CN114206305A - Combination of oligosaccharides and xylitol for skin treatment - Google Patents
Combination of oligosaccharides and xylitol for skin treatment Download PDFInfo
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Abstract
The present invention relates to a topical formulation comprising: at least one prebiotic oligosaccharide selected from fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin and dextran, or combinations thereof; 0.01% to 10% w/w xylitol; and. a pharmaceutically or cosmetically acceptable carrier. The invention also relates to the use of said preparation and to a method for the production thereof.
Description
The present invention relates to a topical formulation comprising a prebiotic oligosaccharide selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or a combination thereof, and xylitol, and its use in therapy by topical administration.
Background
The largest organ of the human body is the skin, which plays a central role in protecting the host from pathogenic infections and penetration of harmful agents. Before birth, the skin is completely sterile, but after birth, environmental microorganisms that are in homeostasis with the host colonize the skin (conize). In addition, after vaginal delivery, excreta and vaginal microorganisms belonging to the microbial flora of the mother also colonize the skin of the infant. The microbial community that survives human skin is called skin microbial community, and it is composed of over 100 different species of bacteria. Skin is the interface of the body with the outside world, and it is the habitat for nonpathogenic commensal microorganisms which play an important role in skin health and disease.
Our skin has approximately 10 aggregates per square centimeter6Bacteria, which constitute our skin microflora. The healthy and balanced skin flora is a microbial barrier against pathogenic microorganisms and it prevents the dry skin conditionCan improve skin health.
Alterations in the skin microbiome are an important component of the pathophysiology of atopic dermatitis. Skin affected by atopic dermatitis is often colonized by staphylococcus aureus, particularly during exacerbation of the disease, while the abundance of other commensal bacteria is significantly reduced. These changes in the skin microbiome negatively affect the epidermal barrier and trigger inflammation. When bacteria such as staphylococcus aureus attach to the skin surface, they form a biofilm that acts as a scaffold for further bacterial growth. Antibiotics are not the best treatment for removing bacteria from the skin of atopic dermatitis patients due to problems such as skin irritation and bacterial resistance.
It is an object of the present invention to provide a topical formulation for the treatment of a skin disease or condition, such as atopic dermatitis.
Disclosure of Invention
In a first aspect, the present invention provides a topical formulation comprising:
prebiotic oligosaccharides selected from fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin and dextran, or combinations thereof;
0.01% to 10% w/w xylitol; and
a pharmaceutically or cosmetically acceptable carrier.
In a second aspect, the invention provides a formulation as defined in accordance with the first aspect of the invention for use in therapy.
In a third aspect, the present invention provides a formulation comprising:
prebiotic oligosaccharides selected from fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin and dextran, or combinations thereof;
xylitol; and
a pharmaceutically or cosmetically acceptable carrier;
the formulation is for treatment by topical administration.
In a fourth aspect, the present invention provides a formulation as defined in accordance with the first aspect of the invention for use as a cosmetic product.
Surprisingly, the applicant has found that a formulation comprising a prebiotic oligosaccharide selected from fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin and dextran, and xylitol has a beneficial effect on the skin microbiome and is therefore suitable for the treatment of skin diseases and conditions and for cosmetic use to improve the appearance of the skin.
In a fifth aspect, the present invention provides a topical formulation comprising a prebiotic oligosaccharide selected from fructooligosaccharide, isomaltooligosaccharide, arabinogalactan, inulin, or dextran, or a combination thereof, for use in the treatment of atopic dermatitis by topical administration.
Other aspects of the invention are more fully described in the following detailed description of various embodiments.
Detailed Description
The present invention provides a topical formulation comprising:
prebiotic oligosaccharides selected from fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin and dextran, or combinations thereof;
0.01% to 10% xylitol; and
a pharmaceutically or cosmetically acceptable carrier.
Oligosaccharides
Oligosaccharides are carbohydrate polymers that contain fewer monosaccharide units than polysaccharides, but more than two or three units in disaccharides or trisaccharides. One exception is lactulose, a disaccharide with properties similar to oligosaccharides and is therefore considered part of oligosaccharides (carbohydrate Polymers 68(2007) 587-.
