FI129488B

FI129488B - Salve composition, method of manufacture and use of the composition

Info

Publication number: FI129488B
Application number: FI20205427A
Authority: FI
Inventors: Kari Holopainen
Original assignee: Nordic Biotech Group Oy
Priority date: 2020-04-28
Filing date: 2020-04-28
Publication date: 2022-03-15
Also published as: FI20205427A1; WO2021219939A1

Abstract

The disclosure relates to a method for manufacturing a salve composition comprising coniferous resin acids (82), wherein the method comprises providing a resin acid fraction (10); dissolving the resin acid fraction (10) into ethanol (20), wherein the resin acid fraction (10) comprises at least 70 wt-% of resin acids of which 4 - 10 wt-% of palustric acid to provide a resin solution (30); concentrating the obtained resin solution (30) to provide a concentrated resin solution (40); providing a hydrogenated (50) and/or a partially hydrogenated vegetable oil (51), and a non-hydrogenated vegetable oil; mixing the hydrogenated (50) and/or partially hydrogenated vegetable oil (51) with the non-hydrogenated vegetable oil (60) to form an oil base (70); mixing the concentrated resin solution (40) with the oil base (70) to provide a resin-oil mixture (80); and wherein an antioxidant(s) (90) is added to the resin solution (30), or to the resin-oil mixture (80), and that the amount of added antioxidant(s) (90) is from 0.005 to 0.15 % (w/w) of the total composition. The disclosure further relates to a salve composition comprising coniferous resin acids and to use of said composition in a method for treating skin diseases in humans and animals.

Description

SALVE COMPOSITION, METHOD OF MANUFACTURE AND USE OF THE COMPOSITION

FIELD OF THE DISCLOSURE The present disclosure relates to a salve composition, and more particularly to a salve composition comprising coniferous resin acids. The present disclosure further concerns the manufacturing method of a salve composition comprising coniferous resin acids and its use in methods for the treatment of skin disorders in humans and animals.

BACKGROUND OF THE DISCLOSURE Salves manufactured from the Norway spruce (Picea abies) have been utilized for centuries in folk-medicine. Such salves are traditionally manufactured by boiling the resin with butter or animal fat. Coniferous resin is known to be poorly soluble and solid at room temperature, and therefore high temperatures have typically been utilized to enhance the solubility of the resin into fat bases.

Coniferous resin acids form hydroxylated derivatives upon oxidation reactions. The abietic type resin acids are more prone to oxidation due to the conjugated double bonds, and the auto-oxidation and oxidation is usually started by the initiation step i.e. by the effect of oxygen, heat, UV-radiation, shear stress or impurities, free radicals are formed that accelerate the degradation. Just like fatty acids, resin acids with no double bonds, such as dehydroabietic acid, have higher oxidative stability. Further, it has been found that air and light -exposed Portuguese gum rosin (PGR) shows a decrease in resin acids such as abietic, neoabietic, levopimaric and palustric, and this is probably secondary to autoxidation.

Colophony (rosin/resin) is known to cause allergy. It is a complex mixture of over 100 N 25 compounds derived from pine trees. The principle allergens in colophony are the oxidation N products of unmodified and modified colophony and some of the new resin acids S synthesized during modification. Amongst the oxidation products of colophony that are = thought to cause the allergenic effects are for example the following: 15- = hydroperoxyabietic acid, 15-hydroperoxydehydroabietic acid, 13,14-alpha-epoxyabietic N 30 acid, 13,14-beta-epoxyabietic — acid, 15-hydroxydehydroabietic acid, 15-hydroxy-7- s oxodehydroabietic acid, 7-oxodehydroabietic acid, 8,12-peroxidoA!3:14-dihydroabietic acid, N 12-alpha-hydroxyabietic acid, di(methyl dehydroabietate-15-yl) peroxide, pentaerythritol N esterified gum rosin, maleopimaric acid, fumaropimaric acid, and the neutral fraction of gum rosin. In addition to resin acids, colophony (resin/rosin) contains monoterpenes, such as a -pinene, B -pinene and limonene which also may cause allergic reactions upon oxidation.

Document US2018000095A discloses an oil-in-water dispersion comprising coniferous resin acids, its preparation and use as an antimicrobial and anti-inflammatory agent in medical and non-medical products.

The invention also relates to a pharmaceutical product comprising the oil-in-water dispersion.

Coniferous resin acids in said composition include dehydroabietic acid, 7-beta-hydroxydehydroabietic acid, 7-alpha-hydroxydehydroabietic acid, 15-hydroxydehydroabietic acid, 7-beta, 15-dihydroxydehydroabietic acid, 7-alpha,15- dihydroxydehydroabietic acid, 18-hydroxydehydroabietic acid, further hydroxylated derivates of dehydroabietic acid or a mixture thereof.

Document EP2775838B discloses an aqueous antimicrobial composition including coniferous resin acids, a dispersing agent and an aqueous medium, a method for its preparation and its use as an antimicrobial agent in medical and non-medical field.

Said aqueous antimicrobial composition comprises coniferous resin acids, a dispersing agent and an aqueous medium, wherein an amount of the coniferous resin acids of the composition is in the range of 1 to 100 ppm, the coniferous resin acids comprise 7a- hydroxydehydroabietic acid, 7a-hydroxydehydroabietic acid, 15-hydroxydehydroabietic acid, 7B,15-dihydroxy-dehydroabietic acid, 7a,15-dihydroxydehydroabietic acid, 18- hydroxydehydroabietic acid, further hydroxylated derivates of dehydroabietic acid or a mixture thereof, and said composition can be used for example as an antimicrobial additive in cosmetics.

