DE202013104382U1 - Liquid concentrate for the antimicrobial treatment of topically applied products - Google Patents

Abstract

Liquid concentrate containing a) 20-70% by weight of 3-phenylpropan-1-ol, b) 10-50% by weight of octanediol-1,2, c) 15-60% by weight of 1,3-propanediol and d) optionally up to 2000 ppm of one or more antioxidants.

Description

The present invention relates to a liquid concentrate for the protection of products for topical application from microbial attack. Furthermore, the invention relates to corresponding antimicrobial products.

Preservatives for topically applied products such as cosmetics are known but often have disadvantages. Some of the active substances contained, for example formaldehyde releasers, parabens or isothiazolinones, are being discussed critically. Their use in topically applicable products is correspondingly undesirable. Organic acids can only be used effectively in low pH products, so their uses are limited. In some cases, these agents are also allergens, such. As benzyl alcohol with a poor storage stability as a raw material and in the concentrate, which also lead as a concentrate (and sometimes in so-equipped products) to a distinct odor.

Further, the antimicrobial effects of aromatic alcohols (such as phenoxyethanol or benzyl alcohol and combinations with phenethyl alcohol and combinations with phenylpropanol) and polyhydric alcohols are known. The EP 0 524 548 A1 discloses, for example, combinations of antimicrobial aromatic alcohols with antimicrobially active 1,2- or 1,3-diols.

In addition, topically applied products can be antimicrobially equipped (preserved) with octanediol-1,2 (caprylyl glycol). Octanediol-1,2 is an active ingredient which is frequently used in cosmetic preservation, since it offers particular effectiveness against mold. However, since the melting point of the diol is about 37 ° C, the raw material is solid at room temperature, which complicates its incorporation and dosage in products. Desired are liquid concentrates with a high content of octanediol-1,2, which can exhibit a certain low temperature stability.

The WO 2008/061187 A1 discloses preservative compositions containing propanediol-1,3, optionally mixed with glycols. The examples also describe mixtures of 1,3-propanediol with octanediol-1,2 and phenoxyethanol. However, there is concern about the use of phenoxyethanol because this aromatic alcohol is said to be absorbed through the skin. Phenoxyethanol is therefore undesirable in cosmetics especially for children and infants.

Further, the product Fenicap ^® (Sinerga, Milano, Italy) is known, which comprises 3-phenylpropan-1-ol (hydrocinnamic alcohol), and octanediol-1,2. This concentrate (from 35 to 45% octanediol-1,2 and 65 to 55 wt .-% 3-phenylpropan-1-ol) contains an advantageously high amount of octanediol-1,2, but is inadequate in terms of its low temperature stability. This means that octanediol-1,2 can crystallize out on storage. The concentrate must therefore be heated after transport at low temperatures, if necessary, so that it can then be metered into a cosmetic.

In addition, the product known Dermosoft ^® OMP (Dr. Straetmans GmbH, Hamburg, Federal Republic of Germany) which, octanediol-1,2, and 3-phenylpropane-1-ol comprises 2-methyl propane-1,3. Because of the small content of octanediol-1,2 (15%) and 3-phenylpropan-1-ol (3%), the recommended amount is 2 to 4 wt .-%, while in cosmetics, a use concentration of antimicrobial agent of 1 ± 0 , 5 wt .-% is common. Moreover the recommended use concentration of up to 4 brings in the equipped with Dermosoft ^® OMP product an undesirably high amount of solvent 2-methyl propane diol-1,3 wt .-%.

Further, the product Sensiva SC 10 ^® is known to the Schulke & Mayr GmbH (Norderstedt, Federal Republic of Germany), 70 wt% octanediol-1,2, and 30 .-% of 1- (2-ethylhexyl) comprises glycerin. The concentrate thus contains a desired high level of octanediol-1,2, and further comprises the skin care and deodorant 1- (2-ethylhexyl) glycerol. However, there is a need for concentrates for the antimicrobial finishing of cosmetics that do not necessarily contain 1- (2-ethylhexyl) glycerol ethers. In addition, the critical crystallization temperature of this liquid concentrate is about 15 ° C, which means that it often has to be heated by the customer after transport to 25-30 ° C in order to incorporate it into a cosmetic product can.

