WO2021104643A1 - Composition d'agent conservateur - Google Patents

Composition d'agent conservateur Download PDF

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Publication number
WO2021104643A1
WO2021104643A1 PCT/EP2019/083090 EP2019083090W WO2021104643A1 WO 2021104643 A1 WO2021104643 A1 WO 2021104643A1 EP 2019083090 W EP2019083090 W EP 2019083090W WO 2021104643 A1 WO2021104643 A1 WO 2021104643A1
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Prior art keywords
hydroxy
hydroxymethyl
preservative composition
hydroxyethyl
piperazine
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PCT/EP2019/083090
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English (en)
Inventor
Irena JEVTOV
Original Assignee
Curious D.O.O.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Curious D.O.O. filed Critical Curious D.O.O.
Priority to PCT/EP2019/083090 priority Critical patent/WO2021104643A1/fr
Publication of WO2021104643A1 publication Critical patent/WO2021104643A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/16—Heavy metals; Compounds thereof

Definitions

  • the present invention relates to a preservative composition used as an industrial product for antimicrobial preservation of various water-based cosmetic, pharmaceutical, and chemical formulations.
  • the present invention solves the technical problem of antimicrobial preservation of various water-based cosmetic, pharmaceutical, and chemical products, and is of:
  • composition in the present invention provides no known toxicity to humans, while maintaining high efficacy against microbial growth in water-based product formulations.
  • Cosmetic and pharmaceutical products containing water require preservation against microbial contamination.
  • the preservation ensures the safety of consumers or patients from potentially pathogenic microorganisms and increases the product's shelf-life by preventing biological and physicochemical deterioration.
  • the preservation is achieved by multiple strategies, including the use of antimicrobial agents acting as preservatives against microbial spoilage.
  • Preservatives commonly used are various synthetic or natural compounds or multifunctional ingredients.
  • antimicrobial preservatives are methyl 4-hydroxybenzoate, ethyl 4-hydroxybenzoate, n-propyl 4-hydroxybenzoate collectively known as parabens, methylisothiazolinone, organic acids such as benzoic or sorbic acid, formaldehyde releasers like imidazolidinyl urea, phenols such as triclosan, quaternary ammonium surfactants like benzalkonium chloride, bisbiguanides such as chlorhexidine digluconate and others; see literature references 1 and 2:
  • Zinc bis-glycinate (1) or its monohydrate form is a known salt and complex of zinc (Zn 2+ ) and amino acid glycine:
  • Compound 1 is commonly used as a nutritional source of the essential micro mineral zinc. Among its other known roles, it was described as an antimicrobial agent. Thompson disclosed the method for inhibiting microbial growth by the use of zinc chelate consisting of zinc lipoate and zinc bis-glycinate (1). This agent is claimed to be effective against various Gram-negative and Gram-positive bacteria and fungi, more specifically, against Staphylococcus aureus, Streptococcus pyogenes, Salmonella typhimurium, Escherichia coli, and Candida albicans; see literature reference 4:
  • Arndt described the use of various other zinc salts, including compound 1, as one of the components in a two-component concept of the antibacterial and antifungal composition.
  • One component is a zinc salt, while another one is a ligand which forms a complex with the zinc salt.
  • Such combination provides enhanced antibacterial and antifungal effect; see literature reference 5: 5) US 2014/0179645 A1; Antimicrobial compositions; inventor: D. C. Arndt; applicant: The Pisces Group LLC (US); priority date: 21. 12. 2012.
  • X X'
  • DKP diketopiperazine
  • DKP derivative 3,6-di(2- hydroxyethyl) piperazine-2,5-dione (3a) can be formed from two moles of 2-hydroxy ethyl-glycine (homoserine) or aspartic acid derivative whose terminal carboxyl group (COOH) is previously reduced to alcohol group (CH 2 0H).
  • DKP derivatives are found within various probiotic metabolic products that exhibit antimicrobial effects against some pathogenic microorganisms.
  • Dal Bello and co-workers disclosed the chemical composition of secondary metabolites from probiotic bacteria Lactobacillus plantarum FST 1.7. They found that, among other metabolites, the bacteria produce and release DKP derivatives dysfunctioncyclic dipeptides ("ofu) (DKP L- Pro-L-Leu) or L-phenylalanine (Phe) (DKP L-Pro-L-Phe) .