Document US2017368123AA discloses an anti-inflammatory agent comprising water soluble coniferous resin acids for use in treating or preventing sterile inflammation in human or animal tissue, and a pharmaceutical formulation comprising an anti- inflammatory agent comprising water soluble coniferous resin acids for use in treating or N preventing sterile inflammation in human or animal tissue. "Coniferous resin acid" refers N to organic acids found in resin and/or rosin, such as hydroxylated derivates of 7 hydroxydehydroabietic acid.

In one embodiment the coniferous resin acids are selected from the group consisting of dehydroabietic acid, 7-beta-hydroxydehydroabietic acid, 7- E 30 alpha-hydroxydehydroabietic — acid, — 15-hydroxydehydroabietic — acid, 7-beta,15- N dihydroxydehydroabietic acid, 7-alpha,15-dihydroxydehydroabietic acid, 18- 3 hydroxydehydroabietic acid, further hydroxylated derivates of dehydroabietic acid and a O mixture thereof.

A problem with the previously described documents is that the compositions contain hydroxylated derivatives of resin acids, i.e. oxidation products of coniferous resin acids.

As previously explained said hydroxylated derivatives are known to cause allergic reactions and other adverse effects. Therefore, there exist a need for stable and well tolerated compositions whereby allergic reactions can be avoided or at least minimised.

REFERENCES Downs A. M. R. and Samson J. E. Colophony allergy: a review. Contact Dermatitis 1999(41):305-310. Fan Ren et al. 2015. Thermal oxidation reaction process and oxidation kinetics of abietic acid. The Royal Society of Chemistry, 2015(5):17123.

BRIEF DESCRIPTION OF THE DISCLOSURE An object of the present disclosure is to provide a method and a composition so as to alleviate the above disadvantages of the compositions comprising coniferous resin acids. The object of the disclosure is achieved by a method, a composition, and use of the composition which are characterized by what is stated in the independent claims. The preferred embodiments of the disclosure are disclosed in the dependent claims. The thus obtained composition is stable during manufacturing and upon storage at various temperatures. Although unoxidized pure abietic acid is not allergenic, rosin s (Colophony) are unstable against air, heat and light. Rosin's instability to oxidation and photo-oxidation and N corresponding darkening is primarily concerned with conjugated double bonds of abietic N type resin acids. Rosin auto-oxidation and oxidation is started by the initiation step (i.e.

QA > 25 oxygen, heat, UV-radiation, shear stress or impurities), wherein free radicals are formed = that accelerate the degradation. The oxidation of abietic acid takes place in two stages, in E the first step, peroxide is formed, followed by further oxidation, which forms hydroxyl- N containing abietic acid oxide. + O The invention is directed to a method of manufacturing a salve composition comprising O 30 coniferous resin acids, wherein the method comprises providing resin/rosin as resin acid fraction; dissolving the resin acid fraction into ethanol, wherein the resin acid fraction comprises at least 70 wt-% of resin acids of which 4-10 wt-%, preferably 6 — 8 wt-% of palustric acid, and = 20 wt-% of abietic acid to provide a resin solution; concentrating the obtained resin solution to provide a concentrated resin solution; providing a hydrogenated vegetable oil and/or a partially hydrogenated vegetable oil, and a non-hydrogenated vegetable oil; mixing the hydrogenated and/or partially hydrogenated vegetable oil with the non-hydrogenated vegetable oil to form an oil base; mixing the concentrated resin solution with the oil base to provide a resin-oil mixture; and wherein an antioxidant(s) is added to the resin solution, or to the resin-oil mixture, and that the amount of added antioxidant(s) is from 0.005 to 0.15 % (w/w), preferably from 0.01 to 0.1 % (w/w), more preferably from

0.04 to 0.06 % (w/w) of the total composition. The invention is directed to a salve/ointment composition comprising coniferous resin acids, vegetable oil base and an antioxidant(s). Moreover, the invention is directed to use of the salve/ointment composition in a method for the treatment of skin disorders in humans and animals. An advantage of the method and the composition of the disclosure is that by the new manufacturing method oxidation can be reduced. When determining the amount of abietic acid, it was noticed that the amount of abietic acid versus theoretical value decreased clearly in the samples manufactured without an antioxidant. Surprisingly, it was found that by adding an antioxidant according to the method of the disclosure the oxidation can be significantly reduced, and the product does not need to be kept in a cool place. The composition can be used and stored in countries with warm climates. Moreover, the composition tolerates momentary freezing, and it can also be stored and used in cold climates if needed.

BRIEF DESCRIPTION OF THE DRAWINGS In the following the disclosure will be described in greater detail by means of preferred N 25 embodiments with reference to the accompanying drawings, in which it is presented the N method for manufacturing of a salve composition comprising coniferous resin acids. S Figure 1 is a schematic flow diagram representing one embodiment of the method; wherein = an antioxidant(s) is added to the resin solution at the beginning of the manufacturing E process. N 30 Figure 2 illustrates a schematic flow diagram representing a further embodiment of the 2 method, wherein an antioxidant(s) is added to the resin-oil mixture at the end of the O manufacturing process.