Accordingly, it was an object of the present invention to provide a concentrate with a high content of octanediol-1,2. The concentrate should not tend to solidify even after prolonged storage below 0 ° C (as below -5 ° C). It should act in the typical use concentration of 1.0 ± 0.5% in cosmetics antimicrobial, and it should be the cosmetic against attack by mold, yeasts and protect bacteria. Furthermore, the concentrate should contain no unwanted in cosmetics other ingredients in high amounts. For example, the concentrate should not necessarily contain phenoxyethanol. In addition, the concentrate should not necessarily contain glycerol ethers, such as 1- (2-ethylhexyl) glycerol ether.

• a) 20 bis 70 Gew.-% 3-Phenylpropan-1-ol,
• b) 10 bis 50 Gew.-% Octandiol-1,2,
• c) 15 bis 60 Gew.-% Propandiol-1,3 und
• d) gegebenenfalls bis 2000 ppm von einem oder mehreren Antioxidantien umfasst.

It has now surprisingly been found that this object is achieved by a liquid concentrate, the

• a) from 20 to 70% by weight of 3-phenylpropan-1-ol,
• b) from 10 to 50% by weight of octanediol-1,2,
• c) 15 to 60 wt .-% of 1,3-propanediol and
• d) optionally up to 2000 ppm of one or more antioxidants.

The liquid concentrate according to the invention achieves the abovementioned object and is distinguished, in particular, by the fact that it does not undergo any (complete) crystallization over an extended period of time during storage at low temperature, such as 0 ° C. or even -5 ° C. of the contained octanediol-1,2. In addition, the concentrate containing the components a) to c) contains predominantly natural or nature-identical substances and, if desired, for. B. be protected with vitamin E as an antioxidant against formation of undesirable degradation products. Thus, by concentrates according to the invention in the antimicrobial finishing of products for topical application (such as medical creams and cosmetics) no unwanted components are introduced.

In a preferred embodiment, the concentrate consists of components a) to c) and optionally d), d. H. In this preferred embodiment, in addition to constituents a) to c) and optionally d), no further constituents are present in the concentrate according to the invention.

In a further preferred embodiment, the concentrate a) according to the invention comprises 30 to 60% by weight of 3-phenylpropan-1-ol, preferably 40 to 50% by weight, such as 45% by weight.

It is further preferred that the concentrate b) comprises from 15 to 40% by weight of octanediol-1,2, preferably from 20 to 30% by weight, such as about 25% by weight.

In addition, it is preferred that the concentrate c) according to the invention comprises from 20 to 45% by weight of 1,3-propanediol, preferably from 25 to 35% by weight, such as about 30% by weight.

Optionally, liquid concentrates according to the invention optionally contain d) up to 2000 ppm of one or more antioxidants. It is preferred that the antioxidant is selected from phenolic compounds such as 3-tert-butyl-4-hydroxyanisole, 2,6-di-tert-butyl-p-cresol, dodecyl gallate, pyrogallate, tocopherol (eg vitamin E) and its derivatives (eg, vitamin E acetate), as well as mixtures of these antioxidants, preferably vitamin E and its derivatives, particularly preferably vitamin E.

It is further preferred that the amount of component d), d. H. the total amount of the one or more antioxidants is from 20 to 400 ppm, preferably from 50 to 300 ppm, especially from 80 to 200 ppm, such as about 100 ppm, by weight of the concentrate.

It is preferred that the liquid concentrate according to the invention comprises no glycerol ether, in particular non-1- (2-ethylhexyl) glycerol ether. It is further preferred that the concentrate according to the invention does not comprise phenoxyethanol.

• a) 40–50 Gew.-% (wie etwa 45 Gew.-%) 3-Phenylpropan-1-ol,
• b) 20 bis 30 Gew.-% (wie etwa 25 Gew.-%) Octandiol-1,2,
• c) 25 bis 35 Gew.-% (wie etwa 30 Gew.-%) Propandiol-1,3 und
• d) gegebenenfalls 50 bis 300 ppm (insbesondere 80 bis 200 ppm, wie etwa 100 ppm) von einem oder mehreren Antioxidantien.

In a first particularly preferred embodiment, the concentrate comprises

• a) 40-50% by weight (such as 45% by weight) of 3-phenylpropan-1-ol,
• b) 20 to 30% by weight (such as 25% by weight) of octanediol-1,2,
• c) 25 to 35 wt .-% (such as about 30 wt .-%) of 1,3-propanediol and
• d) optionally 50 to 300 ppm (especially 80 to 200 ppm, such as 100 ppm) of one or more antioxidants.

