CN112672728A - Topical composition comprising saccharide isomerate for microbiome balance - Google Patents
Topical composition comprising saccharide isomerate for microbiome balance Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Abstract
The present invention relates to topical compositions comprising saccharide isomers for use as prebiotics when applied to the surface of the human body.
Description
Technical Field
The present invention relates to topical compositions comprising saccharide isomers for use as prebiotics.
Background
People often seek to care for themselves and their body surfaces, such as the skin, scalp including hair, armpits, and oral cavity, in the hope of enjoying a healthy lifestyle. Some of the benefits that one desires to obtain include skin health without infection, even skin tone, adequate moisturization, and protection from the ultraviolet rays contained in the sun.
The skin is the outermost protective layer of the organism and is the largest organ of the body. It acts as a barrier and protects the body from external elements. For example, the skin prevents harmful or potentially harmful microorganisms (e.g., bacteria, fungi, and viruses) from entering the body, thereby preventing infection and/or other adverse effects that may result.
However, the skin, as the outermost protective layer, is easily colonized by and continuously kept in contact with microorganisms (e.g., bacteria, fungi, viruses, archaea (collectively referred to as microbiome)) that may be present on the skin. For example, in humans, the cutaneous microbiome includes bacteria that provide benefits to the host (known as commensal or benign bacteria), such as Staphylococcus epidermidis (Staphylococcus epidermidis); and harmful or potentially harmful bacteria (malignant bacteria), such as Staphylococcus aureus (or s. aureus) and Pseudomonas aeruginosa (or p. aeruginosa). Bacteria such as staphylococcus aureus and pseudomonas aeruginosa are not harmful when present on the skin itself. However, these bacteria can become harmful after entering the human body, for example, by ingestion and through skin cuts. Thus, the skin microbiome contains both benign and malignant bacteria. Disruption of the balance between benign and malignant bacteria is the opportunity for disease initiation. Thus, it is often desirable to achieve and maintain microbiome balance, i.e., to maintain a healthy and infection-free state of a human surface (e.g., skin).
Microbiome balance may be achieved, for example, by reducing malignant bacteria by administering a topical composition comprising one or more antimicrobial compounds. However, most, if not all, of the antimicrobial compounds contained in such topical compositions do not function in a selective manner. In other words, antimicrobial compounds do not act selectively on malignant bacteria, but they also act on benign bacteria. Thus, the use of such topical compositions often results in a loss of benign bacterial populations, which is undesirable.
Certain mechanisms in the human body contribute to microbiome balance. For example, keratinocytes, one of the major cell types that are present in large numbers in human body surfaces (e.g., skin), secrete antimicrobial peptides (natural defense system), which protect the skin from attack by malignant bacteria.
Microbiome balance may also be achieved by using prebiotics that promote the growth of benign bacteria compared to malignant bacteria. Thus, the use of prebiotics results in an enhanced benefit from benign bacteria. Benign bacteria are said to provide benefits to their host by, for example, competing with malignant bacteria for nutrients and by secreting metabolites.
Several prebiotic ingredients are known in the art. WO2017/201296(Dermala Inc.) discloses compositions and methods for treating acne vulgaris and mentions glycerol, maltose, lactose as prebiotic compounds.
The ingredient "saccharide isomerate" is a well known hydrating agent that has been used in the compositions. For example, WO 01/70189(Unilever, 2001), US5858997(Unilever, 1999) and WO 97/47280(Unilever, 1997) relate to skin lightening methods and compositions comprising saccharide isomers. WO 97/30690(Unilever, 1997) discloses skin care compositions comprising 1% saccharide isomerate. US5486352(Unilever, 1996) discloses sunscreen compositions comprising 0.2% saccharide isomers. EP 0545716 (Unilever, 1992) discloses a two-phase transparent-opaque soap bar composition comprising pentavidin (a saccharide isomer commercially available from DSM as a humectant under the trade name PENTAVITIN)
) Wherein it is disclosed as a skin care active.
ZA980040(Elma Mckenzie) discloses cosmetic skin treatment compositions. In a preferred embodiment, ZA980040 discloses cosmetic skin treatment compositions containing 4% saccharide isomerate for use as keratin binding complexes.