DETAILED DESCRIPTION OF THE DISCLOSURE The disclosure relates to a method of manufacturing a salve composition comprising coniferous resin acids, wherein the method comprises providing resin/rosin as resin acid fraction; dissolving the resin acid fraction into ethanol, wherein the resin acid fraction 5 comprises at least 70 wt-% of resin acids of which 4-10 wt-%, preferably 6 — 8 wt-% of palustric acid, and = 20 wt-% of abietic acid, to provide a resin solution; concentrating the obtained resin solution to provide a concentrated resin solution; providing a hydrogenated and/or partially hydrogenated vegetable oil and a non-hydrogenated vegetable oil; mixing the hydrogenated vegetable with the non-hydrogenated vegetable oil to form an oil base; mixing the concentrated resin solution with the oil base to provide a resin-oil mixture; and wherein antioxidant, such as butyl hydroxy anisole (BHA), is added to the resin solution, and/or to the resin-oil mixture, and that the amount of added antioxidant(s) is typically from

0.005 to 0.15 % (w/w), preferably from 0.01 to 0.1 % (w/w), more preferably from 0.04 to

0.06 % (w/w) of the total composition.

The disclosure relates also to a salve composition obtainable by the method according to the invention. Further, the disclosure relates to use of the salve composition obtainable by the method of the invention.

In an embodiment, the salve composition comprising coniferous resin acids is obtained by the method for manufacturing a salve composition comprising coniferous resin acids, wherein the method comprises providing a resin acid fraction; dissolving the resin acid fraction into ethanol, wherein the resin acid fraction comprises at least 70 wt-% of resin acids of which 4-10 wt-%, preferably 6 — 8 wt-% of palustric acid, and = 20 wt-% of abietic acid to provide a resin solution; concentrating the obtained resin solution to provide a concentrated resin solution; providing a hydrogenated and/or partially hydrogenated vegetable oil, and a non-hydrogenated vegetable oil; mixing the hydrogenated and/or N partially hydrogenated vegetable oil with the non-hydrogenated vegetable oil to form an oil N base; mixing the concentrated resin solution with the oil base to provide a resin-oil mixture; S and wherein an antioxidant(s), preferably butylated hydroxyanisole (BHA) is added to the = resin solution, and/or to the resin-oil mixture, and that the amount of added antioxidant(s) = 30 is from 0.005 to 0.15 % (w/w), preferably from 0.01 to 0.1 wt-%, more preferably from 0.04 N to 0.06 wt-% of the total composition, wherein if the antioxidant is added to the resin-oil s mixture the concentrating of the resin solution is performed under vacuum.

N According to an embodiment of the disclosure the antioxidant is added to the resin solution. N Alternatively, or additionally the antioxidant(s) can be added to the resin-oil mixture, and thereafter cooling and homogenization of the composition.

Preferably the antioxidant is added into the resin solution before concentrating the resin solution.

Antioxidants are amongst the most popular skincare ingredients, but those have not typically been used in the traditional resin salves.

Common antioxidants in cosmetic compositions include compounds such as vitamins C and E, coenzyme Q10, Idebenone, zinc, copper and beta-carotene.

However, the list is endless, and there are millions of compounds with antioxidative properties, with many different functions.

Typically, antioxidants are added to the cosmetic products to increase the shelf life of the cosmetic composition by preventing degradation of natural ingredients (proteins, sugars, lipids) in the cosmetic product, and to prevent or alleviate the effects of aging, adverse effects of ultraviolet (UV) radiation i.e. sun damage including skin photoaging, photosensitivity reactions and immunological suppression, or other skin problems.

To achieve the best beneficial effects for the skin the antioxidants are usually being added during the last stages of the manufacturing processes of the cosmetic compositions.

However, since antioxidants were typically only added to the final products the ingredients in the compositions were prone to oxidation.

Surprisingly it was found that not all antioxidants are suitable for use in the method and composition of the invention.

Some of the antioxidants commonly used in cosmetics were readily degraded at higher temperatures and/or otherwise lost their antioxidant capacity for example during manufacturing and storage.

Moreover, the natural tocopherols in vegetable oils did not act as antioxidants i.e. to prevent oxidation of long chain fatty acids and resin acids.

Some common antioxidants also caused adverse effects to the structure of said composition.

In an embodiment the resin solution is concentrated under vacuum at pressure that is in the range of 30 — 500 mbar, preferably at 50 to 100 mbar and at temperature from ambient N (20 °C) to 60 °C, preferably from 35 °C to 45 °C, more preferably from 40 °C to 43 °C.

N Preferably, the resin solution is concentrated under vacuum when the antioxidant(s) is ? added to the resin-oil mixture.

In another embodiment, the antioxidant is added to the resin = solution and thereafter the resin solution is concentrated under vacuum at pressure that is = 30 in the range of 30 — 500 mbar, preferably at 50 to 100 mbar and at temperature from N ambient (20 °C) to 60 °C, preferably from 35 °C to 45 °C, more preferably from 40 °C to 43 3 °C.

O According to one preferable embodiment of the disclosure the resin solution is concentrated under vacuum at pressure of about 30 — 500 mbar, preferably at 50 to 100 mbar and at temperature from ambient (20 °C) to 60 °C, preferably from 35 °C to 45 °C, more preferably from 40 °C to 43 °C.

In an embodiment, the resin solution is concentrated to provide a concentrated resin acid solution by heating the solution at temperature from about 40 °C to 80 °C, preferably from 45 °C to 75 °C, more preferably from 65 °C to 70 °C, or until viscous yellowish-orange fluid is obtained. In an embodiment the resin acid solution is concentrated for a time that is approximately 2 hours, and the remaining ethanol in viscous fluid is < 5 weight-%, preferably approximately 1 weight-%.