Galacto-oligosaccharides (GOS), lactulose, polydextrose, inulin and fructo-oligosaccharides (FOS) are oligosaccharides that are recognized as prebiotics. Isomaltooligosaccharides (IMO), arabinogalactans (LAG) and glucans are oligosaccharides recognized as emerging prebiotics (Curr Osteoporos Rep, 2015, 13:363 371). These compounds are indigestible by humans and promote the growth of beneficial microorganisms, which have the ability to improve host health.
The topical formulations of the present invention comprise fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or combinations thereof. For the avoidance of doubt, the terms fructooligosaccharide, isomaltooligosaccharide, arabinogalactan, inulin and dextran include one or more of fructooligosaccharide, isomaltooligosaccharide, arabinogalactan, inulin and dextran, respectively. The invention includes compositions comprising a mixture of one type of oligosaccharide, as well as compositions comprising a mixture of different types of prebiotic oligosaccharides.
Fructooligosaccharides are inulin-type oligosaccharides of D-fructose linked by β - (2 → 1) linkages with terminal D-glucosyl residues (Enzyme micro b. technol., 1996, vol. 19, 8/1). FOS is derived either from hydrolysis of inulin or from sucrose. Sucrose-derived FOS are shorter chain oligomers; typically, three oligosaccharides are produced from sucrose production; 1-kestose, 1-nystose and 1F- β -fructofuranosyl nystose (Annu. Rev. food Sci. technol.2010.1: 305-39).
In one embodiment, the prebiotic oligosaccharide composition of the invention is a blend comprising FOS having a Degree of Polymerization (DP) between 2 and 20. In another embodiment, the prebiotic oligosaccharide is a blend comprising FOS with a DP between 2 and 10 or between 2 and 6. In another embodiment, the prebiotic oligosaccharide of a formulation of the present invention is a blend comprising FOS having a DP of 2 or greater, 4 or greater, 8 or greater, or 10 or greater.
Isomalto-oligosaccharide (IMO) is a glucose oligomer having an alpha-1 → 6-glycosidic linkage. The generic term IMO includes inter alia isomaltose, panose, isomaltotriose, isomaltotetraose, isomaltopentaose, nigerose, kojibiose and some higher branched oligosaccharides. IMO can be industrially produced from starch using an enzymatic process in which starch is first liquefied by alpha-amylase and then hydrolyzed to maltose using beta-amylase. Finally, IMO (Carbohydrate Polymers 68(2007) 587-. Honey, miso, sake and soy sources are all natural sources of IMO.
In one embodiment, the prebiotic oligosaccharide of the present invention is a blend comprising an IMO having a DP between 1 and 20. In another embodiment, the prebiotic oligosaccharide is a blend comprising an IMO having a DP between 2 and 10, or between 2 and 6, or between 1 and 3. In another embodiment, the prebiotic oligosaccharide is a blend comprising IMO having a DP of 6 or greater, or 10 or greater, or 20 or greater.
Arabinogalactans include galactan chains having alternating 5-linked β -D-galactofuranosyl (Galf) and 6-linked β -D-Galf residues, wherein the arabinogalactan chains are attached to the galactan structure at residues 8, 10, and 12. The arabinoglycan chain has three domains; linear 5-bonded α -D-Araf residues, 3, 5-bonded α -D-Araf residues substituted by 5-bonded α -D-Araf at the branching position, and finally the non-reducing end of arabinoglycans consisting of 3, 5-bonded α -D-Araf residues with β -D-Galf- (1-2) - α -D-Araf disaccharide (Bacterial Polysaccharides: current innovations and future threads, 2009). Arabinogalactans are a major component of many gums and occur naturally in plants such as larch.
The DP of arabinogalactans varies depending on the oligosaccharide source. The DP of arabinogalactans derived from white spruce was found to be 100, whereas that derived from douglas fir was found to be 340(Advances in Carbohydrate Chemistry, volume 20, page 432).
