment burn, and topical application can promote wound healing.
The Radix Angelicae Dahuricae (latin name: Angelicaedahuricaeradix): acrid in the mouth, warm in nature, return lung, spleen, stomach warp.There is the cold expelling that induces sweat, wind-expelling pain-stopping, clearing the nasal passage, dampness leukorrhagia stopping, detumescence and apocenosis, effect of dispelling wind for relieving itching.Record in Compendium of Material Medica: the Radix Angelicae Dahuricae is positive bright principal agent, therefore can control disorders of blood, fetal diseases again, and the pain relieving of evacuation of pus granulation promoting.
Cortex Phellodendri (latin name: Phellodendrichinensiscortex): bitter in the mouth, cold in nature, return kidney, urinary bladder channel.Have and have heat clearing and damp drying, pathogenic fire purging removes steams, effect of detoxification sore treatment.
Rhizoma Polygoni Cuspidati (latin name: Polygonicuspidaterhizomeetradix): mildly bitter flavor, cold nature, returns liver, gallbladder, lung meridian.For jaundice due to damp-heat, stranguria with turbid discharge, leukorrhagia, rheumatic arthralgia, carbuncle sore tumefacting virus, burn due to hot liquid or fire, amenorrhea, lump in the abdomen, instep plays damage, cough due to lung-heat.
Spray-filming agent for superficial burns of the present invention is sprayed on burn site surface can form layer protecting film rapidly; Can quickly alleviating pain; Chitosan inherently has antibacterial activity, compound silver sulfadiazine and cationic surfactant, makes the present invention have very strong sterilizing effect to wound; Be aided with Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati etc. have therapeutic effect Chinese medicine to burn; Epidermal growth factor can make burn site recover faster.Compare traditional ointment, spray-filming agent of the present invention is easy to use, is applicable to superficial burns.
In order to understand better and implement, the following detailed description of the present invention.
Detailed description of the invention
preparation embodiment
The preparation method of the spray-filming agent for superficial burns of the present invention comprises the following steps:
(1). Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati are cleaned respectively after pulverizing, the ratio of 5g water is added in 1g Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri or Rhizoma Polygoni Cuspidati, respectively Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati are boiled the water to evaporating 2/3 volume, elimination residue, gained solution is Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati extracting solution.
(2). by table 1 formula ratio, after the mixing of the water of glycerol and same volume, local anesthetic, Borneolum Syntheticum and epidermal growth factor are dissolved in wherein;
(3). by table 1 formula ratio, silver sulfadiazine, antibacterial and film former are dissolved in a small amount of water;
(4). add step (1) obtained shikonin extract, Radix Angelicae Dahuricae extracting solution, cortex phellodendri extract, Rhizoma Polygoni Cuspidati extracting solution and excess water by after the solution mixing obtained by step (2) and (3), mix homogeneously and get final product.
The each component formula amount of < table 1, by weight percentage (%) >
film-formation result embodiment
Test specimen: sample obtained by the embodiment of the present invention 1 ~ 5 and commercially available product (Jin Fusheng)
Three kinds of sprays are sprayed on skin by test method: 5 experimenters participate in double blind experiment, are: the evaluation index of film-formation result with mobility, drying property, film property.Wherein mobility standards of grading are: 1 point-be very easy to run off, 2 points-be easier to flowing, 3 points-seldom flow; Drying property standards of grading are: 1 be divided into >6min drying time, 2 points of drying times are that 3-6min, 3 is divided into <3min drying time; Film property standards of grading are: 1 point-imperceptible obvious film, 2 points-can be formed incomplete film, 3 points-can obviously complete film be formed.Cumulative all marks, and calculate the total score of all experimenters, score value is higher then represents that film-formation result is better.The results are shown in Table 2:
< shows 2>
As can be seen from film-formation result appraisal result, in double blind experiment, the moulding property of the sample of the embodiment of the present invention 1 ~ 5 is good, mobility is little, and its film-formation result is better than commercially available product.
