Glycolipid composition and application thereof in cosmetics

Abstract

The invention provides a glycolipid composition and application thereof in cosmetics. The composition is prepared from 10 to 40 parts of rhamnolipid and 0.1 to 10 parts of polypeptide active matters. The invention also provides application of the composition and a cosmetic composition prepared from the composition. The composition provided by the invention can balance permeability, emulsibility and wettability so as to penetrate into the skin and promote the absorption of active matters, is very suitable for promoting the absorption of the active matters in cosmetics, and is suitable for large-scale production and application.

Description

Technical Field

[0001] The invention belongs to the field of rhamnolipids, and particularly relates to a glycolipid composition and application thereof in cosmetics. Background Art

[0002] Peptide active ingredients are compounds formed by the condensation of 2 to 100 amino acids through peptide bonds. They are biologically active substances that participate in various cell functions in organisms, and deeply participate in and regulate the functional activities of various systems, organs and cells in the human body. Peptides are rich in variety and have physiological activity. They can promote the proliferation of skin tissue cells, collagen synthesis and secretion, tissue repair and regeneration, etc. They are effective in solving wrinkles, aging and dull skin, so they have become one of the ingredients added to cosmetics. However, there are two technical difficulties in the application of peptides. One is that the molecular weight of peptide active ingredients is large, and it is difficult to pass through the skin barrier and enter the cell to play a role. Second, peptides are greatly affected by the temperature, pH value, ion concentration and redox state of the system during use. Under unsuitable conditions, peptides may undergo irreversible changes such as unfolding, aggregation, degradation or loss of activity.

[0003] Since large molecular weight products have great difficulty in penetrating the skin, most peptides are currently difficult to be absorbed by the skin, enter the cells and exert their effects. Therefore, there is an urgent need to develop a composition suitable for promoting the absorption of peptides. Summary of the invention

[0004] In order to make up for the deficiencies in the prior art, an object of the present invention is to provide a rhamnolipid composition for promoting polypeptide absorption, which can also be understood as a polypeptide composition. By formulating a specific rhamnolipid, the resulting composition can penetrate the skin barrier and transport the polypeptide into the cell to exert its effect. It is particularly suitable for cosmetics containing polypeptides. At the same time, rhamnolipid is very mild and will not cause polypeptide denaturation, and has strong industrial applicability.

[0005] Rhamnolipid is a biological surfactant with biological metabolic properties produced by Pseudomonas or Burkholderia. The structure of rhamnolipid usually contains a hydrophilic part composed of 1-2 molecules of rhamnose ring (sugar group) and a hydrophobic part composed of 1-2 molecules of saturated or unsaturated fatty acids (lipid part) of different carbon chain lengths. Rhamnolipid has been widely used in many cleaning fields such as industry and civil use as a simple and environmentally friendly biosurfactant. The inventors found that Pseudomonas or Burkholderia take in hydrophobic substrates in the natural environment through rhamnolipids, and absorb them as nutrients after passing through the cell membrane. The inventors believe that this shows that rhamnolipid has good cell membrane permeability. At the same time, rhamnolipid is very mild, and a large number of hydroxyl groups on the molecule can form hydrogen bonds with amino groups, which can improve the stability of amino-containing compounds.

[0006] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solution:

[0007] A rhamnolipid composition comprises, by weight, 10 to 40 parts of rhamnolipid and 0.1 to 10 parts of polypeptide active substances.

[0008] Rhamnolipids have good cell membrane permeability, and their structure is similar to that of a phospholipid bilayer, which is extremely low in skin irritation. Moreover, rhamnolipids can be completely degraded in nature, which is in line with current environmental protection concepts. The inventors have found that for polypeptide penetration, rhamnolipids are not only required to have certain permeability and hydrophilicity to the cell membrane, but also must not cause protein denaturation and affect the function of polypeptides. Therefore, rhamnolipid compositions can have the advantages of promoting polypeptide penetration and low skin irritation, and are therefore very suitable for cosmetics containing polypeptides.

[0009] The rhamnolipid of the present invention can be a mixture obtained by compounding various types of rhamnolipid pure products, or it can be a concentrated fermentation broth produced by fermentation. In some preferred embodiments, the rhamnolipid composition is a concentrated fermentation broth produced by fermentation of Pseudomonas aeruginosa, and the fermentation method can be a commonly used method in the art.