Inulin comprises polysaccharides having a backbone of fructose units, which usually carry terminal glucose units. The fructose units are linked by β - (2 → 1) D-fructosyl-fructose linkages and the terminal glucose units are linked by α -D-glucopyranosyl (glucopyranosyl) linkages. Occasionally, inulin does not contain any glucose units. May be represented by the formula GFnAnd FmWherein G is a terminal glucose monomer, F is a fructose unit, and n or m represents the number of fructose monomer units (Journal of Thermal Analysis and calibration, Vol. 71 (2003) 215-224).
Inulin is naturally present in several plants, including the order liliales, i.e. garlic, asparagus, leek and onion, and the family compositae, i.e. jerusalem artichoke and chicory. The chicory is a food grade inulinThe main commercial source (Annu. Rev. food Sci. Technol.2010.1: 305-39). DP varies with the source of inulin, typically from 2 to 10, but in some cases reaches 40 or more (Food Chemistry 113(2009) 1058-. Average DP (DP) of inulin from chicoryav) Is 12, and DP of inulin from artichokeavIs 46. In one embodiment, the prebiotic oligosaccharide composition of the invention is a blend comprising inulin having a DP of 2-20. In another embodiment, the prebiotic oligosaccharide composition comprises inulin with a DP in the range of from 5 to 15 or a DP in the range of from 10 to 15. In another embodiment, the prebiotic oligosaccharide composition is a blend of one or more saccharides having a DP of 10 or greater, 20 or greater, 30 or greater, or 40 or greater.
Dextran is a homopolysaccharide whose backbone comprises alpha- (1,6) -linked d-glucopyranoses. Glucans comprise a family of polysaccharides with different degrees of branching, involving alpha- (1,2), alpha- (1,3) and alpha- (1,4) linkages. Glucans are produced by enzymatic reactions of bacterial origin; the specific bacteria and the type of dextran sucrase that catalyzes the reaction influence the structure of the resulting dextran by influencing the type and degree of branching of the polysaccharide (Carbohydrate Polymers 88(2012) 1440-1444). In one embodiment, the prebiotic oligosaccharide composition of the invention is a blend comprising a glucan having a DP of 2 to 10. In another embodiment, the prebiotic oligosaccharide composition is a blend comprising a glucan having a DP of 2 to 7, or 2 to 5, or 3 to 5.
In one embodiment, the topical formulation comprises a prebiotic agent selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or a combination thereof.
In a preferred embodiment, the prebiotic agent is selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, and inulin.
In another preferred embodiment, the prebiotic agent is selected from the group consisting of arabinogalactans and isomaltooligosaccharides.
In a most preferred embodiment, the prebiotic agent is selected from fructooligosaccharides.
In one embodiment, the topical formulation comprises from 0.01% to 10% w/w of the prebiotic oligosaccharide as defined above, for example from 0.01% to 5% w/w. Alternatively, the formulation comprises 0.1% to 5% w/w, for example 0.5% to 5% w/w, of the prebiotic oligosaccharide.
In a preferred embodiment, the topical formulation comprises 0.01% to 5% w/w of the prebiotic oligosaccharide.
The topical formulation comprises 0.01% to 10% w/w xylitol. Xylitol is a naturally occurring sugar alcohol used as a sweetener. Xylitol is found in low concentrations in the fiber of many fruits and vegetables, and can be extracted from various berries, oats and mushrooms, as well as fibrous materials such as corn husks and sugar cane bagasse.
In one embodiment, the topical formulation comprises 0.01% to 5% w/w xylitol. Alternatively, the formulation comprises 0.1% to 5% w/w xylitol or 0.5% to 5% w/w xylitol.
In a preferred embodiment, the topical formulation comprises from 0.01% to 5% w/w xylitol.
In one embodiment, the topical formulation comprises 0.01% to 8% w/w xylitol. Alternatively, the formulation comprises 0.1% to 7% w/w xylitol or 0.5% to 7% w/w xylitol.
In a preferred embodiment, the topical formulation comprises 1% to 7% w/w xylitol, 3% to 6% w/w xylitol or 4% to 6% w/w xylitol.