promote wound healing assay embodiment
Test specimen: sample obtained by the embodiment of the present invention 1 ~ 5 and commercially available product (SD-Ag)
Test method: 70 rats, in age in male and female half and half, 6-8 week, is divided into 7 groups at random, often organizes 10.Be divided into embodiment 1 ~ 5 group, commercially available product group and matched group.Abdominal cavity note 10% chloral hydrate 0.7ml, electricity consumption is pushed away and shaves off the hair that back is about 3cm × 3cm size, the region of marking pen labelling 3cm × 2cm is used after spraying 75% ethanol disinfection, back skin of unhairing is cut off with eye scissors, record wound area after dry 1h, each group gives corresponding laboratory sample respectively, and medicinal liquid is from distance 5-10cm spraying (pressing twice), the applied thickness of SD-Ag is 0.2mm, 3 administrations every day; Matched group not administration.Observe the wound situation of rat wound site every day, and 3,5,10,15,20 days after surgery dynamically observe Rat Wound Healing situation, measure wound surface area and calculate healing rate, healing rate=(original area-existing wound surface area)/original area, it is generally acknowledged that traumatic wounds dry tack free is not suppurated, blood crusts comes off naturally, and wound is that fair and tender normal skin shape is considered as healing.The results are shown in Table 3 and table 4:
< table 3 average wound area (mm
2) >
#for with matched group ratio, p < 0.05; * for compared with commercially available product group, p < 0.05.
Average healing rate (%) > of < table 4
#for with matched group ratio, p < 0.05; * for compared with commercially available product group, p < 0.05.
bactericidal assay embodiment
The antibacterial effect of the embodiment of the present invention 1 ~ 5 and SD-Ag is measured according to GB15979-2002 " Disposable Sanitary Accessory sanitary standard " appendix C.
Test organisms: antibacterial: staphylococcus aureus (ATCC6538), escherichia coli (ATCC25922);
Yeast: Candida albicans (ATCC10231).
Bacterium solution preparation: the nutrient agar inclined-plane fresh cultured thing 18 ~ 24h getting bacterial strain 3rd ~ 14 generation, washes lower lawn with 5ml0.03mol/L phosphate buffer (hereinafter referred to as PBS), bacterium is suspended evenly and is diluted to desired concn with above-mentioned PBS.
Operating procedure:
Washed down by test organisms 24h slant culture PBS, make bacteria suspension, the concentration of requirement is: drip on contrast print with 100 μ l, bacterial count recovered is 1 × 10
4~ 9 × 10
4cfu/ sheet.
Get by coupons (2.0cm × 3.0cm) and contrast each 4 of print, be divided into 4 groups and be placed in 4 sterilizing plates.Described contrast print and sample homogeneous material, equal size, but not containing anti-biotic material, and through sterilization treatment.
Get above-mentioned bacteria suspension. dripped 100 μ l each by coupons and contrast print respectively, even spread, start timing, effect 2min, respectively print is thrown people containing 5m1 with aseptic tweezer, corresponding nertralizer in vitro, abundant mixing, do suitably dilution, then wherein 2-3 dilution factor is got, draw 0.5ml respectively, be placed in two plates, pour into cool nutrient agar (antibacterial) to 40-45' DEG C or sabouraud's agar (yeast) 15m1, rotate plate, make it full and uniform, after agar solidification, upset is dull and stereotyped, 35 DEG C of scholars, 2 DEG C of cultivations 48h (antibacterial) or 72h (yeast), do viable bacteria colony counting.Test repetition 3 times, is calculated as follows sterilizing rate: X=(A-B)/A × 100%
In formula: X---sterilizing rate, %;
A---control sample average colony number;
The tested sample average clump count of B---.