WO2017/019612(Mary Kay Inc.) discloses methods and compositions suitable for application to skin and hair comprising hydrolyzed algae extract, saccharide isomers, and a dermatologically acceptable carrier, wherein the compositions or methods are capable of moisturizing and/or improving the appearance and/or condition of skin and/or hair.
WO2015/175536 (biowind Technologies Inc.) provides compositions and methods for improving human health and nutrition. In one aspect, it discloses compositions comprising prebiotics, probiotics comprising a mixture of Lactobacillus (Lactobacillus) and/or Bifidobacterium (Bifidobacterium) microorganisms produced by solid substrate and submerged liquid fermentation, and metagens derived from liquid fermentation media of Lactobacillus and/or Bifidobacterium microorganisms (all collectively referred to as microbial compositions)TM) A mixture of (a). It also mentions prebiotics such as inulin, fructooligosaccharides and glucooligosaccharides. In one of the examples, WO2015175536 describes deep moisturizing creams comprising microbial compositionsTMAnd other components comprising saccharide isomers.
It has now been found that topical compositions comprising saccharide isomers provide microbiome balance when applied to a human body surface. It has also been found that the thus obtained microbiome balance is achieved by the carbohydrate isomers acting as prebiotics, i.e. they preferentially promote the growth of benign bacteria compared to malignant bacteria. The benefits of microbiome balance may be achieved by various mechanisms, and it is not necessary that each substance that provides microbiome balance provide microbiome balance by virtue of the substance acting as a prebiotic. The invention in the present application was obtained by finding that saccharide isomerate appears as prebiotics, which has not been understood to date to the inventors' knowledge.
Disclosure of Invention
In one aspect, the present invention relates to the use of a topical composition comprising saccharide isomers as prebiotics when applied to a human surface.
Detailed Description
Any feature of one aspect of the invention may be used in any other aspect of the invention. The word "comprising" means "including," but not necessarily "consisting of or" consisting of. In other words, the listed steps or options need not be exhaustive. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word "about". Numerical ranges expressed in "x to y" format should be understood to include x and y. When multiple preferred ranges are described in the format of "x to y" for a particular feature, it is understood that all ranges combining the different endpoints are also included. Amounts used herein are expressed as weight percent based on the total weight of the composition and are abbreviated as "wt%" unless otherwise indicated. The use of any and all examples, or exemplary language, such as "for example" provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed.
The phrase "microbiome balance" as used herein preferably refers to maintaining a healthy and infection-free state of a human body surface (e.g., skin, scalp including hair, axilla, and oral cavity). The microbiome balance is achieved by the carbohydrate isomers acting as prebiotics (i.e. preferentially promoting the growth of benign bacteria on human surfaces compared to malignant bacteria).
In a first aspect, the present invention relates to a topical composition comprising saccharide isomerate for use in providing microbiome balance when applied to a human surface.
It has been found that the topical composition comprising saccharide isomers according to the present invention (the composition) provides a microbiome balance.
The balance of the microbiome thus obtained is achieved by the carbohydrate isomers acting as prebiotics. It was found that saccharide isomers preferentially promote the growth of benign bacteria such as staphylococcus epidermidis compared to malignant bacteria such as staphylococcus aureus. Thus, saccharide isomers have also been found to act as prebiotics.
Preferably, the composition comprises saccharide isomers in an amount of 0.001 to 10 wt%, more preferably 0.01 to 8 wt%, even more preferably 0.1 to 7 wt%, still more preferably 0.1 to 5 wt%, and still more preferably 0.1 to 3 wt%.
Saccharide isomers may be tradename
(from DSM), trade name Waterin (from Clariant), trade name 'EPS 3 Powder', 'EPS 4 Powder', 'EPS 5 Powder' and 'EPS 15 Powder' (both from Codif) and trade name 'Hyanify' (from Lipotec s.a.).
Preferably, the composition further comprises other prebiotics selected from the group consisting of polyols, monosaccharides, disaccharides, oligosaccharides, polysaccharides and mixtures thereof.
Examples of polyols that may be used as other prebiotics include glycerol, sugar alcohols (e.g., maltitol, sorbitol, xylitol, erythritol, and isomalt), and mixtures thereof.
Examples of monosaccharides that can be used as other prebiotics include glucose, fructose, galactose and mixtures thereof.