• a) 40–50 Gew.-% (wie etwa 45 Gew.-%) 3-Phenylpropan-1-ol,
• b) 20 bis 30 Gew.-% (wie etwa 25 Gew.-%) Octandiol-1,2,
• c) 25 bis 35 Gew.-% (wie etwa 30 Gew.-%) Propandiol-1,3 und
• d) gegebenenfalls 50 bis 300 ppm (insbesondere 80 bis 200 ppm, wie etwa 100 ppm) von einem oder mehreren Antioxidantien.

In a second particularly preferred embodiment, the concentrate consists of

• a) 40-50% by weight (such as 45% by weight) of 3-phenylpropan-1-ol,
• b) 20 to 30% by weight (such as 25% by weight) of octanediol-1,2,
• c) 25 to 35 wt .-% (such as about 30 wt .-%) of 1,3-propanediol and
• d) optionally 50 to 300 ppm (especially 80 to 200 ppm, such as 100 ppm) of one or more antioxidants.

With concentrates according to the invention, leave-on and rinse-off formulations can be preserved for medical purposes or for cosmetics (ie equipped with antimicrobials). Phenoxyethanol-containing preservatives can be replaced. Because the compulsory ingredients in the concentrate according to the invention show further advantageous properties in topical application, ie are multifunctional, it is also possible to claim products that are antimicrobially finished according to the invention as preservative-free products.

The invention further relates to an antimicrobially finished product for topical application, which comprises 0.2 to 3.0 wt .-% of the concentrate, preferably 0.3 to 2.0 wt .-%, in particular 0.5 to 1.5 wt .-%. Preferably, the product is a cream.

• – Gute Kältestabilität bei hoher Wirkstoffkonzentration
• – Flüssige Variante von 1,2-Octandiol
• – Sehr gute Wirksamkeit bei niedriger Einsatzkonzentration
• – verbesserte Wirksamkeit im Vergleich mit den Einzelkomponenten
• – verbesserter Geruch gegenüber einer gleich großen Konzentration an 3-Phenylpropan-1-ol
• – verbesserte Hautverträglichkeit gegenüber der für gleich gute Wirksamkeit nötigen 1,2-Octandiol-Konzentration
• – verbesserte Lagerstabilität durch Zusatz von Antioxidantien möglich, dadurch Vermeidung eventueller unerwünschter Abbauprodukte auch in topisch anzuwendenden Produkten
• – hoher Anteil an natürlichen (1,3-Propandiol) oder naturidentischen (3-Phenylpropan-1-ol) Komponenten
• – frei von als nachteilig diskutierten Wirkstoffen, wie z.B. Bronopol, Parabene, Isothiazolinone und Formaldehydabspalter
• – gute Wirksamkeit auch bei höheren pH-Werten (pH-Wert > 7)
• – enthaltenes 1,3-Propandiol weist neben einem Wirksamkeitsanteil auch hautfreundliche Eigenschaften auf

The concentrates according to the present invention are associated with the following advantages:

• - Good cold stability with high drug concentration
• - Liquid variant of 1,2-octanediol
• - Very good effectiveness at low use concentration
• - improved effectiveness compared to the individual components
• - Improved odor against an equal concentration of 3-phenylpropan-1-ol
• - Improved skin compatibility with respect to the required for equal effectiveness 1,2-octanediol concentration
• - Improved storage stability by addition of antioxidants possible, thereby avoiding any unwanted degradation products in topically applied products
• High proportion of natural (1,3-propanediol) or nature identical (3-phenylpropan-1-ol) components
• - Free from detrimentally discussed active ingredients such as bronopol, parabens, isothiazolinones and formaldehyde releaser
• - good effectiveness even at higher pH values (pH value> 7)
• - Contained 1,3-propanediol has in addition to a share of activity and skin-friendly properties

Advantages of 3-phenylpropan-1-ol:

• More stable in storage and less odorous than, for example, phenethyl alcohol
• - PH-level neutral
• - pH stable
• - Great heat and cold stability (in the heat, eg., When stored at 40 ° C, much lower tendency for oxidative decomposition than benzyl alcohol or phenethyl alcohol, due to the melting point, about -18 ° C, it tends to less quickly Crystallization as phenoxyethanol at approx. + 14 ° C)
• - good antimicrobial efficacy, especially in the fungicidal area
• - nature identical

Advantages of Octanediol-1,2:

• - good effectiveness, especially as a booster, especially in the fungicidal area
• - PH-level neutral
• - pH stable

Advantages of Propanediol-1,3:

• - nature identical
• - skin-friendly and moisturizing properties
• - Solubilizer
• - antimicrobial booster
• - Crystallization inhibitor

The advantages of the present invention will become apparent in particular from the examples. Percentages are by weight unless otherwise stated.