In one embodiment, the topical formulation comprises from 10: 1 to 1: 10, from 8: 1 to 1: 8, from 5: 1 to 1: 5 or from 3: 1 to 1:3 of the prebiotic oligosaccharide: xylitol weight ratio.
In a preferred embodiment, the topical formulation comprises 2: 1 to 1: 2 of prebiotic oligosaccharides: xylitol weight ratio.
In a preferred embodiment, the topical formulation comprises 2: 1 to 1: 2 of prebiotic oligosaccharides: xylitol weight ratio.
In another preferred embodiment, the topical formulation comprises a prebiotic oligosaccharide from 1: 1 to 1: 20, from 1: 5 to 1: 15, or from 1: 7 to 1: 12: xylitol weight ratio.
Topical formulations are used in therapy, in particular by topical administration.
In one embodiment, the present invention provides a topical formulation comprising:
at least one prebiotic oligosaccharide selected from fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin and dextran, or combinations thereof;
xylitol; and
a pharmaceutically or cosmetically acceptable carrier;
the topical formulation is used for treatment by topical administration.
In another embodiment, the present invention provides a topical formulation comprising a prebiotic oligosaccharide selected from the group consisting of fructooligosaccharide, isomaltooligosaccharide, arabinogalactan, inulin, and dextran, or combinations thereof, for use in the treatment of atopic dermatitis by topical administration.
In one embodiment, the topical formulation is used to treat a skin disease or condition.
In another embodiment, the present invention provides a topical formulation comprising xylitol for use in therapy, wherein the topical formulation further comprises a prebiotic oligosaccharide selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or a combination thereof.
In another embodiment, the present invention provides a topical formulation comprising xylitol for use in the treatment of a skin disease or condition, wherein the topical formulation further comprises a prebiotic oligosaccharide selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or a combination thereof. In another embodiment, the skin disease or condition is associated with staphylococcus aureus. In yet another embodiment, the skin disease or condition associated with staphylococcus aureus is atopic dermatitis.
In one embodiment, the present invention provides a method of treating a skin disease or condition comprising topically administering to a patient in need thereof an effective amount of a topical formulation according to the present invention.
In another embodiment, the present invention provides the use of a prebiotic oligosaccharide selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or a combination thereof, in combination with xylitol for the manufacture of a medicament for use in a method of treating a skin disease or condition.
In one embodiment, the topical formulation is used to treat a skin disease or condition associated with staphylococcus aureus. A skin disease or condition associated with staphylococcus aureus is one that is caused or promoted by staphylococcus aureus.
Staphylococcus aureus is a gram-positive pathogenic strain that can cause a variety of diseases ranging from clinical inflammation to severe infections causing pneumonia, endocarditis and septicemia. Staphylococcus aureus is one of the most important bacteria in human diseases. Staphylococcus aureus is particularly associated with atopic dermatitis, a common chronic inflammatory skin disease characterized by acute eczematoid erythema of injury. Itching is also prominent and persistent and therefore has an effect on the quality of life. In industrialized countries, atopic dermatitis affects 10-30% of children and 2-3% of adults. Staphylococcus aureus is also a contributing or compounding factor in the pathogenesis of other mild skin infections (such as papules, impetigo, cellulitis, and folliculitis) and more severe invasive diseases (such as pneumonia, vaginitis, meningitis, osteomyelitis, toxic shock syndrome, bacteremia, and sepsis).
In one embodiment, the skin disease or condition is atopic dermatitis (i.e., atopic eczema), particularly atopic dermatitis associated with staphylococcus aureus.
Without being bound by theory, it is believed that the topical formulation of the present invention promotes the growth of staphylococcus epidermidis, the most common isolated bacterial species in healthy skin, which constitutes 90% of the aerobic flora. Staphylococcus epidermidis balances the inflammatory response after skin injury and produces antimicrobial molecules that selectively inhibit skin pathogens. The growth of staphylococcus epidermidis is believed to inhibit the growth of staphylococcus aureus.