Examples of disaccharides that may be used as other prebiotics include sucrose, maltose, lactose, and mixtures thereof.
Examples of oligosaccharides that may be used as other prebiotics include fructooligosaccharides, glucooligosaccharides, and mixtures thereof.
Examples of polysaccharides that may be used as other prebiotics include inulin.
When present, the amount of other prebiotics present in the composition may preferably be from 0.001 to 10 wt%, more preferably from 0.01 to 8 wt%, even more preferably from 0.1 to 7 wt%, still more preferably from 0.1 to 5 wt%, and still more preferably from 0.1 to 3 wt%.
When other prebiotics may be present in the composition, the ratio thereof to saccharide isomers is preferably from 20:1 to 1:20, more preferably from 10:1 to 1:10, even more preferably from 5:1 to 1:5, still more preferably from 2:1 to 1:2, and still more preferably 1: 1.
The topical composition according to the first aspect provides a microbiome balance when applied on a human surface. Preferably, the human body surface is at least one of skin, scalp including hair, axilla, and oral cavity.
In a second aspect, the present invention relates to the use of a topical composition comprising saccharide isomerate for microbiome balancing when applied to a human surface. Microbiome balance is achieved by using topical compositions comprising saccharide isomerate on human body surfaces. Preferably, the human body surface is at least one of skin, scalp including hair, axilla, and oral cavity. The use according to this aspect may be therapeutic or non-therapeutic. Preferably, the use is non-therapeutic, including cosmetic.
In a third aspect, the present invention relates to the use of a topical composition comprising saccharide isomers as prebiotics. When a topical composition comprising saccharide isomerate is applied to a human surface, it is found to promote the growth of benign bacteria such as staphylococcus epidermidis preferentially over malignant bacteria such as staphylococcus aureus. Preferably, the human body surface is at least one of skin, scalp including hair, axilla, and oral cavity. The use according to this aspect may be therapeutic or non-therapeutic. Preferably, the use is non-therapeutic, including cosmetic.
Since the number of benign bacteria increases after exposure to saccharide isomers, the metabolites secreted by benign bacteria may also increase. Without wishing to be bound by theory, it is believed that these metabolites contribute to the body's natural defense system.
Thus, in a fourth aspect, the present invention relates to the use of a topical composition comprising saccharide isomerate for improving the natural defense system of human surfaces by microbiome balance. Preferably, the human body surface is at least one of skin, scalp including hair, axilla, and oral cavity. The use according to this aspect may be therapeutic or non-therapeutic. Preferably, the use is non-therapeutic, including cosmetic.
Thus, in a fifth aspect, the present invention relates to a method of improving the natural defense system of a human body surface by microbiome balance, the method comprising the step of applying the composition according to the first aspect to the human body surface. Preferably, the human body surface is at least one of skin, scalp including hair, axilla, and oral cavity. The method according to this aspect may be therapeutic or non-therapeutic. Preferably, the method is non-therapeutic, including cosmetic.
Preferably, the composition comprises a cosmetically acceptable base. Examples of ingredients that can be used as cosmetically acceptable bases include water, fatty acids, soaps (fatty acid salts), alcohols, and mixtures thereof.
Preferably, the composition comprises water in an amount of 1 to 99 wt%, more preferably 5 to 90 wt%, even more preferably 35 to 80 wt%, and still more preferably 40 to 75 wt%.
Examples of alcohols useful as cosmetically acceptable bases include straight or branched chain alcohols having preferably from 1 to 16, more preferably from 2 to 10, even more preferably from 3 to 8 carbon atoms. Illustrative examples of alcohols that can be used in the composition include methanol, ethanol, isopropanol, n-propanol, isobutanol, n-butanol, n-pentanol, n-hexanol, and mixtures thereof. Preferably, the alcohol is selected from the group consisting of ethanol, isopropanol, and mixtures thereof.
Preferably, the composition comprises the alcohol in an amount of preferably 0.1 to 80 wt.%, more preferably 0.1 to 65 wt.%, even more preferably 1 to 50 wt.%, and even more preferably 5 to 30 wt.%.