Evaluation criterion: sterilizing rate >=90%, product has bactericidal action.Result is as table 5:
< table 5 sterilizing rate, activity is 1:1>
* for compared with SD-Ag, p < 0.05.
analgesic test embodiment (hot plate method in mice)
Healthy kunming mice is selected in experiment, female, body weight 20-23g.Be divided into matched group, Fuatlin Cream group and embodiment group at random.All first survey the threshold of pain (constant temperature water baths of 55 ± 0.5 DEG C) before each mouse experiment, reject the animal that the threshold of pain is less than 5 seconds and is greater than 30 seconds.Embodiment group smears the sample obtained by embodiment 3, and Fuatlin Cream group smears Fuatlin Cream, and matched group does not smear medicine.After 0.5 hour, foot medicine is washed away with ethanol by the toes place coating after two of dosage in table 5.After treating ethanol volatilization, put by mice on 55 ± 0.5 DEG C of constant temperature water bath aluminium sheets, cover with bell glass, record drops into after mice and starts the time of adding oneself metapedes to mice, respectively organize the difference of the threshold of pain before and after administration as the threshold of pain after administration, result through statistical procedures rank rear in table 6:
< table 6. spray-filming agent for superficial burns of the present invention is to analgesic activity (X ± SD) > of hot plate method in mice
#for with matched group ratio, p < 0.05; * for compared with Fuatlin Cream group, p < 0.05.
clinical trial embodiment
In fire victim 196 example of 1 ~ JIUYUE treatment in 2014, man 112 example, female 84 example, 3 years old to 65 years old age, burned part: neck surface 54 example, upper limb 91 example, lower limb 41 example, trunk 10 example.Depth of burn: light degree Ⅱ, burn surface area is less than 10%, without other cohesive disease.Be divided into embodiment group (100 example) and matched group (96 example) at random, two groups of patient ages, sex, burned part, the degree of depth, area, health status compares, and equal P>0.05, has comparability.
Use medicine: the spray-filming agent that embodiment group uses the embodiment of the present invention 3 to prepare, matched group uses Sulfadiazine Silver Cream agent (SD-Ag).
Using method: two form face all uses 0.05% chlorhexidine liquid debridement, remove blister and separated epidermis, the spray-filming agent of embodiment 3 is sprayed on wound surface by embodiment group, drug withdrawal gradually after knot dry crusts, keeps wound surface clean dry.Matched group local is coated with SD-Ag, and disposable coating protects crust, local occur secretions remove in time after coating again, two groups of equal row exposure methods.
Evaluation methodology: observe every day and record wound surface situation and inquiry patient perceptions.1. record two groups of wound pain (point stingless Severe Pain, minimal irritation pain, pain are obvious, but can stand, severe pain resistance to totally 4 grades unbearably) and time of secretions disappearance.2. cure rate: after light degree Ⅱ wound, wound surface disappears (complete epithelization) for curing.Record two groups of average cure times (containing infecting healing person).3. whole body and local excitation symptom, anaphylaxis and other untoward reaction after observation medication.
Statistical method: measurement data t checks, enumeration data χ
2inspection.
Result is as follows: 1. two groups of pain and secretions Disappearance Scenarios compare, and the results are shown in Table 2; 2. two groups of cure rates and healing time compare, and the results are shown in Table 7 and table 8.
< table 7 liang group pain and secretions extinction time >
* represent compared with matched group, p<0.05
< table 8 liang group cure rate and healing time compare >
* represent compared with matched group, p<0.05
Embodiment group only there occurs traumatic infection by 1 example, and incidence rate is 1%, and matched group has 5 examples that traumatic infection occurs, and incidence rate is 5.2%, two groups and does not all find untoward reaction and allergic conditions.
The present invention is not limited to above-mentioned embodiment, if do not depart from the spirit and scope of the present invention to various change of the present invention or distortion, if these are changed and distortion belongs within claim of the present invention and equivalent technologies scope, then the present invention is also intended to comprise these changes and distortion.
Claims (9)
1. the spray-filming agent for superficial burns, it is characterized in that being made up of the component of following percentage by weight: silver sulfadiazine 0.1 ~ 5%, antibacterial 0.1 ~ 3%, epidermal growth factor 0.01 ~ 0.1%, local anesthetic 0.05 ~ 1%, Borneolum Syntheticum 0.1 ~ 1%, shikonin extract 0.5 ~ 5%, Radix Angelicae Dahuricae extracting solution 1 ~ 8%, cortex phellodendri extract 1 ~ 8%, Rhizoma Polygoni Cuspidati extracting solution 2 ~ 10%, film former 0.1 ~ 5%, glycerol 1 ~ 10%, water surplus.