The present invention therefore provides the use of a topical formulation according to the invention for preventing the growth of staphylococcus aureus, in particular on the skin of a human or animal.
Also without being bound by theory, it is believed that the topical formulations of the present invention prevent the formation of staphylococcus aureus biofilms, or remove such biofilms once formed (particularly on human or animal skin).
The present invention therefore provides the use of a topical formulation of the invention to prevent the formation of staphylococcus aureus biofilms or to remove such biofilms once formed (particularly on human or animal skin).
In another embodiment, the present invention provides the use of a topical formulation as a cosmetic. In the cosmetic use of the present invention, the topical formulation is not used for treatment. Rather, the formulation is used to improve the appearance of the surface (e.g., skin) to which the formulation is topically applied.
Another aspect of the invention is a method of preparing a topical formulation comprising prebiotic oligosaccharides. In one embodiment, the method comprises mixing the prebiotic oligosaccharide as defined above, xylitol and a pharmaceutically or cosmetically acceptable carrier and then isolating the topical formulation.
Topical formulations are for topical application. The topical formulation may be a skin formulation.
The topical formulation is preferably applied to the skin. Thus, topical formulations are typically in liquid or semisolid form, for example as an emulsion (e.g. an oil-in-water or water-in-oil emulsion), emollient, paste, cream, ointment, gel, shampoo, wipe (wipe), mouthwash (mouthwash), mouthwash (mouthrine) or spray.
Thus, the formulation also includes such pharmaceutically or cosmetically acceptable carriers as are suitable for administration intended for topical administration.
The topical formulation is preferably an oil-in-water emulsion comprising an oil, at least one surfactant-emulsifier, at least one prebiotic oligosaccharide, xylitol and water.
The oil is typically a mineral oil. The emulsion includes other ingredients typically present in oil-in-water emulsions. For example, the formulations of the present invention may optionally contain a moisture protectant, such as glycerin. Such formulations may also contain fatty acid alcohols, such as stearyl alcohol, palmityl alcohol, maleic alcohol or cetyl alcohol. The formulations of the invention also contain an aqueous medium, such as water, which is typically purified.
The fatty acids may have up to 16 to 18 carbons, such as stearates and palmitates, and the like. Optional enhancers such as citrate, maleic acid, ethylenediaminetetraacetic acid, free amino acids and carbomers, xanthan gum, carrageenan and conditioning quaternary polymers may be included.
In addition, it is desirable to include a small amount of a preservative in the formulation of the present invention so that the formulation can be stored in a good state. Preservatives such as methyl and propyl parabens, as well as other known preservatives such as phenoxyethanol, sodium benzoate, and potassium sorbate may be employed. The preparation can also be preserved with pentanediol, decanediol, 1, 2-octanediol, 1, 2-hexanediol, and o-cymene-5-ol.
In addition, it may be desirable to include a surfactant in the formulations of the present invention. The formulation may contain sodium lauryl sulfate (sodium laureth sulfate), sodium myreth sulfate (sodium myreth sulfate), disodium lauryl sulfosuccinate, sodium cocoamphoacetate, and sodium cocoamphoacetate.
The functionality and amounts of other ingredients or excipients will vary depending on the particular formulation of the formulation. For example, body wash, body lotion, emollient, body wash and mouthwash formulations typically contain the following amounts of excipients in addition to the prebiotic oligosaccharide and xylitol.