  • These metabolites exhibit some antifungal effects that can be used for the preservation of food, including bread; see literature reference 8.
  • polyols of general formula II with linear- or branched-chain aliphatic hydrocarbon skeleton R with 5-18 carbon atoms and 4-8 hydroxyl (OH) groups in the molecule e.g., 5-hydroxy methyl-1,5,6,7,11-undecane-pentol (2); and,
  • the invention describes the antimicrobial preservative composition for use in cosmetic, pharmaceutical, and chemical products.
  • the preservative composition according to the present invention, consists of:
  • polyols of general formula II with linear- or branched- chain aliphatic hydrocarbon skeleton R with 5-18 carbon atoms and 4-8 hydroxyl (OH) groups in the molecule e.g., 5-hydroxymethyl-l,5,6,7,11-undecane-pentol (2 ) ; from 0.5-90% w/w;
  • substitution groups X, X' are the same or different, and selected from the group consisting of: hydrogen (H-), methyl (CH 3 -), hydroxymethyl (HOCH 2 -), ethyl (C 2 H 5 -), 1-hydroxyethyl [CH 3 CH(OH)-], 2-hydroxy ethyl (HOCH 2 CH 2 -), 1,2-dihydroxyethyl [HOCH 2 CH(OH)-], n- propyl (CH 3 CH 2 CH 2 -), 3-hydroxypropyl (HOCH 2 CH 2 CH 2 -), isopropyl [(CH 3 ) 2 CH—], 2-hydroxyisopropyl [HOCH(CH 3 )CH 2 -], 1,3-dihydroxypropan-2-yl [(HOCH 2 ) 2 CH-], 2-methylpropyl [CH 3 CH(OKs)CH 2 -], l-hydroxy-2-methylpropyl
  • composition is used in concentrations from 0.1-20% w/w in water- based cosmetic, pharmaceutical, and chemical products to prevent their microbial spoilage.
  • the present invention relates to an improved industrial product in the field of antimicrobial preservatives for water-based cosmetic, pharmaceutical, and chemicals products.
  • the preservative composition according to the present invention consists of:
  • substitution groups X, X' are the same or different, and selected from the group consisting of: hydrogen (H-), methyl (CH 3 -), hydroxymethyl (HOCH 2 -), ethyl (C 2 H 5 -), 1-hydroxyethyl [CH 3 CH(OH)-], 2-hydroxy ethyl (HOCH 2 CH 2 -), 1,2-dihydroxyethyl [HOCH 2 CH(OH)-], n- propyl (CH 3 CH 2 CH 2 -), 3-hydroxypropyl (HOCH 2 CH 2 CH 2 -), isopropyl [(CH 3 ) 2 CH—], 2-hydroxyisopropyl [HOCH(CH 3 )CH 2 -], 1,3-dihydroxypropan-2-yl [(HOCH 2 ) 2 CH-], 2-methylpropyl [CH 3 CH(OKs)CH 2 -], l-hydroxy-2-methylpropyl
  • the excipients B. are selected from the following groups:
  • liquid diluents water, glycerol, mixtures of water and glycerol;
  • wetting agents polysorbates, poloxamers, lecithins, sorbitan esters;
  • pH adjusting agents citric acid, malic acid, sodium hydroxide, trisodium citrate or its dihydrate;
  • anti-caking agents colloidal silicon dioxide, sodium aluminium silicate.
  • the principal and the secondary active ingredients in the preservative composition are selected to be:
  • polyol 5-hydroxymethyl-l,5,6,7,11-undecane-pentol ( 2 ) ; from 20-50% w/w; and,
  • the secondary active ingredient is selected to be 5-hydroxymethyl-l,5,6,7,11-undecane- pentol (2 ) , from 0.5-90% w/w.
  • the secondary active ingredient is selected to be 3,6-di(2-hydroxyethyl) piperazine-2,5-dione (3a) , from 0.5-90% w/w.
  • the secondary active ingredients are selected to be 5-hydroxymethyl- 1,5,6,7,11-undecane-pentol (2 ) , from 0.5-90% w/w; and 3,6-di(2- hydroxyethyl) piperazine-2,5-dione (3a) , from 0.5-90% w/w.
  • the preservative composition consists of the principal and the secondary active ingredients only; up to 100% w/w, without excipients.