According to the embodiments of the disclosure, the concentrating of the resin solution is performed by heating at temperature from about 40 °C to 80 °C, preferably from 45 °C to 75 °C, more preferably from 65 °C to 70 °C, or under vacuum, at pressure that is in the range of 30 — 500 mbar, preferably at 50 to 100 mbar and at temperature from ambient (20 °C) to 60 °C, preferably from 35 °C to 45 °C, more preferably from 40 °C to 43 °C. Typically, the resin solution 30 can be concentrated 110 by heating when the antioxidant(s) 90 is added to the resin solution 30 when dissolving 100 the resin acid fraction 10 with ethanol 20.

In an embodiment, the antioxidant or a mixture of antioxidants can also be added to the resin solution 30 when resin fraction 10 is dissolved into ethanol 20, and thereafter the resin solution 30 is concentrated under vacuum 110.

In the embodiments of the invention the resin/rosin of the composition is typically dissolved into ethanol in a ratio of resin to ethanol 3:7, preferably 3:6, more preferably 3:5, and most preferably 3:4. In one embodiment the coniferous resin acids are dissolved in ethanol in a ratio of 3:4 (resin:ethanol). The ratio of resin to ethanol can be larger as long as resin dissolves properly into ethanol. Also, the amount of ethanol can be larger if required to N 25 ensure the resin dissolves properly into ethanol. On the other hand, the amount of ethanol N should be as small as possible to minimize the time needed for ethanol evaporation. The S dissolvability of coniferous resin acids into ethanol can be improved by heating the resin ™~ solution. = a Typically, the resin/rosin is dissolved into ethanol at temperature of 50 to 70 °C, preferably N 30 at 65 °C until clear solution is obtained by continuously mixing and heating. According to 2 embodiments of the disclosure, the resin/rosin is dissolved into ethanol at temperature of O 50 to 70 °C, preferably at 65 °C until clear solution is obtained. In another embodiment, the method comprises dissolving the resin acid fraction 10 into ethanol 20, to provide a resin solution 30; concentrating the obtained resin solution 30 to provide a concentrated resin solution 40; mixing the hydrogenated 50 and/or partially hydrogenated vegetable oil 51 with the non-hydrogenated vegetable oil 60 to form an oil base 70; and mixing the concentrated resin solution 40 with the oil base 70 to provide a resin-oil mixture 80, wherein said dissolving 100, of the solution is performed under heating at temperature of 50 to 70 °C, preferably at 65 °C, said concentrating 110 is performed under heating at temperature from 40 °C to 80 °C, preferably from 45 °C to 75 °C, more preferably from 65 °C to 70 °C, or under vacuum, at pressure that is in the range of 30 — 500 mbar, preferably at 50 to 100 mbar and at temperature from ambient (20 °C) to 60 °C, preferably from 35 °C to 45 °C, more preferably from 40 °C to 43 °C. and mixing 120, 130 of the solutions is performed under heating at temperature of 60 °C to 80 °C, preferably 65 °C to 75 °C, and wherein an antioxidant(s) 90 is added to the resin solution 30, or to the resin-oil mixture 80, and that the amount of added antioxidant(s) 90 is in the range from

0.06 % (w/w). In an embodiment, the antioxidant(s) can be added both to the resin solution 30 and to the resin-oil mixture 80 regardless of how the concentrating of the resin solution is performed. Thus, the antioxidant(s) 90 can be added in several steps, and for example the more heat resistant antioxidant(s) 90 can be added to the resin solution 30 during the dissolving of the resin acid fraction 10 into ethanol 20, and for example more heat sensitive antioxidant(s) 90, such as alpha tocopherol, can be added to the resin-oil mixture 80. Typically, the dissolving 100, concentrating 110, and mixing 120, 130 can be performed under heating at temperatures from 50 °C to 80 °C, preferably at temperature from 60 to 80 °C, more preferably at temperature from 65 to 75 °C. However, lower temperatures can be used for example when the concentrating 110 is performed under vacuum, or when other means are utilized for accelerating the evaporation of ethanol, such as a stream of N nitrogen, and/or enhancing the mixing 120 of the hydrogenated 50 and/or partially N hydrogenated 51 vegetable oil with the non-hydrogenated vegetable oil 60, or enhancing S the mixing 130 of the concentrated resin solution 40 with the oil base 70. = According to embodiments of the disclosure, the method comprises

I & 30 providing a resin acid fraction 10; S dissolving the resin acid fraction 10 into ethanol 20, wherein the resin acid fraction 10 S comprises at least 70 wt-% of resin acids of which 4-10 wt-%, preferably 6 — 8 wt-% of N palustric acid to provide a resin solution 30; concentrating the obtained resin solution 30 to provide a concentrated resin solution 40;

providing a hydrogenated 50 and/or a partially hydrogenated vegetable oil 51, and a non- hydrogenated vegetable oil 60; mixing the hydrogenated 50 and/or the partially hydrogenated vegetable oil 51 with the non-hydrogenated vegetable oil 60 to form an oil base 70; mixing the concentrated resin solution 40 with the oil base 70 to provide a resin-oil mixture 80; and wherein an antioxidant(s) 90 is added to the resin solution 30, or to the resin-oil mixture 80 which resin-oil mixture 80 is obtained by concentrating the resin solution under vacuum and mixing the concentrated resin solution 40 with the oil base 70, and that the amount of added antioxidant(s) 90 is from 0.0051 to 0.15 % (w/w), preferably from 0.01 to 0.10 % (w/w), more preferably from 0.04 to 0.06 % (w/w) of the total composition.