Examples of fatty acids that can be used as cosmetically acceptable bases include fatty acids having from 12 to 20, more preferably from 14 to 18 carbon atoms. Examples of such fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and mixtures thereof. The most preferred fatty acid is stearic acid. The fatty acid may also be a hysteric acid which is essentially (typically about 90-95%) a mixture of stearic and palmitic acid in a ratio of 55:45 to 45: 55.
Preferably, the cosmetically acceptable base comprises 1 to 25 wt%, more preferably 3 to 22 wt%, even more preferably 5 to 20 wt%, and still more preferably 6 to 18 wt% fatty acid.
The soap may be formed in situ by the addition of an alkaline agent (e.g., sodium hydroxide or potassium hydroxide); or may be added externally to the composition. For example, when potassium hydroxide is added to a cosmetically acceptable base comprising stearic acid, potassium stearate so formed is understood to be an in situ formed soap which forms part of the cosmetically acceptable base.
Preferably, the composition comprises from 0.1 to 10 wt%, more preferably from 0.1 to 7 wt%, even more preferably from 0.1 to 3 wt% soap.
The composition is preferably in the form of a rinse-off or leave-on composition, more preferably a leave-on composition.
Leave-on compositions preferably refer to compositions that do not require removal from the human body after application of the composition. When the composition is in the form of a leave-on composition, the composition may be in the form of a deodorant (stick, roll-on or spray), hand sanitizer, skin lotion, skin cream, and body spray.
For example, if the composition is in the form of a skin cream, a vanishing cream base, typically comprising 5-25 wt% fatty acid, 0.1-10 wt% soap and 60-80 wt% water, is preferred as a cosmetically acceptable base. The vanishing cream base gives the skin a highly appreciated matte feel (matt feel).
Furthermore, if the composition is in the form of a deodorant, the composition may preferably comprise a conventional deodorant base as a cosmetically acceptable base. By deodorant is meant a product in stick, bead or propellant media for personal deodorant benefits (e.g. application to the axilla (underarm area)), which may or may not contain an antiperspirant active.
Deodorant compositions can be generally in the form of firm solids, soft solids, gels, creams and liquids, and are applied using an applicator suitable for the physical characteristics of the composition. Deodorant compositions delivered by roll-on usually comprise a liquid carrier. The liquid carrier may be hydrophobic or comprise a mixture of hydrophilic and hydrophobic liquids. They may be in the form of emulsions or microemulsions. The liquid carrier or carrier mixture typically comprises 30 to 95 wt%, and in many cases 40 to 80 wt%. The hydrophobic liquid carrier may typically comprise one or more materials selected from the chemical classes of siloxanes, hydrocarbons, branched aliphatic alcohols, esters and ethers having a melting point of not higher than 25 ℃ and a boiling point of at least 100 ℃. The hydrophilic carrier liquid useful in the compositions herein typically comprises water and/or a monohydric or polyhydric alcohol or water-miscible homolog. The polyol typically comprises ethylene glycol or propylene glycol, or homologues such as diethylene glycol may be used. In addition to this suitability, other carriers and components for the deodorant composition may be added.
Rinse-off compositions preferably refer to compositions (e.g., creams including toothpaste, shampoos, hand-wash compositions, and facial cleansing compositions) that are intended/required to be removed from the body by washing with a solvent (preferably water) upon application of the composition. In the case of a rinse-off composition, the cosmetically acceptable base preferably also comprises a surfactant.
For example, if the composition is in the form of a shampoo, the cosmetically acceptable base preferably comprises, in addition to water, an anionic surfactant, such as an alkyl sulfate and/or an ethoxylated alkyl sulfate surfactant. These anionic surfactants are preferably present in an amount of 1 to 20 wt%, more preferably 2 to 16 wt%, even more preferably 3 to 16 wt%. Preferred alkyl sulfates are C8-18 alkyl sulfates, more preferably C12-18 alkyl sulfates, preferably in the form of salts with solubilizing cations such as sodium, potassium, ammonium or substituted ammonium.