  • Said composition is selected to be:
  • Polyols of general formula II with linear- or branched-chain aliphatic hydrocarbon skeleton R with 5-18 carbon atoms and 4-8 hydroxyl (OH) groups in the molecule can be used in all commercially available forms. Some of them are liquids, and others are solids. In the final form of the preservative composition, they are mixed with other active ingredients (i) and possibly (iii) and optionally with some of the auxiliary ingredients (excipients) (iv)- (ix) to form either a solid or a liquid.
  • the said 5-hydroxymethyl-l,5,6,7,11-undecane-pentol (2 ) can be used.
  • 3,6-Di(substituted)piperazine-2,5-diones III or diketopiperazines are basically cyclic dipeptides, the derivatives of two molecules of the same (symmetrical DKP) or different (unsymmetrical DKP) a-amino acids IV, where X, X' is the residual moiety X (X') of the parent a-amino acid(s).
  • the preservative composition from the present invention can be formulated either as a homogeneous mixture of the principal active ingredient, compound 1, with one or more secondary active ingredients from the group (ii) and/or (iii), or, as a complex formulation with one or more above-defined auxiliary ingredients (excipients).
  • Wetting agents are selected from the groups consisting of polysorbates such as polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate 80; poloxamers, such as various symmetrical triblock copolymers of polyethylene oxide (PEO) and polypropylene oxide (PPO) of general formula (PEO) a ( PPO) b ( PEO) a , wherein the value for a and b can be different; e.g.
  • lecithins such as soybean [Glycine max (L.) Merr.] lecithin, sunflower (Helianthus annuus L.) lecithin, hydrolyzed soybean lecithin, hydrolized sunflower lecithin; sorbitan esters such as sorbitan laurate, sorbitan palmitate, sorbitan stearate, and sorbitan oleate.
  • the preservative composition from the present invention can be a flowable powder or a liquid (either as a solution or suspension).
  • results of preservative efficacy of the composition from the present invention The preservative efficacy of the composition from the present invention was analyzed using the standard method in cosmetics microbial challenge test - against the following strains:
  • Candida albicans (C. albicans) ATCC 10231; and,
  • the cosmetic base for the microbial challenge tests was an oil-in water (O/W) emulsion (like a body cream).
  • O/W oil-in water
  • Table 1 The formulation of the base O/W emulsion is shown in Table 1, and the preparation is described in Example 1 in the experimental section.
  • the unpreserved sample of the O/W emulsion was used as a control. Additional controls were the active substances, compounds 1, 2, and 3a, individually added to the base O/W emulsion and analyzed; see Table 2.
  • the composition of the control and testing samples are shown in Table 2.
  • Example 6 Experimental procedure for the microbial challenge test of the control and the preserved emulsion from the present invention (Examples 2-4) is described in Example 6. The average results are shown in Tables 3-6.
  • zinc bis-glycinate (1) acts as an effective antimicrobial agent at the concentration of 0.25% w/w in the formulation of the base O/W emulsion against all tested microorganisms except P. aeruginosa where it showed no effect and S. aureus where its effect weakens throughout the duration of the test; see Table 3.
  • the selected polyol, 5-hydroxymethyl-l,5,6,7,11-undecane-pentol (2 ) , in the concentration 0.35% w/w, in the base O/W emulsion shows weak antimicrobial effect against three microorganisms, but does not affect P. aeruginosa and A. brasiliensis; see Table 3.
  • Table 3 Results of microbial challenge testing for individual active substances from the preservative composition of the present invention. The antimicrobial effects are shown for zinc bis-glycinate (1), 5-hydroxymethyl-l,5,6,7,11- undecane-pentol (2 ) and 3,6-di(2-hydroxyethyl)piperazine- 2,5-dione ( 3a) and compared to unpreserved base emulsion.
  • CFU colony forming units
  • TO the initial inoculum number
  • 7d MB count of CFU/g after 7 days
  • 14d MB count of CFU/g after 14 days
  • 28d MB count of CFU/g after 28 days
  • log c log change relative to the initial inoculum number value
  • Control-1 unpreserved base O/W emulsion,
  • 1 base O/W emulsion with 0.25% w/w zinc bis-glycinate (1)
  • 2 base O/W emulsion with 0.35% w/w 5- hydroxymethyl-1,5,6,7,11-undecane-pentol (2)
  • the antimicrobial effects of the preservative composition from the present invention were tested.