According to the embodiments of the invention, the resin-oil mixture 80 is homogenized. The homogenization can be performed with any suitable equipment known to the person skilled in the art. Further, the homogenization can also be performed by vigorous mixing.

The amount of antioxidant(s) 90 should be as small as possible to avoid adverse effects to the structure of the salve composition, and to ensure that the antioxidant(s) do not perform as pro-oxidants. On the other hand, the amount of antioxidant(s) should be large enough to ensure the desired effects, i.e. avoiding or at least minimizing oxidation of the resin/rosin acids.

In another embodiment, the method comprises dissolving the resin acid fraction 10 into ethanol 20, to provide a resin solution 30; concentrating the obtained resin solution to provide a concentrated resin solution 40; mixing the hydrogenated 50 and/or partially hydrogenated 51 vegetable oil with the non-hydrogenated vegetable oil 60 to form an oil base 70; and mixing the concentrated resin solution 40 with the oil base 70 to provide a N 25 resin-oil mixture 80, and said dissolving, concentrating and mixing of the solutions is N performed under heating at temperature from 30 °C to 70 °C, preferably 40 °C to 60 °C 7 under a stream of nitrogen. Typically, in the oil base the amount of hydrogenated and/or partially hydrogenated E vegetable oil is from 0.1 to 30 wt-%, preferably from 1 to 20 % (w/w), more preferably from N 30 5 to 10 % (w/w) based on the total weight of the salve composition. The hydrogenated S and/or partially hydrogenated vegetable oil is used for controlling the viscosity of the salve S composition. In the embodiments of the invention, the oil base comprises hydrogenated and/or partially hydrogenated vegetable oil(s). Further, the oil base may optionally comprise fragrances, dyes, solidification point lowerers, biocides, or antibiotics. Moreover,

in the oil base the amount of vegetable oil, i.e. non-hydrogenated vegetable oil is in the range from 40 % to 92 % (w/w), preferably from 60 to 90 % (w/w), more preferably from 70 to 85 % (w/w) based on the total weight of the salve composition.

The vegetable oil may be used as such i.e. non-hydrogenated, or as partially hydrogenated or fully hydrogenated.

If vegetable oil is used as non-hydrogenated, for example 92% of the recipe, then the composition of the product changes from an ointment to a flowing liniment.

Further, said vegetable oils may be non-hydrogenated, partially hydrogenated or hydrogenated.

In an embodiment for example soybean oil may be non-hydrogenated or partially hydrogenated, and other oils such as cottonseed oil may be hydrogenated, and palm oil may be hydrogenated.

According to the embodiments of the disclosure, the salve composition is a salve composition comprising coniferous resin acids, oil base and an added antioxidant or a mixture of antioxidants, wherein the coniferous resin acids are provided as resin acid fraction that comprises at least 70 wt-% of resin acids of which 4-10 wt-%, preferably 6 — 8 wt-% of palustric acid, the oil base comprises hydrogenated vegetable oil and/or partially hydrogenated vegetable oil as a mixture with non-hydrogenated vegetable oil, and the amount of added antioxidant(s) is from 0.005 to 0.15 % (w/w), preferably from 0.01 to 0.1 % (w/w), more preferably from 0.04 to 0.06 % (w/w) of the total composition.

Said salve composition may optionally contain other ingredients such as fragrances, dyes, solidification point lowerers, biocides, or antibiotics.

Other active agents may be added depending on the desired purpose of use of the salve composition to enhance and/or obtain additional benefits for the salve/ointment composition.

Still typically, the salve composition comprises an antioxidant or a mixture of antioxidants in an amount of 0.005 % to 0.15 % (w/w), preferably from 0.01 % to 0.10 % (w/w), more A 25 preferably from 0.04 % to 0.06 % (w/w) of the total composition.

S The antioxidant suitable for use in the composition of the invention can be selected from N antioxidants officially approved for use in cosmetic products (Regulation (EC) N° ~ 1223/2009). The antioxidants suitable for use in the invention include but are not limited to T butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), a-tocopheryl acetate N 30 (ATA), propyl gallate, dodecyl gallate, tert-butyl hydroquinone (TBHQ), 2,4,5- s trihydroxybutyrophenone (THBP), hydroxy methyl di-tertiary butyl phenol, and ascorbyl N palmitate (AP). If alpha tocopherol (AT) or ascorbyl palmitate is added to the composition, N they should be added in combination with other antioxidants.