[0010] As is known in the art, the rhamnolipid is rhamnolipid and / or a salt of rhamnolipid, wherein the salt of rhamnolipid includes an inorganic salt of rhamnolipid and / or an organic salt of rhamnolipid; preferably, the inorganic salt includes but is not limited to K + 、Na + Mg 2+ , Ca 2+ 、Al 3+ One or more of metal salts; organic salts include but are not limited to NH 4+ One or more of the salts formed by primary amines, secondary amines, tertiary amines and rhamnolipids.

[0011] In one embodiment of the present invention, the rhamnolipid composition comprises 1 to 40 parts of Rha-C10C10 type rhamnolipid and 35 to 99 parts of RhaRha-C10C10 type rhamnolipid by weight, preferably the rhamnolipid composition comprises 10 to 40 parts of Rha-C10C10 type rhamnolipid and 35 to 85 parts of RhaRha-C10C10 type rhamnolipid. The Rha-C10C10 type and RhaRha-C10C10 type rhamnolipids of the present invention have a common structure in the art, and their structural formula is as follows (wherein Rha represents a sugar ring):

[0012]

[0013] In one embodiment of the present invention, the rhamnolipid composition further comprises, by weight, one or more of the following rhamnolipid types: 0.1 to 10 parts of RhaRha-C8C10 type, 0.1 to 2 parts of Rha-C8C10 type, 0.5 to 20 parts of RhaRha-C10C12 type, 0.1 to 10 parts of RhaRha-C10C12:1 type, 0.1 to 5 parts of Rha-C10C12 type, 0.1 to 5 parts of Rha-C10C12: 2:1 type; preferably, by weight, the rhamnolipid composition further comprises one or more of the following rhamnolipid types: 0.2-5 parts of RhaRha-C8C10 type, 0.3-1 parts of Rha-C8C10 type, 5-10 parts of RhaRha-C10C12 type, 0.2-5 parts of RhaRha-C10C12:1 type, 0.2-2.5 parts of Rha-C10C12 type, 0.2-2.5 parts of Rha-C10C12:1 type. The above structure is the conventional structure type and content of rhamnolipid.

[0014] In one embodiment of the present invention, the polypeptide active substance in the rhamnolipid composition comprises one or more of neurotransmitter inhibitory peptides, carrier peptides, and signal peptides; preferably, the polypeptide active substance is selected from one or more of acetyl hexapeptide, acetyl octapeptide, red scorpion toxin, snake venom peptide, cyclic peptide, copper peptide, carnosine, and palmitic acid tetrapeptide. The polypeptide active substances are commonly used active substances in the field of cosmetics, and they can obtain similar penetration-promoting effects when combined with rhamnolipid.

[0015] Another object of the present invention is to provide a use of a rhamnolipid composition.

[0016] A use of a rhamnolipid composition, wherein the composition is the above-mentioned rhamnolipid composition, and the composition is used in cosmetics, preferably in skin care products, and more preferably in water, lotion, cream, and facial mask.

[0017] Another object of the present invention is to provide a cosmetic composition.

[0018] A cosmetic composition comprising the above-mentioned rhamnolipid composition.

[0019] In one embodiment of the present invention, the cosmetic composition comprises, by weight: 0.1 to 5 parts of the rhamnolipid composition, 0 to 1 parts of a thickener, 0 to 0.5 parts of a pH adjuster, 1 to 8 parts of a moisturizer, 0 to 2 parts of an emulsifier, and 0 to 2 parts of a preservative.

[0020] In one embodiment of the present invention, the thickener comprises one or more of acrylic acid copolymer, acrylamide copolymer, ester, natural high molecular polymer, preferably one or more of carbomer, ammonium acryloyldimethyltaurate / VP copolymer, PEG-120 methyl glucose dioleate, xanthan gum, and cellulose. The above raw materials are commonly used substances in the cosmetic field.

[0021] In one embodiment of the present invention, the pH regulator is one or more of an organic acid, an inorganic acid, an organic base, an inorganic base, preferably one or more of citric acid, malic acid, lactic acid, sodium hydroxide, potassium hydroxide, and glutamic acid. The above raw materials are commonly used substances in the cosmetic field.