  • the mixture of zinc bis- glycinate (1; 0.25% w/w) and 5-hydroxymethyl-l,5,6,7,11-undecane- pentol (2; 0.5% w/w) as the selected polyol II (product described in Example 2) showed significant synergic antimicrobial effects, evident as an effect on P. aeruginosa and full suppression of S. aureus, wherein individual compound 1 was not active.
  • aeruginosa in the preservative composition from the present invention was in the range of 10 2 lower (see Table 4) compared to either individual compound 1 or unpreserved base O/W emulsion (see Table 3).
  • the result suggests a synergic effect of polyol 2 on antimicrobial activity of compound 1 against tested microorganisms.
  • the preservative composition from the present invention, the product described in Example 2 eliminated all other tested microorganisms, and no viable CFU could be isolated.
  • the mixture of zinc bis-glycinate (1; 0.25% w/w) and 3,6- di(2-hydroxyethyl)piperazine-2,5-dione (3a; 0.50% w/w) as the selected DKP derivative also exhibited significant synergic antimicrobial effects against P. aeruginosa and S. aureus.
  • the product of Example 3 also showed about 10 2 reduction of CFU value for P. aeruginosa and complete supression of S. aureus compared to either compound 1 (see Table 3) or the unpreserved O/W emulsion; see Table 4.
  • the efficacy of the preservative composition from the present invention, the product described in Example 3 was also effective against all other tested microorganisms, wherein no viable CFU could be isolated.
  • CFU colony forming units
  • TO initial inoculum number
  • 7d MB count of CFU/g after 7 days
  • 14d MB count of CFU/g after 14 days
  • 28d MB count of CFU/g after 28 days
  • log c log change relative to initial inoculum number value
  • Control-1 unpreserved base O/W emulsion, without any active substance
  • CFU colony forming units
  • TO initial inoculum number
  • 7d MB count of CFU/g after 7 days
  • 14d MB count of CFU/g after 14 days
  • 28d MB count of CFU/g after 28 days
  • log c log change relative to initial inoculum number value
  • Control-1 unpreserved base O/W emulsion
  • the ternary composition of zinc bis-glycinate (1; 0.25% w/w), 5-hydroxymethyl-l,5,6,7,11-undecane-pentol (2; 0.50% w/w) as selected model polyol, and 3,6-di(2-hydroxyethyl)piperazine-2,5- dione (3a; 0.5% w/w) as selected model DKP derivative exhibited significant synergic antimicrobial effects against all tested microorganisms, especially against P. aeruginosa.
  • the similar decrease of CFU value at the range of 10 2 was observed after 28 days of the challenge test, compared to the CFU value determined for either compound 1 or the unpreserved O/W emulsion; see Table 3 and Table 5.
  • the preservative composition from the present invention, product of Example 4 was also effective against all other tested microorganisms, wherein no viable CFU could be isolated, except for A. brasiliensis that showed some viability at day 28.
  • CFU colony forming units
  • TO initial inoculum number
  • 7d MB count of CFU/g after 7 days
  • 14d MB count of CFU/g after 14 days
  • 28d MB count of CFU/g after 28 days
  • log c log change relative to initial inoculum number value
  • Control-1 unpreserved base O/W emulsion
  • the process of preparation of the preservative composition according to the present invention includes the homogenization of:
  • auxiliary ingredients for the preparation of the preservative composition from the present invention in the liquid form, such as solution or suspension, the following auxiliary ingredients (excipients) can be used: (iv) liquid diluents: water, glycerol, mixtures of water and glycerol;
  • suspending agents methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methycellulose, xanthan gum;
  • wetting agents polysorbates, poloxamers, lecithins, sorbitan esters; and if needed,
  • pH adjusting agents citric acid, malic acid, sodium hydroxide, trisodium citrate, or its dihydrate.
  • the following excipients can be used:
  • anti-caking agents colloidal silicon dioxide, sodium aluminium silicate.
  • the preservative composition from the present invention is used in the production of water-based cosmetic, pharmaceutical, household, or chemical formulations to protect against their microbial spoilage.