Examples

Example 1: Storage stability at low temperature

The following concentrates were formulated (Table 1): component Concentrate 1 /% by weight Concentrate 2 /% by weight 1,3-propanediol 20.0 30.0 Octanediol-1,2 30.0 25.0 3-phenylpropane-1-ol 50.0 45.0 Concentrate Concentrate 2 * is based on Concentrate 2 and also contains 100 ppm of Vitamin E as the only other ingredient.

The low-temperature stability of the concentrates 1, 2 and 2 * according to the invention was tested in a 30 ml screw-cap glass (see Tables 2 to 4): Concentrate 1 Concentrate 2 warehousing 24 hours 24 hours + 5 ° C clear clear -5 ° C clear clear Table 2: Short term cold stability test without seeding Concentrate 1 Concentrate 2 Concentrate 2 * null clear, colorless liquid clear, colorless liquid clear, colorless liquid 3 months clear, colorless liquid clear, colorless liquid clear, colorless liquid Table 3: Long-term cold stability test at -5 ° C without inoculation

Since octanediol-1,2 partially retarded crystallization occurs, the concentrates were inoculated in the cold (Table 4). Concentrate 1 Concentrate 2 warehousing 24 hours 48 hours 24 hours 48 hours + 5 ° C clear clear clear clear -5 ° C 1/3 of the concentrate crystallizes Concentrate completely crystallized Seed crystals still present, no further crystallization Seed crystals still present, no further crystallization Table 4: Short-term cold stability test with seeding

The cold stability tests show that the concentrate 1 according to the invention is stable on storage in the cold. Concentrate 2 has even better cold stability.

Example 2. Determination of the preservative effect (Koko test)

The test described below is carried out to determine the preservative effect in cosmetic formulations.

principle

With the help of the described method, the effectiveness of chemical preservatives with regard to the container preservation for cosmetic formulations should be checked. For this purpose, the preservatives to be examined are added in various concentrations to the unpreserved samples in various experimental approaches. Ongoing bacterial load is achieved by periodically inoculating the experimental approaches. In parallel with the inoculation, smears of the individual approaches are taken immediately before each. An assessment is made based on the microbial growth of the smears. A preservative is more effective the longer the time to first occurrence of microbial growth.

execution

In each case, 25 g of the cosmetic to be tested are weighed into wide-mouth bottles with screw cap (LDPE). The preservatives to be investigated are added in separate formulations in their application concentrations. In each case an unpreserved pattern serves as growth control. Two days after addition of the preservatives, the samples are infected with 0.1 ml of a vaccine solution consisting of the test organisms listed below. The vaccine has a titer of about 10 ⁸ -10 ⁹ germs / ml (Table 5). bacteria gram Positive Staphylococcus aureus ATCC 6538 Kocuria rhizophila ATCC 9341 gram Negative enterobacteria Enterobacter gergoviae ATCC 33028 Escherichia coli ATCC 11229 Klebsiella pneumoniae ATCC 4352 pseudomonas Pseudomonas aeruginosa ATCC 9027 Pseudomonas fluorescens ATCC 17397 Pseudomonas putida ATCC 12633 yeast Candida albicans ATCC 10231 Aspergillus brasiliensis ATCC 16404 molds Penicillium pinophilum ATCC 36839 Table 5

The kits are then streaked once a week on agar plates (Casein Peptone Soy Bleach Peptone Agar (CSA) for bacteria and Sabouraud Dextrose Agar (SA) for yeasts and molds) and then inoculated. The first smear (sterility test) is carried out both on uninhibited (TLSH) and on non-inhibited nutrient media in order to detect as much as possible of all initial contaminations. The microbial growth of the smears is assessed after a three-day incubation at 25 ° C. For safety reasons, negative smears are monitored and reassessed for another two days. The assessment of the preservative effect of the individual product concentrations is carried out in semi-quantitative method on the growth of the individual smears. - = free of vegetation ++ = moderate growth + = weak growth +++ = strong growth

Growth is differentiated by bacteria, yeasts and molds. The test is carried out for a maximum of six weeks, ie over six vaccination cycles, or stopped after multiple strong growth (+++).