[0022] In one embodiment of the present invention, the humectant is a polyglycerol humectant and / or a diol humectant, preferably one or more of glycerol and its derivatives, propylene glycol, butylene glycol, panthenol, polyethylene glycol and its derivatives. The above raw materials are commonly used substances in the cosmetic field.

[0023] In one embodiment of the present invention, the emulsifier is one or more of polymeric polyol emulsifiers, synthetic ester emulsifiers, and natural phospholipid emulsifiers, preferably one or more of polyethylene glycols, glycerides, sugar derivatives, and phospholipids. The above raw materials are commonly used substances in the cosmetic field.

[0024] In one embodiment of the present invention, the preservative is one or more of a polyol preservative, a ketone preservative, and an organic acid preservative, preferably one or more of phenoxyethanol, caprylyl glycol, pentylene glycol, hexylene glycol, p-hydroxyacetophenone, and caprylhydroxamic acid. The above raw materials are commonly used in the field of cosmetics.

[0025] The cosmetics provided by the present invention can be prepared using a common preparation process in the art, for example, by adding the various ingredients into water in any order to achieve a desired weight percentage range.

[0026] Compared with the prior art, the technical solution provided by the present invention has the following advantages:

[0027] (1) The composition can balance permeability and hydrophilicity. Adding polypeptide active ingredients therein can form hydrogen bonds with the amino groups on the polypeptide, making the polypeptide more stable. At the same time, after passing through the cell membrane, it can be metabolized by the cell, allowing the polypeptide to exert its effect at a higher level. Therefore, the rhamnolipid composition of the present invention has strong transdermal permeability, low irritation, and promotes polypeptide absorption, and is therefore very suitable for the cosmetics field.

[0028] (2) The preparation process is simple, the product is cheap and readily available, and a variety of products with different properties can be obtained by adjusting the proportion of the components of the composition. The product has a wide range of applications. Moreover, rhamnolipid is a biodegradable substance and is environmentally friendly.

[0029] (3) It has excellent skin permeability. Compared with directly adding peptides to the formula, the effect is greatly improved. Therefore, it has very broad application potential in the cosmetics field and is suitable for large-scale production and application. DETAILED DESCRIPTION

[0030] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments.

[0031] The percentages used in the embodiments and comparative examples of the present invention are all mass percentages unless otherwise specified.

[0032] The raw materials or reagents used in the examples and comparative examples of the present invention are shown in the following table. Other raw materials or reagents are commercially available unless otherwise specified.

[0033]

[0034]

[0035] Among them, rhamnolipid refers to the concentrated fermentation broth produced by Pseudomonas aeruginosa fermentation, and its conventional preparation process is as follows:

[0036] Rhamnolipid fermentation broth: first, Pseudomonas aeruginosa was inoculated on a solid culture medium by a plate streaking method to activate the strain; then, a single colony was picked from the activated strain and inoculated into a seed culture medium (composition includes: peptone 10.0 g / L, yeast powder 5.0 g / L, NaCl 10.0 g / L), and cultured at 30°C for 6 hours to obtain a seed solution; then, the seed solution was inoculated into a fermentation medium (composition includes: yeast extract 5 g / L, urea 5 g / L, sodium nitrate 10 g / L, Na 2 HPO 4 4g / L, KH 2 PO 4 4g / L, CaCl 2 0.4g / L, MgSO 4 2g / L) to obtain rhamnolipid fermentation broth.

[0037] Separation and purification: The rhamnolipid fermentation liquid was centrifuged at 6000rpm for 15min, the supernatant was collected and 38wt% concentrated hydrochloric acid was added thereto to adjust the pH to 1.5-2.0, and then the mixture was placed in a 4°C refrigerator for 24h, and centrifuged again at 6000rpm for 10min to collect the precipitate; the precipitate was mixed with 3 times the volume of methanol, filtered with a 30000Da ultrafiltration membrane, the filtrate was collected, and then the methanol was evaporated at 70°C for 3h using a rotary evaporator to obtain a paste; the paste was mixed with the same volume of water, and then the pH was adjusted to above 6.0 with a 3M sodium hydroxide aqueous solution, stirred and dissolved for 2h, pre-frozen at -80°C for 3h, and then placed in a freeze dryer at -86°C for freeze drying for 48h to obtain rhamnolipid.