  • the preservative composition from the present invention acts as an antimicrobial agent. It shows a biocidal effect at the upper end of the proposed concentrations and biostatic at the lower end of the recommended levels. It is active against bacteria, yeasts, and molds in various water-based products that are due to high water content, prone to microbial spoilage.
  • the preservative composition from the present invention is typically used in concentrations from 0.1-20% w/w within the formulation of the final product.
  • the term fluffyroom temperature relates to a temperature range of 20-25 °C.
  • the mixing speed is expressed as the number of revolutions of the bin per minute (rpm).
  • CFU means colony-forming units, which is the number of viable cells in a given sample.
  • the starting raw materials were purchased from the following suppliers: zinc bis-glycinate (1) from Ambinter (FR); 5- (hydroxymethyl ) -1,5,6, 7,11-undecanepentol (2 ) and 3,6-di(2- hydroxyethyl ) piperazine-2,5-dione (3a) from Merck AG (DE) ; purified water from Adrialab Ltd (HR); carbomer and colloidal silicon dioxide from Evonik Industries AG (DE); xanthan gum from Fagron (HR); glycerol from Emery Oleochemicals GmbH (DE); cetostearyl alcohol from BTC Europe GmbH; Myritol caprylic/capric triglyceride from BASF AG (DE); sunflower seed oil from Henry Lamotte Oils GmbH (DE); dimethicone from Dow Corning GmbH (DE); hydrogenated polyisobutene (and) sucrose polystearate from BASF AG (DE); glyceryl stearate from BTC Europe GmbH; sodium hydroxide solution (20%
  • carbomer and xanthan gum are dispersed in water and heated to 70-75 °C, when glycerine is added (this is Phase-1).
  • Cetearyl alcohol, caprylic/capric triglyceride, Helianthus annuus (sunflower) seed oil, dimethicone, sucrose polystearate (and) hydrogenated polyisobutene and glyceryl stearate are mixed separately and also heated to 70-75 °C until everything is melted and mixed (Phase-2).
  • Phase-2 is slowly added to Phase-1 at 70-75 °C temperature, and all is mixed until uniform.
  • the mixture is cooled down to 60 °C, and the pH is adjusted with an aqueous solution (20% w/w) of sodium hydroxide (NaOH) to pH 6.0-6.5.
  • the mixture is further cooled down with mixing to room temperature, and the pH is again adjusted to pH 6.0-6.5, if necessary.
  • the product is white, almost odorless O/W emulsion.
  • the formulation of the base O/W emulsion is given in Table 1.
  • Example 2 Preparation of the preservative composition from the present invention based on 10% w/w zinc bis-glycinate (1) and 20% w/w 5-hydroxymethyl-l,5,6,7,11-undecane-pentol (2)
  • composition for 100 g solution:
  • Example 3 Preparation of the preservative composition from the present invention based on 10% w/w zinc bis-glycinate (1) and 20% w/w 3,6-di(2-hydroxyethyl)piperazine-2,5-dione (3a)
  • composition for 100 g solution:
  • Example 4 Preparation of the composition from the present invention based on 10% w/w zinc bis-glycinate (1), 20% w/w 5-hydroxymethyl-
  • composition for 100 g solution:
  • Preparation Purified water is added to compounds 1, 2, and 3a and dissolved by rocking at room temperature for half to one hour.
  • the product is in the form of an opaque white-to-yellow solution with a faint oily odor.
  • Example 5 Preparation of the composition from the present invention based on 10% w/w zinc bis-glycinate (1), 20% w/w 5-hydroxymethyl- 1,5,6,7,11-undecane-pentol (2), and 50% w/w 3,6-di(2-hydroxyethyl) piperazine-2,5-dione (3a)
  • composition for 100 g free-flowing powder:
  • Preparation Previously weighted components (1-4) are combined in the overhead stirrer and homogenized by mixing for 15 minutes at 200 rpm. Powder product obtained in this way is further de-agglomerated by passing through a conical mill equipped with 1 mm sieve. The product is in the form of white-to-yellow free-flowing powder with a faint oily odor.
  • Example 6 Microbial challenge test of the preservative composition from the present invention
  • Candida albicans (C. albicans) ATCC 10231; and,
  • the testing was performed using the base oil-in-water (O/W) cosmetic cream-like emulsion that is a suitable medium for microbial growth.
  • the formulation of the base O/W emulsion is shown in Table 1, and its preparation is described in experimental Example 1.