Assessment of the results

The sample is well conserved according to criterion A if, under the laboratory conditions mentioned above, it has a period of six weeks without microbial attack of the sample batches, i. even after the sixth inoculation no microbial growth is detectable. Based on many years of experience with this test method, a microbiological stability recommended for cosmetics can be derived over 30 months.

If the sample shows weak microbial growth (+) during the six vaccination cycles, the sample meets criterion B. A B criterion can provide sufficient preservation if the microbiological risk analysis has control factors independent of the formulation. This could be z. Example, the use of a package with a pump instead of a can and / or high standards of Good Manufacturing Practice (GMP).

Results of the Koko test

Concentrates 2 and 2 * were tested in an O / W cream, the ingredients and amounts of which are listed in Table 6: Wt .-% Phase A (water phase) water 75.0 Glycerol (85%) 2.3 NaOH (45%) 0.2 Phase B (fat phase) Paraffin Liquidum 6.0 Dimethicone 5.0 stearic acid 4.0 cetyl alcohol 3.0 Glyceryl stearate / PEG 30 stearate 3.0 octyl palmitate 1.5 Table 6: Components of a test cream O / W

The ingredients of phase A were heated to 80 ° C. In a separate container, the ingredients of phase B were heated to 80 ° C. Then phase B was added with gentle mixing in phase A (400 min ^-1), and it was then homogenized. With stirring (about 300 min ^-1 ) was cooled to room temperature to obtain the O / W cream.

To this O / W cream (pH 5.5) were added different amounts of concentrates 2 and 2 * according to the invention. The results are shown in Table 7 below. pH beginning 1 W. 2 W. 3 W. 4 W. 5 W. 6 W. 1 blank value 5.5 --- +++ SHB +++ SHB ./. 2 1.0% concentrate 2 * 5.5 --- --- --- --- --- --- --- 3 1.0% concentrate 2 5.5 --- --- --- --- --- --- --- 4 1.5% concentrate 2 * 5.5 --- --- --- --- --- --- --- 5 1.5% concentrate 2 5.5 --- --- --- --- --- --- --- Table 7. W = week (s)

The results show that a typical cream is already preserved by concentrates according to the invention in an amount of 1.0% by weight.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• EP 0524548 A1 [0003]
• WO 2008/061187 A1 [0005]

Claims (9)

Liquid concentrate, that a) 20-70% by weight of 3-phenylpropan-1-ol, b) 10-50% by weight of octanediol-1,2, c) 15-60 wt .-% of 1,3-propanediol and d) optionally up to 2000 ppm of one or more antioxidants.  Concentrate according to Claim 1, characterized in that it comprises a) 30-60% by weight of 3-phenylpropan-1-ol, preferably 40-50% by weight, such as 45% by weight.  Concentrate according to Claim 1 or Claim 2, characterized in that it comprises b) 15 to 40% by weight of octanediol-1,2, preferably 20 to 30% by weight, such as 25% by weight.  Concentrate according to one of the preceding claims, characterized in that it comprises c) 20 to 45% by weight of 1,3-propanediol, preferably 25 to 35% by weight, such as 30% by weight.  Concentrate according to one of the preceding claims, characterized in that the antioxidant is selected from phenolic compounds (such as 3-tert-butyl-4-hydroxyanisole, 2,6-di-tert-butyl-p-cresol, dodecyl gallate, pyrogallate, tocopherol ) and its derivatives, preferably vitamin E and its derivatives, particularly preferably vitamin E.  Concentrate according to one of the preceding claims, characterized in that the amount of antioxidant is 20 to 400 ppm, preferably 50 to 300 ppm, in particular 80 to 200 ppm, such as 100 ppm.  Concentrate according to one of the preceding claims, characterized in that it consists of the constituents a) to c) and optionally d).  An antimicrobial finished product for topical application comprising from 0.2% to 3.0% by weight of the concentrate according to any one of the preceding claims, preferably from 0.3% to 2.0%, more preferably from 0.5% to 1.5% wt .-%  Product according to claim 8, characterized in that it is a cream.