Preferably the added antioxidant is selected from group consisting of butylated hydroxy anisole (BHA) and butylated hydroxy toluene (BHT). More preferably, the antioxidant is butylated hydroxy anisole (BHA) alone or in combination with other antioxidants, such as butylated hydroxy toluene (BHT), o-tocopheryl acetate (ATA) or ascorbyl palmitate (AP). Still more preferably, the antioxidant is selected from the group consisting of but not limited to dodecyl gallate, propyl gallate, tert-butyl hydroquinone (TBHQ), 2,4,5- trihydroxybutyrophenone (THBP), hydroxy methyl ditertiary butylphenol, butylated hydroxy anisole (BHA), and butylated hydroxytoluene (BHT), and the antioxidant is used alone or in combination with antioxidants selected from group consisting of but not limited to a- tocopherol, a-tocopheryl acetate (ATA), ascorbyl palmitate (AP), dodecyl gallate, propyl gallate, tert-butyl hydroquinone (TBHQ), 2,4,5-trihydroxybutyrophenone (THBP), hydroxy methyl ditertiary butylphenol, butylated hydroxy anisole (BHA), and butylated hydroxytoluene (BHT), preferably the antioxidant is butylated hydroxy anisole (BHA) alone or in combination with other antioxidants. The resin/rosin of the composition is obtained from resin acid fraction obtained by distilling crude tall oil derived from kraft pulping process of wood. Alternatively, the resin/rosin can be obtained from resin acid fraction obtained by distilling gum and/or wood rosin. The coniferous resin acids can be provided as a solution or in powdery or granulated form. Preferably the coniferous resin acid fraction is solid at room temperature. The resin acids are provided as a resin acid fraction comprising at least 70 to 99 weight-%, preferably at least 80-90 weight-% of resin acids based on total weight of the resin composition. Thus, according to embodiments of the disclosure the resin acid fraction comprises at least 70 weight-% of resin acids based on total weight of the resin composition. The resin/rosin of the composition comprises at least 4 to 10 weight-% of palustric acid. In an embodiment, the amount of palustric acid is at least 4 to 10 w-% of the rosin/resin acid composition, preferably from 6 to 10 w-%, more preferably from 6 to 8 w-%. N Typically, the salve composition comprises resin acids in an amount of 0.1 to 30 wt-%, N preferably 1 to 20 wt-%, more preferably 5 to 10 wt-% of the final salve composition. The 7 amount of the resin acids may be larger as long as it does not adversely affect the structure of the composition.

I E 30 The resin/rosin acid fraction comprises about 4 to 10 weight-%, preferably from 6 to 8 N weight-% of palustric acid, = 20 weight-% of abietic acid, and = 70 weight-% of abietic type S rosin acids. The abietic type rosin acids mean here tricyclic diterpene monocarbonic acids S with isopropyl side chain.

In Figure 1 a resin acid fraction 10 is dissolved 100 into ethanol 20 to provide a resin solution 30. An antioxidant(s) 90 is added to the resin solution 30. The obtained resin solution 30 is concentrated 110 to obtain concentrated resin solution 40. Hydrogenated vegetable oil 50 and/or partially hydrogenated vegetable oil 51 are mixed 120 with a non- hydrogenated vegetable oil 60 to form an oil base 70. Said concentrated resin solution 40 is then mixed 130 with the oil base 70 to provide a resin-oil mixture 80. In the embodiments of the disclosure, the resin-oil mixture 80 is homogenized 140 to obtain a salve composition comprising coniferous resin acids 82. In Figure 2 a resin acid fraction 10 is dissolved 100 into ethanol 20 to provide a resin solution 30. The obtained resin solution 30 is concentrated 110 under vacuum to obtain concentrated resin solution 40. Hydrogenated vegetable oil 50 and/or partially hydrogenated vegetable oil 51 are mixed 120 with a non-hydrogenated vegetable oil 60 to form an oil base 70. Said concentrated resin solution 40 is then mixed 130 with the oil base 70 to provide a resin-oil mixture 80. Thereafter an antioxidant or a mixture of antioxidants 90 is added to the resin-oil mixture 80. Optionally, the antioxidant or a mixture of antioxidants 90 can also be added to the resin solution 30 when resin fraction 10 is dissolved 100 into ethanol 20. The salve composition of the invention is obtainable by the method of the invention.

The disclosure is also directed to use of the salve/ointment composition in a method for the treatment of skin disorders in humans and animals.

Said salve composition comprising coniferous resin acids is suitable for use in a method for treating psoriasis, atopic dermatitis, skin burns, and wounds.

Still further, the salve composition is suitable for use in a method for treating pressure sores, eczemas, rashes, gashes, cuts, slashes, stabs, punctures, burns, scalds, lacerations, lacerated wounds, penetrating wounds, bullet wounds, contusions, ulcers, incised wounds, or stretch marks.

Thus, the salve composition N can be used in a method for treating psoriasis, atopic dermatitis, skin burns, wounds, N infected and non-infected, acute and chronic wounds, scalloping, skin breakdowns, 7 pressure sores and burns, dandruff, flaking, seborrhoea, rosacea, pressure sores, eczemas, rashes, gashes, cuts, slashes, stabs, punctures, burns, scalds, lacerations, = 30 lacerated wounds, penetrating wounds, bullet wounds, contusions, ulcers, incised wounds, N stretch marks, viral infections, such as herpes simplex, bacterial, and/or fungal infections, 3 dermatophytes, dermatomycosis, onychomycosis, dry skin and/or moisture poor skin in O humans and animals.

The composition according to the invention is stable and does not form crystallized structure upon storage.

The structure of the composition is smooth, and it remains stable upon storage with no separation of liquids or formation of crystals.

The composition can be stored at elevated temperatures without adverse effects on the structure and/or visual or sensory quality of the composition.

Moreover, with the composition according to the invention it is possible to avoid or at least minimize allergic reactions typically caused by oxidation products i.e. hydroxylated forms of resin acids.

Typically, in the salve composition comprising coniferous resin acids the recovery % of abietic acid vs theoretical is at least 70 %, preferably at least 75 %, more preferably = 84 %. The abietic acid recovery for 100 % sample preparation was 87.4 % (deviation 0.5 %) as determined by ASTM D5974 method.