  • the unpreserved base O/W emulsion as well as the formulations obtained by mixing in of individual active substances, compounds 1, 2, and 3a, in the base O/W emulsion were used; see
  • Bacteria P. aeruginosa, S. aureus, E. coli
  • TSA tryptic soy agar
  • yeast C. albicans on Sabouraud dextrose agar
  • PDA Sabouraud dextrose agar
  • mold A. brasiliensis at Potato dextrose agar (PDA) at 22.512.5 °C.
  • the microorganisms are harvested and washed with sterile saline solution. The number of microorganisms for inoculation was adjusted to Ixl0 5 -lxl0 6 CFU/ml for bacteria and Ixl0 4 -lxl0 5 CFU/ml for fungi.
  • each active substance was first dissolved in purified water. Specifically, 5-(hydroxymethyl)-1,5,6,7,11- undecanepentol (2) was dissolved in purified water as the 50% solution, whilst 3,6-di(2-hydroxyethyl) piperazine-2,5-dione (3a) , and zinc bis-glycinate (1) each as 10-20% w/w solutions, all at room temperature. The pH value of each solution was tested and adjusted with citric acid to pH 6-6.5 if needed. The dissolved active components are added at the end of formulation preparation, at a temperature of 40 °C and thoroughly mixed into the formulation while cooling.
  • Zinc bis-glycinate (1 ) was added to the final formulation at 0.25% w/w, while 5- (hydroxymethyl)-1,5,6,7,11-undecanepentol (2) and 3,6-di(2- hydroxyethyl) piperazine-2,5-dione (3a) were added at at 0.35% w/w and 0.8% w/w, respectively.
  • Preservative compositions from the present invention in the final forms described in Examples 2-4 were added in the same manner into the base O/W emulsion, at the concentrations corresponding to:
  • Example 2 (ii) 0.25% w/w of the compound 1 and 0.5% of the compound 3a; Example 3; and,
  • each test sample (except for A. brasiliensis that is omitted at 7d) is plated by spreading of a determined amount on agar plates in duplicates. The plates are incubated at 32.512.5 °C for 48-72 hours for bacteria and at 22.512.5 °C for fungi. The growth of yeast C. albicans is counted after 48-72 hours, and the mold A. brasiliensis after 3-5 days.
  • the preservative composition from the present invention based on the mixture of:
  • polyols of general formula II with linear- or branched-chain aliphatic hydrocarbon skeleton R with 5-18 carbon atoms and 4-8 hydroxyl (OH) groups in the molecule e.g., 5-hydroxy methyl-1,5,6,7,11-undecane-pentol (2); from 0.5-90% w/w;
  • the preservative composition from the present invention represents an effective and safe alternative to existing conventional preservatives that are of medium-to-high toxicological concern.
  • the present invention also clearly surpasses the efficacy of zinc bis-glycinate (1), as the only antimicrobial agent (see literature references 4-6).
  • the preservative composition from the present invention is used in the manufacturing of various water-based cosmetic, pharmaceutical, or chemical products as a preservative against their microbiological spoilage. In this manner, the industrial applicability of the present invention is obvious.

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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
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Abstract

La présente invention concerne une composition d'agent conservateur pour la conservation antimicrobienne de divers produits cosmétiques, pharmaceutiques et chimiques à base d'eau. La composition est constituée de principes actifs choisis pour être le bis-glycinate de zinc ou son monohydrate et un ou plusieurs autres principes actifs choisis dans le groupe constitué par les polyols ayant un squelette hydrocarboné aliphatique à chaîne linéaire ou ramifiée contenant de 5 à 18 atomes de carbone et de 4 à 8 groupes hydroxyle (OH) dans la molécule, par exemple, le 5-hydroxyméthyl -1,5,6,7,11-undécane-pentol, ainsi que le 3,6-di(substitué)pipérazine-2,5-diones, par exemple, 3,6-di(2-hydroxy éthyl)pipérazine -2,5-dione, et éventuellement un ou plusieurs excipients. Les excipients sont choisis dans le groupe suivant : des diluants liquides, des agents de suspension, des agents mouillants, des tampons, des diluants solides et des antiagglomérants.
PCT/EP2019/083090 2019-11-29 2019-11-29 Composition d'agent conservateur WO2021104643A1 (fr)

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Citations (6)

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