Shower gel
Components | Amount (% w/w) |
Water (W) | 75-90 |
Surface active agent | 5-10 |
Wetting agent | 0.1-5 |
Conditioning agents | 0.1-5 |
Essence | 0.1-2 |
Skin-moistening agent | 0.1-2 |
Gelling agent | 0.1-2 |
Preservative | 0.1-2 |
Buffering agent | 0.1-2 |
Shampoo compositions
Components | Amount (% w/w) |
Water (W) | 80-95 |
Surface active agent | 5-12 |
Wetting agent | 0.1-5 |
Conditioning agents | 0.1-2 |
Essence | 0.1-2 |
Skin-moistening agent | 0.1-2 |
Antioxidant agent | 0.1-2 |
Antimicrobial agents | 0.1-2 |
Buffering agent | 0.1-2 |
Chelating agents | 0.01-0.5 |
Skin lotion
Components | Amount (% w/w) |
Water (W) | 55-70 |
Skin-moistening agent | 5-20 |
Conditioning agents | 5-10 |
Wetting agent | 0.1-10 |
Surface active agent | 0.1-3 |
Essence | 0.1-2 |
Antioxidant agent | 0.1-2 |
Stabilizer | 0.1-5 |
Viscosity control agent | 0.1-2 |
Gelling agent | 0.1-2 |
Emulsifier | 0.1-2 |
Absorbent agent | 0.1-2 |
Buffering agent | 0.01-0.5 |
Skin-moistening agent
Components | Amount (% w/w) |
Water (W) | 50-70 |
Skin-moistening agent | 5-15 |
Wetting agent | 5-15 |
Conditioning agents | 5-15 |
Emulsifier | 1-10 |
Stabilizer | 0.1-5 |
Antioxidant agent | 0.1-2 |
Gelling agent | 0.1-2 |
Chelating agents | 0.1-2 |
Masking agent | 0.1-2 |
Buffering agent | 0.01-0.5 |
Mouthwash
Components | Amount (% w/w) |
Water (W) | Balance of |
Antiplaque agents | 0.01 to 0.1 percent |
Masking agent | 0.01-0.1 |
Wetting agent | 1-10 |
Taste enhancer | 0.01-1 |
Emulsifier | 0.1-10 |
Wetting agent | 1-20 |
Buffering agent | 0.1-1 |
Stabilizer | 0.1-1 |
The formulations according to the invention are stable and show good physical and chemical stability over time, even at temperatures above ambient temperature.
In another embodiment, the topical formulation is supplied on a wipe. In this embodiment, the user may topically apply the formulation using a wipe.
The following examples describe the successful inhibition of staphylococcus aureus using the formulations of the present invention, thus indicating that topical formulations would be useful in the treatment of skin diseases and conditions, particularly atopic dermatitis.
Examples
Reduction of growth in planktonic and biofilm forms of staphylococcus aureus and staphylococcus epidermidis was investigated using the prebiotic oligosaccharide and xylitol compositions of the invention.
The planktonic form of bacteria is characterized by isolated cells that float independently or exist as a suspension in a liquid medium. The biofilm (or aggregated/sessile) form is characterized by a state in which cells are tightly bound and firmly attached to each other. Typically, biofilm forms are associated with clinical inflammation and infection in humans.
Materials and methods
Fiberaid Lonza (usa) purchased Xylitol (XYL), galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), Isomaltooligosaccharides (IMO), arabinogalactans (LAG), inulin, and dextran. Each prebiotic compound was prepared in phosphate buffered saline (PBS, Thermo Fisher scientific, italy, milan) and stored at-20 ℃. Stock solutions of XYL and GOS (stock solutions) were diluted in PBS to obtain final concentrations of 1%, 2.5%, 5%, and stock solutions of FOS, IMO, LAG, inulin, dextran were diluted in PBS to obtain final concentrations of 1%.
Staphylococcus aureus 815 (clinical strain) and Staphylococcus epidermidis 317 (clinical strain) used in this study were derived from the private collection of the bacteriological Laboratory of the pharmaceutical Department (Bacteriology Laboratory of Pharmacy Department). S. aureus 815 was previously characterized for some biofilm-associated properties (see, e.g., Microb Biotechnol. 2009; 2(6): 634. sup. 641 and J Med. Microbiol. 2007; 56(Pt 4): 519. sup. 523), whereas in this study the hemolytic activity of S.epidermidis 317 was analyzed and the agr allele and the icaA/icaD gene were detected. Briefly, for hemolytic activity, 5. mu.l of tryptone Soy Broth (TSB, Oxoid, Milan, Italy) (OD) of a reconstituted (reconstituted) Staphylococcus epidermidis 317 Broth culture was added6oo0.04-0.05) spot on Trypticase Soy Agar (TSA, Oxoid, Milan, italy) plus 5% sheep sterile blood (Biomerieux) and incubated at 37 ℃ for 48 hours, then cooled at 4 ℃ for 1 hour for evaluation; for agr genotyping, multiplex Polymerase Chain Reaction (PCR) was performed according to Di Stefano et al (Microb Biotechnol. 2009; 2(6):634-641) and the presence of icaA, icaD was detected by PCR according to Zhou et al (BMC infection Dis.2013; 13: 242).