The recovery % was calculated by dividing the measured abietic acid amount with the calculated theoretical abietic acid amount and multiplying with 100. Thus, the recovery % of abietic acid vs theoretical is at least 70 %, and the recovery % is a value selected from any one of the following: 70, 71, 72, 73, 74, 75,76,77,78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, and 100 %. Preferably the abietic acid recovery is at least 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 %, more preferably at least 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100 %. The abietic acid recovery can vary depending on the analytical method used for measuring the sample abietic acid content.

In embodiments of the invention, the salve composition comprises vegetable oils as such, i.e. non-hydrogenated vegetable oils, or as partially hydrogenated or hydrogenated vegetable oils.

In an embodiment the vegetable oil is selected from a group consisting of rapeseed, sunflower, coconut, linseed, canola, palm, olive, soybean, cotton, corn, acai palm, palm kernel, brazil nut, peanut, castor bean, avocado, safflower, pumpkin seed, colza, peanut, walnut, hempseed, or nut oil or any mixtures thereof.

The product according to the invention is well tolerated, because when administered to a N subject, it does not cause any adverse effects or at least allergic reactions are minimized.

N The salve/ointment product according to the invention is suitable for use in a method for 7 the treatment of skin burns, wounds and psoriasis.

The composition can also be used in a method for the treatment of skin disorders, such as inflammatory skin disorders like atopic E 30 dermatitis or skin rashes formed through inflammatory mechanisms or via microbial N attacks.

The composition is suitable for use in a method for treating psoriasis, atopic 3 dermatitis, skin burns, wounds, infected and non-infected, acute and chronic wounds, N scalloping, skin breakdowns, pressure sores and burns, dandruff, flaking, seborrhoea, rosacea, pressure sores, eczemas, rashes, gashes, cuts, slashes, stabs, punctures, burns, scalds, lacerations, lacerated wounds, penetrating wounds, bullet wounds,

contusions, ulcers, incised wounds, stretch marks, viral infections, such as herpes simplex, bacterial and/or fungal infections, dry skin and/or moisture poor skin in humans and animals.

Moreover, the salve composition is a topical composition for use in a method for treating skin wounds, ulcers, scallops and abrasions.

It is also suitable for use in a method for the treatment of chronic wounds that are difficult to treat.

It promotes wound healing and has antimicrobial, bacterial, viral and fungal growth inhibitory action.

Said composition is also suitable for use in a method for treating scaling of the skin and scalp and psoriasis.

The salve composition softens, protects and moisturizes animal paws, footpads and hooves.

Further, the salve composition is anhydrous and will not freeze.

Said composition tolerates momentary freezing, and it can also be stored and used in cold climates if needed.

The cold tolerance of the salve composition depends on the amount of the polyunsaturated fatty acids in the oil base.

The ointment/salve composition has both antibacterial and antifungal activity against the most typical Gram-positive and Gram-negative bacteria that cause wound infections, and dermophytes, or filamentous fungi, which cause fungal infections of the skin and nails.

The salve composition is also suitable for use in methods for treating viral infections, such as herpes simplex virus.

Said composition is well suited for the local treatment of infected and non-infected, acute and chronic wounds, scallops, skin breakdowns, pressure sores and burns in open and hospital care.

For animals, the salve composition can be applied to the skin, paws, footpads or hooves, including under the shoe and into the nail holes.

The salve composition quickly reduces the amount of inflammatory secretions, and it can also be applied on ear lobes.

The obtained salve composition comprising coniferous resin acids is made with natural ingredients, and the salve composition is breathable and smooth.

It does not clog pores, N and/or promote acne or other inflammatory reactions on the skin.

It is well tolerated and N provides a good protective film on the skin surface.

Preferably the salve composition does S not comprise any unbreathable ingredients, such as petrolatum.

However, if petrolatum is = used for example for increasing the viscosity of the salve product, its content is preferably E 30 minimized.

N The following examples 1 to 4 are comparative examples and present the results obtained 3 from preliminary experiments made when optimizing the method for manufacturing of the N salve composition comprising coniferous resin acids.

Further, in examples 5 and 6 it is N presented the method for manufacturing of the salve composition according to the invention.

Use of the salve composition in a method for treating skin disorders is presented in examples 7 to 12, and these results were obtained from preliminary tests made with the salve composition manufactured according to method described in examples 5 and 6.

EXAMPLES Example 1 - Comparative The antioxidant suitable for use in the invention was selected based on preliminary experiments performed with various antioxidants. Table 1 presents peroxide values (milliequivalent of active oxygen, i.e. the quantity of peroxide, contained in 1000 g of substance) of salve formulations comprising different antioxidants. The samples were measured by forced degradation stress test, and the antioxidants were added to the final product. As can be seen from table 1 higher amount of peroxides were obtained in samples without antioxidant(s). Table 1 Peroxide value (milliequivalent of active oxygen (the quantity of peroxide) contained in 1000g of substance) Sample 3d70°C Code open container E2001 + TA N E2001 + TA s

N

S o aceno

PP I The identifiers of the samples in tables 1, 2, 3 and 4 are as follows: sample x70-19 is an - ointment/salve composition E2001 with added tocopherylacetate (TA), sample x71-19 is

PP S an ointment/salve composition E2001 with added antioxidant butylated hydroxyanisole

LO < 20 (BHA), sample x72-19 is an ointment/salve composition E2001 with added antioxidant N butylated hydroxytoluene (BHT), sample x73-19 is an ointment/salve composition E2001 with added antioxidants ascorpyl palmitate and butylated hydroxytoluene, sample x74-19 is an ointment/salve composition E2001 with added antioxidants tocopherylacetate and butylated hydroxyanisole, sample x75-19 is an ointment/salve composition E2001 with added antioxidants tocopherylacetate and butylated hydroxytoluene, sample x63-19 is an ointment/salve composition E2001 Placebo without added resin acids and antioxidants.