[0038] By using the same method as above, fermentation broths with different components were obtained by adjusting the fermentation and separation and purification process parameters. The specific components (quantified by HPLC) were shown in the examples and comparative examples.

[0039] The preparation method of the rhamnolipid composition is as follows:

[0040] Mix the rhamnolipid solution with acetyl hexapeptide-38 or blue copper peptide or cyclic peptide in a certain proportion and stir until completely dissolved.

[0041] Example 1

[0042] The composition of rhamnolipids is as follows:

[0043] Rhamnolipid ingredients Ratio (wt.%) RhaRha-C8C10 2.8 Rha-C8C10 0.72 RhaRha-C10C10 69.68 Rha-C10C10 12.8 RhaRha-C10C12 7.6 RhaRha-C10C12:1 3.1 Rha-C10C12 1.9 Rha-C10C12:1 1.4

[0044] The rhamnolipid of Example 1 was named "rhamnolipid-1", and rhamnolipid-1 was used to construct the compositions of rhamnolipid and polypeptide.

[0045] The formula of Example 1-1 is as follows:

[0046]

[0047]

[0048] The formula of Example 1-2 is as follows:

[0049] composition Weight Rhamnolipid-1 20 Acetyl Hexapeptide-38 0.2

[0050] The formula of Examples 1-3 is as follows:

[0051] composition Weight Rhamnolipid-1 30 Blue Copper Peptide 0.6

[0052] Example 2

[0053] The composition of rhamnolipids is as follows:

[0054] Rhamnolipid ingredients Ratio (wt.%) RhaRha-C8C10 2.3 Rha-C8C10 0.68 RhaRha-C10C10 52.82 Rha-C10C10 30.5 RhaRha-C10C12 8.2 RhaRha-C10C12:1 2.7 Rha-C10C12 1.6 Rha-C10C12:1 1.2

[0055] The rhamnolipid of Example 2 was named "rhamnolipid-2", and rhamnolipid-2 was used to construct a composition of rhamnolipid and polypeptide.

[0056] The formula of Example 2-1 is as follows:

[0057] composition Weight Rhamnolipid-2 30 Acetyl Hexapeptide-38 0.6

[0058] The formula of Example 2-2 is as follows:

[0059] composition Weight Rhamnolipid-2 10 Acetyl Hexapeptide-38 0.5

[0060] The formula of Example 2-3 is as follows:

[0061] composition Weight Rhamnolipid-2 30 Cyclic peptides 0.6

[0062] Example 3

[0063] The composition of rhamnolipids is as follows:

[0064]

[0065]

[0066] The rhamnolipid of Example 3 was named "rhamnolipid-3", and rhamnolipid-3 was used to construct the compositions of rhamnolipid and polypeptide.

[0067] The formula of Example 3-1 is as follows:

[0068] composition Weight Rhamnolipid-3 15 Acetyl Hexapeptide-38 1.5

[0069] The formula of Example 3-2 is as follows:

[0070] composition Weight Rhamnolipid-3 20 Acetyl Hexapeptide-38 3

[0071] Example 4

[0072] The composition of rhamnolipids is as follows:

[0073]

[0074]

[0075] The rhamnolipid of Example 4 was named "rhamnolipid-4", and rhamnolipid-4 was used to construct the compositions of rhamnolipid and polypeptide, respectively.

[0076] The formula of Example 4-1 is as follows:

[0077] composition Weight Rhamnolipid-4 10 Acetyl Hexapeptide-38 2

[0078] The formula of Example 4-2 is as follows:

[0079] composition Weight Rhamnolipid-4 30 Acetyl Octapeptide-3 7.5

[0080] Comparative Example 1

[0081] Compared with Example 2-1, acetyl hexapeptide-38 was used alone at 0.6%.

[0082] Comparative Example 2

[0083] Compared with Example 1-3, 0.6% of blue copper peptide was used alone.

[0084] Comparative Example 3

[0085] Compared with Example 2-3, the cyclic peptide was used alone at 0.6%.