The characterized strains stored at-80 ℃ were grown overnight in TSB (Oxoid, Milan Italy) under aerobic conditions at 37 ℃. After incubation, the broth culture was diluted 1: 10 in the same medium and allowed to recover for 2 hours at 37 ℃ in a thermostated shaking (160 rpm) bath. Finally, the cultures were adjusted in a spectrophotometer (Eppendorf, Milan Italy) to an optical density OD corresponding to 0.5 McLet units6000.12(Int J Mol sci.2013; 14: 13615-. These standardized broth cultures were used for the experiments. Staphylococcus aureus 815 and Staphylococcus epidermidis 317 were characterized for hemolytic activity, agr alleles, icaA/icaD and biofilm formation:
method 1 reduction of plankton growth
The prebiotic oligosaccharides Galactooligosaccharide (GOS), Fructooligosaccharide (FOS), Isomaltooligosaccharide (IMO), arabinogalactan, inulin and dextran were tested in combination with xylitol to evaluate the antibacterial effect against staphylococcus aureus 815 and staphylococcus epidermidis 317 during the planktonic phase. Mu.l of XYL (1%) and 50. mu.l of each standardized broth culture selected from GOS, FOS, IMO, LAG, inulin or dextran (1% each) were inoculated in 96-well plates and incubated aerobically at 37 ℃ for 3h and 24 h. After the time of each test, OD was measured with an ELISA reader (SAFAS, Munich, Germany)600. For the control, the bacterial strains were incubated without the prebiotic formulation. The antibacterial effect of each prebiotic oligosaccharide in combination with XYL was determined as OD relative to control600The percentage of reduction. OD was detected after 3h and 24h600The reduction represents an immediate and effective effect. For three independent experiments, each assay was performed twice (in duplicate).
Method 2-reduction of biofilm formation
Anti-biofilm activity of 1% XYL in combination with 1% GOS, FOS, IMO, LAG, inulin or dextran was also performed on staphylococcus aureus 815 and staphylococcus epidermidis 317 biofilm formation. Briefly, 100 μ l of each prebiotic combination (50 μ l of 1% XYL +50 μ l 1% GOS, FOS, IMO, LAG, inulin or dextran) and 100 μ l of standardized broth culture were inoculated in 96 flat bottom microtiter plates and incubated at 37 ℃ for 3h and 24 h. After incubation, each well of the 96 flat-bottomed microtiter plate was washed twice with sterile PBS, air-dried, stained with 0.1% safranin for 1 minute, and washed with PBS. The stained biofilm was resuspended in 200. mu.l ethanol (95% v/v) and spectrophotometrically at OD using an ELISA reader492Making measurements (e.g., as Nat Prod Res.201630: 1870-1874). For three independent experiments, each assay was performed twice (in duplicate). For the control, the bacterial strains were incubated without the prebiotic formulation. Determining the biofilm formation reducing effect of each prebiotic oligosaccharide in combination with XYL as OD relative to control492The percentage of reduction.
Example 1: combination of various prebiotic oligosaccharides with xylitol in Staphylococcus aureus 815 and the Table relative to the control
Efficacy in reduction of planktonic growth of Staphylococcus epidermidis 317
The percentage of reduction in growth (OD600) of planktonic staphylococcus aureus 815 and staphylococcus epidermidis 317 after 3h, 24h exposure to 1% Xylitol (XYL) and 1% of the preparations GOS, FOS, IMO, LAG, inulin, dextran was as follows:
statistical significance relative to control
Example 2: combination of various prebiotic oligosaccharides with xylitol in Staphylococcus aureus 815 and the Table relative to the control
Efficacy in reduction of Staphylococcus epidermidis 317 biofilm growth
Staphylococcus aureus 815 and Staphylococcus epidermidis 317 biofilm formation (OD) after 3h and 24h treatment with 1% XYL and 1% GOS, FOS, IMO, LAG, inulin, dextran492) The percentage reduction was as follows:
statistical significance relative to control
Example 3: stability of the formulation
Stability studies were performed on three formulations (examples 3.1-3.3).