Preferably, the composition further comprises one or more skin lightening agents. These one or more skin lightening agents may be selected from niacinamide, resorcinol, phenylethyl resorcinol, 4-alkyl substituted resorcinols (e.g., 4-ethyl resorcinol and 4-hexyl resorcinol), vitamin B6, vitamin C, vitamin A, glutathione precursors, glatirdine, adapalene, aloe vera extract, ammonium lactate, arbutin, azelaic acid, butyl hydroxy anisole, butyl hydroxy toluene, citrate esters, deoxyarbutin, 1, 3-diphenylpropane derivatives, 2, 5-dihydroxy benzoic acid and its derivatives, 2- (4-acetoxyphenyl) -1, 3-dithiane, 2- (4-hydroxyphenyl) -1, 3-dithiane, ellagic acid, glucopyranosyl-1-ascorbate, and mixtures thereof, Gluconic acid, glycolic acid, green tea extract, 4-hydroxy-5-methyl-3 [2H ] -furanone, 4-hydroxyanisole and its derivatives, 4-hydroxybenzoic acid derivatives, hydroxyoctanoic acid, inositol ascorbate (inositol ascorbate), lactic acid, lemon extract, linoleic acid, magnesium ascorbyl phosphate, 5-octanoylsalicylic acid, salicylic acid, 3, 4, 5-trihydroxybenzyl derivatives, acetylglucosamine, pitera extract, symwhite, calcium pantothenate (patent whitening factor (Melano-block)), seppiwhite, soybean extract (bowman birk inhibitor), 12-hydroxystearic acid and mixtures thereof. When used in the compositions, 12-hydroxystearic acid acts as a skin lightening agent rather than a fatty acid. Preferably, the skin lightening agents useful in the compositions are niacinamide, resorcinol, phenylethyl resorcinol, 4-alkyl substituted resorcinols (e.g., 4-ethyl resorcinol, 4-isopropyl resorcinol, and 4-hexyl resorcinol), vitamin B6, 12-hydroxystearic acid, glutathione precursors, glatiramer, and mixtures thereof.
When incorporated, the skin lightening agent may preferably be added in the composition in an amount of 0.001 to 15 wt%, more preferably 0.01 to 10 wt%, even more preferably 0.1 to 5 wt%, and still more preferably 0.5 to 3 wt%.
Preferably, the composition further comprises a preservative to prevent the growth of potentially harmful microorganisms in the composition. Examples of ingredients that can be used as preservatives in the compositions include alkyl esters of p-hydroxybenzoic acid, hydantoin derivatives, propionate salts, and various quaternary ammonium compounds. More preferably, the ingredients that can be used as preservatives in the compositions are sodium benzoate, iodopropynyl butyl carbamate, methylisothiazolinone, phenoxyethanol, methylparaben, propylparaben, imidazolidinyl urea, sodium dehydroacetate, ethylhexyl glycerol, benzyl alcohol, alkane diols, and mixtures thereof. Alkane diols suitable as preservatives are C ortho-substituted with hydroxy groups6-C12An alkane. Illustrative examples include 1, 2-octanediol (octanediol), 2, 3-octanediol, 1, 2-nonanediol, 1, 2-decanediol, 1, 2-hexanediol, 3, 4-octanediol, mixtures thereof, and the like, with octanediol being generally most preferred.
When present in the composition, the preservative may be added in an amount of preferably 0.001 to 5 wt%, more preferably 0.01 to 3 wt%, and most preferably 0.02 to 2 wt%.
Preferably, the composition further comprises a range of other optional ingredients including antioxidants, binders, biological additives, buffering agents, colorants, astringents, fragrances, opacifiers, conditioning agents, exfoliants, pH adjusters, natural extracts, skin sensates, skin soothing agents, emollients, solvents and skin healing agents.
Preferably, the composition is formulated as a powder, a tablet (flake), an emulsion, a cream, a gel or a mousse. More preferably, the composition is formulated in the form of a cream or lotion, and most preferably in the form of a cream. The composition is preferably leave-on. The packaging for the compositions of the present invention may be a patch, bottle, tube, roller-ball applicator, propellant-driven aerosol device, squeeze container or lidded can.
The invention will now be illustrated by the following non-limiting examples.
Examples
Scheme(s)
Preparation of the culture
Cultures of Staphylococcus epidermidis (ATCC 12228), Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 15442) are designated 108Log colony forming units (cfu)/mL were stored in tryptic Soy Broth (TSB; Difco catalog number 211825) and used in the experiments at the appropriate dilutions as specified below.