2. the spray-filming agent for superficial burns according to claim 1, it is characterized in that being made up of the component of following percentage by weight: silver sulfadiazine 0.5 ~ 3%, antibacterial 0.5 ~ 2%, epidermal growth factor 0.03 ~ 0.08%, local anesthetic 0.1 ~ 0.5%, Borneolum Syntheticum 0.3 ~ 0.8%, shikonin extract 3 ~ 5%, Radix Angelicae Dahuricae extracting solution 3 ~ 5%, cortex phellodendri extract 3 ~ 5%, Rhizoma Polygoni Cuspidati extracting solution 4 ~ 8%, film former 0.5 ~ 3%, glycerol 2 ~ 8%, water surplus.
3. the spray-filming agent for superficial burns according to claim 2, it is characterized in that being made up of the component of following percentage by weight: silver sulfadiazine 2%, antibacterial 1%, epidermal growth factor 0.05%, local anesthetic 0.3%, Borneolum Syntheticum 0.5%, shikonin extract 2%, Radix Angelicae Dahuricae extracting solution 4%, cortex phellodendri extract 4%, Rhizoma Polygoni Cuspidati extracting solution 6%, film former 1%, glycerol 6%, water surplus.
4. the spray-filming agent for superficial burns according to claims 1 to 3 any one, is characterized in that: described film former is the carboxymethyl chitosan that deacetylation is greater than 85%.
5. the spray-filming agent for superficial burns according to claims 1 to 3 any one, is characterized in that: described antibacterial be selected from chlorhexidine acetate, chlorhexidine gluconate, benzalkonium bromide, polyhexamethylene guanidine any one.
6. the spray-filming agent for superficial burns according to claim 5, is characterized in that: described antibacterial is chlorhexidine gluconate.
7. the spray-filming agent for superficial burns according to claims 1 to 3 any one, is characterized in that: described local anesthetic is selected from the one in procaine, lignocaine or tetracaine.
8. prepare a method for the spray-filming agent for superficial burns described in claims 1 to 3 any one, it is characterized in that comprising the following steps:
(1). by formula ratio, after the mixing of the water of glycerol and same volume, local anesthetic, Borneolum Syntheticum and epidermal growth factor are dissolved in wherein;
(2). by formula ratio, silver sulfadiazine, antibacterial and film former are dissolved in a small amount of water;
(3). add shikonin extract, Radix Angelicae Dahuricae extracting solution, cortex phellodendri extract, Rhizoma Polygoni Cuspidati extracting solution and excess water, mix homogeneously and get final product by after the solution mixing obtained by step (1) and (2).
9. the preparation method of the spray-filming agent for superficial burns according to claim 8, it is characterized in that: the preparation method of described shikonin extract, Radix Angelicae Dahuricae extracting solution, cortex phellodendri extract and Rhizoma Polygoni Cuspidati extracting solution is: Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati are cleaned respectively after pulverizing, the ratio of 5g water is added in 1g Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri or Rhizoma Polygoni Cuspidati, respectively Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati are boiled the water to evaporating 2/3 volume, elimination residue, gained solution is Radix Arnebiae (Radix Lithospermi), the Radix Angelicae Dahuricae, Cortex Phellodendri and Rhizoma Polygoni Cuspidati extracting solution.
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| CN201510782940.5A CN105251011B (en) | 2015-11-13 | 2015-11-13 | A kind of spray-filming agent and preparation method thereof for superficial burns |
| PCT/CN2015/098898 WO2017080048A1 (en) | 2015-11-13 | 2015-12-25 | Film spraying agent for superfical burns and preparation method therefor |
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| CN114533655A (en) * | 2022-02-22 | 2022-05-27 | 中国人民武装警察部队特色医学中心 | Improved sulfadiazine zinc-silver cream and preparation method thereof |
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| CN105251011B (en) | 2018-12-28 |
| WO2017080048A1 (en) | 2017-05-18 |
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