Each preparation contained fructooligosaccharide (0.5% w/w) and xylitol (5.0% w/w). Each formulation contains additional excipients set forth in the specification, depending on the type of formulation.
The formulations were stored in PET bottles at the temperatures and relative humidities as indicated in the table.
In each case, the formulations were analyzed for appearance, odor, viscosity, pH, and package compatibility (flow rate).
The appearance was evaluated by visual inspection. Odor was evaluated by XX. The viscosity was measured using a brookfield DV2T viscometer (spindle RV05, 10 rpm). The pH of the formulation over time was measured using a seven-easy-melezueler-toledo pH meter. Package compatibility (flow rate) was evaluated by visual inspection.
Example 3.1 atopic day cream
Example 3.2 Mild cleaners
Example 3.3 emollient
Claims (15)
1. A topical formulation, the topical formulation comprising:
at least one prebiotic oligosaccharide selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or combinations thereof;
0.01% to 10% w/w xylitol; and
a pharmaceutically or cosmetically acceptable carrier.
2. The topical formulation of claim 1, wherein the prebiotic oligosaccharide is selected from fructooligosaccharides.
3. The topical formulation of claim 1, wherein the prebiotic oligosaccharide is selected from the group consisting of isomaltooligosaccharides and arabinogalactans or combinations thereof.
4. The topical formulation of any one of claims 1 to 3, wherein the formulation comprises 0.01% to 5% w/w xylitol.
5. The topical formulation of any one of claims 1 to 4, wherein the formulation comprises 0.01% to 10% w/w, for example 0.01% to 5% w/w, of the prebiotic agent.
6. The topical formulation of any one of claims 1 to 5, wherein the formulation comprises a weight ratio of prebiotic agent of from 10: 1 to 1: 10, such as from 2: 1 to 1: 2: xylitol.
7. The topical formulation of any one of claims 1 to 6, wherein the formulation is a solution, an emulsion (e.g., an oil-in-water emulsion or a water-in-oil emulsion), an emollient, a paste, a cream, an ointment, a gel, a mouthwash, or a spray.
8. The topical formulation of any one of claims 1-7, wherein the formulation is an oil-in-water emulsion.
9. A topical formulation according to any one of claims 1 to 8 for use in therapy.
10. A topical formulation for use according to claim 9, which is used in therapy by topical administration.
11. A composition, comprising:
at least one prebiotic oligosaccharide selected from the group consisting of fructooligosaccharides, isomaltooligosaccharides, arabinogalactans, inulin, and dextran, or combinations thereof;
xylitol; and
a pharmaceutically or cosmetically acceptable carrier;
the composition is for treatment by topical administration.
12. A topical formulation for use according to any one of claims 9 to 11, wherein the formulation is for use in the treatment of a dermatological condition.
13. The topical formulation for use according to claim 12, wherein the dermatological disorder is a disease or disorder associated with staphylococcus aureus.
14. The topical preparation for use according to claim 12 or 13, wherein the skin disease or condition is atopic dermatitis.
15. Use of a topical formulation according to any one of claims 1 to 8 as a cosmetic product.
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GB1911071.7 | 2019-08-02 | ||
PCT/EP2020/071769 WO2021023695A1 (en) | 2019-08-02 | 2020-08-03 | Combinations of oligosaccharides and xylitol for dermatological treatment |
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CN108355013A (en) * | 2018-05-23 | 2018-08-03 | 佛山市芊茹化妆品有限公司 | A kind of multi-functional dispel livid ring around eye composition and its application |
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