[0086] Test Example 1: Skin Permeability

[0087] The ex vivo pig skin was fixed between the drug administration pool and the receiving pool using a Franz diffusion apparatus. The effective penetration area of ​​the diffusion pool was 2.8 cm 2 , the stratum corneum faces the supply chamber, and the dermis faces the receiving chamber. Weigh the rhamnolipid composition containing acetyl hexapeptide-38, place it in the dosing pool, and apply it evenly on the ex vivo pig skin of the same size. Fix the upper and lower chambers, keep stirring at a constant temperature of 37±0.5℃, and take the receiving solution after 0.5, 3, 6, and 12 hours, respectively, and replenish the receiving solution of the same temperature and volume at the same time. Centrifuge the receiving solution, take the supernatant and filter it with a microporous filter membrane, and use liquid chromatography-tandem mass spectrometry to detect the concentration of the polypeptide in the filtrate, and calculate the cumulative permeation per unit area Q.

[0088] Cumulative infiltration per unit area

[0089] Where Cn is the concentration measured at the nth sampling point; V is the volume of the receiving pool; and S is the effective diffusion area.

[0090] Cumulative permeability per unit area K = [Q / m] × 100%

[0091] Here, m is the amount of acetyl hexapeptide-38 / blue copper peptide / cyclic peptide, etc. in 1 g of the rhamnolipid-containing composition.

[0092] The results are shown in Table 1.

[0093] Table 1 Cumulative permeability per unit area

[0094]

[0095]

[0096] The rhamnolipid compositions containing acetyl hexapeptide-38 / blue copper peptide / cyclic peptide etc. prepared in Examples 1-4 of the present invention have a significant effect of promoting transdermal absorption compared to the use of acetyl hexapeptide-38 / blue copper peptide / cyclic peptide etc. alone.

[0097] Test Example 2 Cosmetics containing rhamnolipid composition

[0098] The rhamnolipid composition was prepared into a cosmetic composition, and the anti-aging effect of the cosmetic was evaluated by human experiments using essence water as an example. The cosmetic formula is shown in Table 2:

[0099] Table 2 Essence formula

[0100]

[0101] The preparation process is as follows:

[0102] 1. Add phase A to the main pot, heat to 85 degrees, and stir to disperse evenly;

[0103] 2. Cool down to 45 degrees, add phase B, phase C and phase D into the main pot in turn, and stir at low speed until completely uniform.

[0104] The rhamnolipid composition or acetyl hexapeptide-38 is added to the formula at an amount of 500 ppm of acetyl hexapeptide-38, and the rest is made up with water.

[0105] Table 3 Essence formula 2

[0106]

[0107] The preparation process is as follows:

[0108] 1. Add phase A to the main pot, heat to 85 degrees, and stir to disperse evenly;

[0109] 2. Cool down to 45 degrees, add phase B, phase C and phase D into the main pot in turn, and stir at low speed until completely uniform.

[0110] Among them, the rhamnolipid composition or blue copper peptide is added to the formula at a blue copper peptide addition amount of 100 ppm, and the rest is made up with water.

[0111] According to the cosmetics industry standards, a double-blind randomized half-face experiment was used to evaluate the human efficacy. A multifunctional skin tester was used to measure the skin condition parameters (including skin elasticity and skin moisture content) of volunteers before use (day 0) and after use (week 1, week 2, and week 3) to test whether there was anti-aging effect. The formula in Table 2 was used for testing.

[0112] Usage: Apply an appropriate amount of the product to the face, gently apply until absorbed, use once in the morning and evening, use for 3 consecutive weeks, and conduct efficacy evaluation tests every Monday morning. In the double-blind half-face experiment, the skin elasticity test and skin moisture test were performed using a multifunctional skin tester invented by the German CK company.

[0113]

[0114] The test results are shown in Table 3:

[0115] It can be seen from the results in Table 3 that the use of the rhamnolipid composition of the present invention to promote penetration has better skin elasticity and moisturizing properties than the use of acetyl hexapeptide-38 alone. At the same time, when the rhamnolipid content is high, the penetration effect will be improved. As the polypeptide content continues to increase, the penetration effect will decrease slightly. It is possible that when the polypeptide content is high, the micelle size will increase, which will reduce the ability to penetrate the skin.

[0116] Unless otherwise defined, the terms used in the present invention have the meanings commonly understood by those skilled in the art.

[0117] The embodiments described in the present invention are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. Those skilled in the art may make various other substitutions, changes and improvements within the scope of the present invention. Therefore, the present invention is not limited to the above embodiments, but is only limited by the claims.