Example 1: carbohydrate isomers preferentially promote benign over malignant bacteria (e.g., staphylococcus aureus)
Growth of bacteria (e.g. Staphylococcus epidermidis)
Staphylococcus aureus and Staphylococcus epidermidis were grown in TSB in the presence or absence of 2% saccharide isomerate for 24 hours at 37 ℃. At the end of the incubation, the optical density at 620nm was recorded for all test samples. The growth rates of the bacteria in the presence and absence of the saccharide isomers were found to be as follows:
the data in the above table indicate that the saccharide isomers preferentially support the growth of staphylococcus epidermidis over staphylococcus aureus. Thus, the saccharide isomers act as prebiotics, providing a microbiome balance.
Examples 2A, 2B and 2C: growth inhibition study
Overnight growth plate cultures of Staphylococcus epidermidis were serially diluted to 10 in sterile saline6log cfu/mL. In the absence or presence of 1% saccharide isomer, 100. mu.L of this solution was added to 40mL of TSB and incubated aerobically at 37 ℃ for 24 hours with shaking. At the end of 24 hours, the culture was pelleted by centrifugation at 8000rpm for 2 minutes at room temperature and the fermentation broth (supernatant) was collected. Fermentation broth A (collected from the place where the saccharide isomer did not exist) and fermentation broth B (collected from the place where 1% of the saccharide isomer existed) were subjected to filtration sterilization using a 0.22 μm filter. The pH of the broth was checked and the broth was used for growth inhibition studies. Studies were performed in 96-well plates using the test conditions outlined in examples 2A, 2B, and 2C below.
Example 2A
The following test samples were prepared on 96-well plates and the plates were incubated in a plate reader for 24 hours at 37 ℃.
100. mu.L fermentation broth A + 100. mu.L fresh TSB + 20. mu.L Staphylococcus epidermidis (10. mu.L)6Log cfu/mL); and
100. mu.L fermentation broth B + 100. mu.L fresh TSB + 20. mu.L Staphylococcus epidermidis (10. mu.L)6Log cfu/mL)
The optical density was recorded every 1 hour and is shown in table 2A below:
table 2A: staphylococcus epidermidis fermentation liquor and staphylococcus epidermidis
The data in Table 2A above show that neither fermentation broth A (obtained from Staphylococcus epidermidis in the absence of saccharide isomerate) nor fermentation broth B (obtained from Staphylococcus epidermidis in the presence of 1% saccharide isomerate) inhibited the growth of Staphylococcus epidermidis itself.
Example 2B
Further, the following test samples were prepared on a 96-well plate, and the plate was incubated in a plate reader at 37 ℃ for 24 hours.
100. mu.L fermentation broth A + 100. mu.L fresh TSB + 20. mu.L Staphylococcus aureus (10. mu.L)6Log cfu/mL); and
100. mu.L fermentation broth B + 100. mu.L fresh TSB + 20. mu.L Staphylococcus aureus (10. mu.L)6Log cfu/mL)
The optical density was recorded every 1 hour and is shown in table 2B below:
table 2B: staphylococcus epidermidis fermentation liquor and staphylococcus aureus
The data in table 2B above show that fermentation broth B (from staphylococcus epidermidis in the presence of 1% saccharide isomer) inhibits the growth of staphylococcus aureus compared to fermentation broth a (from staphylococcus epidermidis in the absence of saccharide isomer).
Example 2C
Further, the following test samples were prepared in 96-well plates, and the plates were incubated in a plate reader at 37 ℃ for 24 hours.
100. mu.L fermentation broth A + 100. mu.L fresh TSB + 20. mu.L Pseudomonas aeruginosa (10)6Log cfu/mL); and
100. mu.L fermentation broth B + 100. mu.L fresh TSB + 20. mu.L Pseudomonas aeruginosa (10)6Log cfu/mL)
Table 2C: staphylococcus epidermidis fermentation liquor and pseudomonas aeruginosa
The data in Table 2C above show that broth B (from Staphylococcus epidermidis in the presence of 1% saccharide isomer) inhibits the growth of Pseudomonas aeruginosa as compared to broth A (from Staphylococcus epidermidis in the absence of saccharide isomer).