Claims

1. A rhamnolipid composition, It is characterized in that In parts by weight, the composition comprises 10 to 40 parts of rhamnolipid and 0.1 to 10 parts of polypeptide active substance.

2. The rhamnolipid composition according to claim 1, It is characterized in that The rhamnolipid is a concentrated fermentation liquid produced by fermentation of Pseudomonas aeruginosa.

3. The rhamnolipid composition according to claim 1 or 2, It is characterized in that In parts by weight, the rhamnolipid composition comprises 1 to 40 parts of Rha-C10C10 rhamnolipid and 35 to 99 parts of RhaRha-C10C10 rhamnolipid, and preferably the rhamnolipid composition comprises 10 to 40 parts of Rha-C10C10 rhamnolipid and 35 to 85 parts of RhaRha-C10C10 rhamnolipid.

4. The rhamnolipid composition according to any one of claims 1 to 3, It is characterized in that The rhamnolipid composition further comprises one or more of the following rhamnolipid types by weight: 0.1 to 10 parts of RhaRha-C8C10 type, 0.1 to 2 parts of Rha-C8C10 type, 0.5 to 20 parts of RhaRha-C10C12 type, 0.1 to 10 parts of RhaRha-C10C12:1 type, 0.1 to 5 parts of Rha-C10C12 type, and 0.1 to 5 parts of Rha-C10C12:1 type; Preferably, the rhamnolipid composition further comprises one or more of the following rhamnolipid types, measured by weight: 0.2 to 5 parts of RhaRha-C8C10 type, 0.3 to 1 parts of Rha-C8C10 type, 5 to 10 parts of RhaRha-C10C12 type, 0.2 to 5 parts of RhaRha-C10C12:1 type, 0.2 to 2.5 parts of Rha-C10C12 type, and 0.2 to 2.5 parts of Rha-C10C12:1 type.

5. The rhamnolipid composition according to any one of claims 1 to 4, It is characterized in that The polypeptide active substance in the rhamnolipid composition comprises one or more of a neurotransmitter inhibitory peptide, a carrier peptide, and a signal peptide; Preferably, the polypeptide active ingredient is selected from one or more of acetyl hexapeptide, acetyl octapeptide, red scorpion toxin, snake venom peptide, cyclic peptide, copper peptide, carnosine, and palmitic acid tetrapeptide.

6. Use of a rhamnolipid composition, wherein the composition is the rhamnolipid composition according to any one of claims 1 to 5, and the composition is used in cosmetics, preferably in skin care products, and more preferably in water, lotion, cream, and facial mask.

7. A cosmetic composition comprising the rhamnolipid composition according to any one of claims 1 to 5.

8. The cosmetic composition according to claim 7, It is characterized in that The cosmetic composition comprises, by weight: 0.1 to 5 parts of the rhamnolipid composition, 0 to 1 part of a thickener, 0 to 0.5 parts of a pH adjuster, 1 to 8 parts of a moisturizer, 0 to 2 parts of an emulsifier, and 0 to 2 parts of a preservative.

9. The cosmetic composition according to claim 6 or 7, It is characterized in that The thickener comprises one or more of acrylic acid copolymer, acrylamide copolymer, ester, natural high molecular polymer, preferably one or more of carbomer, ammonium acryloyldimethyltaurate / VP copolymer, PEG-120 methyl glucose dioleate, xanthan gum, and cellulose; and / or, the pH regulator is one or more of an organic acid, an inorganic acid, an organic base, an inorganic base, preferably one or more of citric acid, malic acid, lactic acid, sodium hydroxide, potassium hydroxide, and glutamic acid; and / or, the humectant is a polyglycerol humectant and / or a diol humectant, preferably one or more of glycerol and its derivatives, propylene glycol, butylene glycol, panthenol, polyethylene glycol and its derivatives; And / or, the emulsifier is one or more of polymeric polyol emulsifiers, synthetic ester emulsifiers, and natural phospholipid emulsifiers, preferably one or more of polyethylene glycols, glycerides, sugar derivatives, and phospholipids; And / or, the preservative is one or more of a polyol preservative, a ketone preservative, and an organic acid preservative, preferably one or more of phenoxyethanol, caprylyl glycol, pentylene glycol, hexylene glycol, p-hydroxyacetophenone, and caprylhydroxamic acid.

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