The data in tables 2A, 2B and 2C together indicate that the fermentation broth of staphylococcus epidermidis obtained after fermentation of the saccharide isomers contains one or more metabolites secreted by staphylococcus epidermidis which inhibit harmful/potentially harmful bacteria (such as staphylococcus aureus and pseudomonas aeruginosa) but not staphylococcus epidermidis (symbiotic bacteria) per se.
Example 3: identification of metabolites produced in Staphylococcus epidermidis fermentation saccharide isomerate
The metabolites produced in the fermentation of saccharide isomers by Staphylococcus epidermidis were identified using gas chromatography.
Briefly, for sample preparation, 5mL of supernatant was placed in a petri dish and dried in an oven at 40 ℃. After drying, the residue was redissolved in a 1N HCl-methanol mixture, then 0.5mL BF3 methanol reagent (methylating agent) was added and heated at 75 ℃ for 2 hours. Methylated organic acids were analyzed using GC-MS with SIM mode. Compounds were identified using spectra obtained from standards and cross-validated using n.i.s.t. library. The retention time and the quantification ions for each compound are listed in the table.
| Name of Compound | Retention time (minutes) | For quantifying ions |
| Lactic acid methyl ester | 9.0 | 104，105，96，89，81，61 |
| Succinic acid methyl ester | 12.5 | 115，114，96，87，81，89 |
Fatty acids as well as organic acid methyl esters were quantified by an external calibration method using pure standards.
The detection method comprises the following steps: gas chromatography (Perkin Elmer Clarus500 with GCMS detector) was used. A polar GC column CP WAX 52CB (30 m. times.0.25 mm. times.0.25 μm) was selected for analysis. The injection port temperature was maintained at 220 ℃. The desorption time was 3 minutes. Programming the temperature of the oven to 40 ℃ as an initial temperature, and keeping the temperature for 2 minutes; and the temperature was raised to 250 c at a rate of 10 c per minute for 10 minutes. GCMS was used to analyze the actives and identify compounds using NIST library matching. The mass source temperature was maintained at 200 ℃ and the sweep range was 40-500 m/z. Helium was used as the carrier gas and the study used a splitless injection mode.
The major metabolite produced in the fermentation of saccharide isomers by Staphylococcus epidermidis was identified as lactic acid.
Example 4: dose-dependent increase in lactic acid production in fermentation of saccharide isomerate
The amounts of saccharide isomers indicated in the table below were incubated for 24 hours at 37 ℃ under aerobic conditions with TSB in the absence or presence. At the end of incubation, the lactic acid content of the test sample was determined using gas chromatography as described above.
| Treatment of | Lactic acid% |
| TSB (control) | 0.11 |
| 0.5% saccharide isomerate | 0.49 |
| 1% saccharide isomerate | 0.58 |
| 2% saccharide isomerate | 0.75 |
The data in the above table show that as the amount of saccharide isomer increases, the amount of lactic acid produced by staphylococcus epidermidis increases.
Example 5: in vivo studies demonstrating lactic acid production following fermentation of saccharide isomerate
In an in vivo study conducted over a 2 day period (5 volunteers), 0.5% and 1% saccharide isomers prepared in water were applied 3 times daily to the volar forearms of the volunteers. Samples taken on the third day from the volar forearm (using isopropanol) were analyzed (using gas chromatography as described above) for fold increase in lactic acid content over baseline (untreated). The results obtained are shown in the following table.
| Treatment of | Mean fold increase of lactic acid | Standard error of |
| 0.5% saccharide isomerate | 0.88 | 0.05 |
| 1% saccharide isomerate | 1.75 | 0.29 |
The above data indicate that the amount of lactic acid detected in vivo is proportionally increased after the saccharide isomerate is applied to the surface of the human body, here the skin. This indicates that the skin microbiome can ferment the saccharide isomers and that lactic acid is produced in the bacteria present in the skin microbiome that ferment the saccharide isomers.
Example 6: hand sanitizer compositions comprising saccharide isomerate
| Composition (I) | Amount (wt%) |
| Ethanol | 62 |
| Isopropanol (I-propanol) | 3 |
| Saccharide isomerate | 1 |
| Micro-ingredients (perfumes and polymers) | 1 |
| Water (W) | To 100 |
Example 7: vanishing cream composition comprising saccharide isomers
| Composition (I) | Amount (wt%) |
| Stearic acid | 17 |
| Stearic acid potassium salt | 3 |
| Polyoxyethylene lauryl ether | 2 |
| 4-tert-butyl-4' - -methoxydibenzoylmethane | 1.2 |
| Octyl methoxycinnamate | 2.4 |
| Acrylic ester/steareth-20 methacrylate copolymers | 1 |
| Saccharide isomerate | 1 |
| Water (W) | To 100 |
In summary, it is apparent from the above examples and description that topical compositions comprising saccharide isomerate provide microbiome balance when applied to human surfaces. It was found that the thus obtained balance of the microbiome is achieved by the carbohydrate isomers acting as prebiotics. The saccharide isomers preferentially promote the growth of commensal bacteria such as staphylococcus epidermidis, as compared to harmful/potentially harmful bacteria such as staphylococcus aureus. It was found that the main metabolite in the fermentation of saccharide isomerate is lactic acid, which contributes to the natural defense system of human body surfaces (e.g. skin, scalp including hair, armpits and oral cavity).
Claims (6)
1. Use of a topical composition comprising saccharide isomers as prebiotics when applied on a human surface.
2. Use according to claim 1, wherein the composition comprises 0.001-10 wt% saccharide isomers.
3. Use according to claim 1 or 2, wherein the composition further comprises 0.001-10 wt% of other prebiotics.
4. Use according to claim 3, wherein the other prebiotics are selected from polyols, monosaccharides, disaccharides, oligosaccharides, polysaccharides and mixtures thereof.
5. Use according to any one of the preceding claims, wherein the human body surface is at least one of skin, scalp including hair, axilla and oral cavity.
6. The use according to any one of the preceding claims, wherein the use is non-therapeutic.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18193684 | 2018-09-11 | ||
| EP18193684.0 | 2018-09-11 | ||
| PCT/EP2019/072119 WO2020052916A1 (en) | 2018-09-11 | 2019-08-19 | A topical composition comprising saccharide isomerate for microbiome balancing |
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| CN112672728A true CN112672728A (en) | 2021-04-16 |
| CN112672728B CN112672728B (en) | 2023-10-27 |
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| CN201980059378.XA Active CN112672728B (en) | 2018-09-11 | 2019-08-19 | Topical compositions comprising saccharide isomerate for microbiome balance |
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|---|---|
| EP (1) | EP3849509A1 (en) |
| CN (1) | CN112672728B (en) |
| WO (1) | WO2020052916A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020216757A1 (en) | 2019-04-25 | 2020-10-29 | Universiteit Gent | Prebiotic skin care compositions containing carboxylic acids |
| EP4210836A1 (en) * | 2020-09-10 | 2023-07-19 | DSM IP Assets B.V. | Novel use of saccharide isomerate |
| JP2023551889A (en) * | 2020-12-02 | 2023-12-13 | ユニリーバー・アイピー・ホールディングス・ベスローテン・ヴェンノーツハップ | topical disinfectant composition |
| WO2022136864A1 (en) | 2020-12-22 | 2022-06-30 | Reckitt Benckiser Health Limited | Topical wash composition |
| KR102548896B1 (en) * | 2021-03-03 | 2023-06-27 | 주식회사 엘지생활건강 | Cosmetic composition for skin improvement through control of porphyrin production and hyaluronic acid degradation enzyme |
| GB202104969D0 (en) | 2021-04-08 | 2021-05-26 | Givaudan Sa | Fragrance composition |
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| CN104105470A (en) * | 2012-02-14 | 2014-10-15 | 宝洁公司 | Topical use of a skin-commensal prebiotic agent and compositions containing the same |
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| CN107949368A (en) * | 2015-07-28 | 2018-04-20 | 玫琳凯有限公司 | Topical skin preparations |
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| WO1997030690A1 (en) | 1996-02-23 | 1997-08-28 | Unilever Plc | Skin treatment with salicylic acid esters |
| US5766575A (en) | 1996-06-14 | 1998-06-16 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Method and composition for skin lightening |
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- 2019-08-19 WO PCT/EP2019/072119 patent/WO2020052916A1/en active Search and Examination
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|---|---|
| WO2020052916A1 (en) | 2020-03-19 |
| EP3849509A1 (en) | 2021-07-21 |
| CN112672728B (en) | 2023-10-27 |
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