It was seen from sample x70-19 containing tocopheryl acetate that added tocopheryl acetate did not prevent the oxidation of the salve ingredients. High peroxide value was also seen with Sample x63-19 that did not contain any antioxidants and resin/rosin acids. Further, it can be seen that at initial the peroxide values were significantly lower in samples with added antioxidants. Thus, it can be concluded that the added antioxidants lower the amounts of active oxygen, whereas the double bonds of unsaturated fatty acids in vegetable oil increase the amount of active oxygen. As expected, it was noticed that the active oxygen increased when stored open. The active oxygen was very high in sample x70-19, and said sample also turned into non- homogeneous indicating that the added antioxidant (alpha tocopheryl acetate) had been degraded by be influence of heat. Further, the amount of active oxygen was very high in sample x63-19 without added antioxidants and resin/rosin acids. According to the forced degradation stress test the best antioxidants seemed to be BHA and BHT (samples x71- 19 and x72-19). The appearance of the tested samples was evaluated, and the results are presented in the following table 2. It was seen that samples x73-19 (E2001 + APBHT), x74-19 (E2001 + TA + BHA), x75-19 (E2001 + TA + BHT) and x63-19 (E2001 Placebo without added antioxidants and resin/rosin acids) were yellowish solid ointments with some mobility at 50 °C, and the samples were solidified properly at room temperature. Thus, it can be concluded that the structure of the samples containing antioxidant mixtures, such as ascorbyl palmitate + BHT, tocopheryl acetate + BHA, or tocopheryl acetate + BHT, was N more unstable than the structure of other samples when stored for 3 days at 50 *C. The N same instability was observed with the structure of the placebo composition (no added 7 antioxidants or resin/rosin acids). Further, all samples containing resin/rosin acids were - yellowish solid ointments with white spots on surface after storage for 7 weeks at 50 °C in E 30 a closed container. N It was also seen that white spots were increased on the surface of sample x70-19 (added S tocopheryl acetate) when stored for 1 to 7 days at 50 °C. This observation was in line with S the results obtained in forced degradation stress test and confirmed the observation that alpha tocopheryl acetate does not maintain its antioxidant activity at high temperatures.

Moreover, it can also be seen from table 2 that all samples turned liquid at 70 °C. Therefore, it can be concluded that the salve composition should preferably be stored at temperatures < 50 °C. Table 2 Appearance of the tested (in the forced degradation stress test) samples 6h50|/1 d 503d507 d 50/3 d 5013 dl, week 'C 'C 'C 'C 'C 70 °C . Sample , , , , 50 Cc Code closed closed closed c osed open |open | od contai | contain |contai | contain |contai | cont : ; container ner er ner er ner ainer 6919 [F000 je ja ja Ja | je jaf | E2001 + | E2001 + | E2001 + : E2001 + x | E2001 + x | E2001 + x | E2001 x e) yellowish solid ointment, (* some mobility when turned at 50 °C; solidifies properly at RT) f) yellowish solid ointment with small white spots on surface, number of spots (increase of spots during stability observed with x70-19)

N

QA S g) liquid at 70 °C, yellowish mobile ointment at RT; heating therefore breaks the structure of S ointment

NN - h) pale solid ointment with white spots on surface

I E i) yellowish solid ointment with white spots on surface (X70-10, X71-19, X72-19, X75-19 have N more spots than X73-19 and X74-19)

LO S The forced degradation stress test showed that the best results were obtained with BHA

O N as an added antioxidant, because said composition tolerated elevated temperatures.

Furthermore, the most homogeneous structure was also obtained with BHA as an antioxidant. In previous tests, there were indications that the post-production concentration of abietic acid differs from the theoretical added amount; yields were 70-80% of theory. The yield of sample treatment was confirmed to be 87% (resin + placebo, vs determined resin) and the recovery of abietic acid as such was 99%. Thus, no decrease indicative of abietic acid degradation in sample processing was observed, but a slight decrease for other unspecified reason. Taking into account the yield factor of the method, which was 0.87, the deviation of the prepared from the theoretical is slightly smaller (i.e. 70-80, respectively 80-92), but still significant. Open container 3d 70 °C degradation test + air exposure showed significant (~ 70%) degradation without antioxidant but about -30% with antioxidant (BHA, BHT). Given this observation, the plan was to examine the effect of process parameters and manufacturing method on the abietic acid content of E2001 ointment.

Example 2 (without antioxidant) - Comparative Coniferous resin salve was prepared by dissolving 50 g of coniferous resin (commercial resin fraction comprising about 80 wt-% resin acids, and 6 — 8 % palustric acid as determined by ASTM D5974 method) into 66.6 g of ethanol (ratio 3:4, resin:EtOH) by mixing in a beaker at 65 °C — 75 °C until clear solution was obtained (about 15 to 30 minutes). Then, the obtained resin solution was concentrated at 65 °C — 75 °C until viscous yellowish-orange fluid was obtained (approximately 2 hours). After concentrating the remaining ethanol content of the resin solution was approximately 1 %. Next, 40.0 g of hydrogenated vegetable oil Dermofeel Viscolid from Evonik Dr Straetmans e 29 was mixed with 410 g of non-hydrogenated vegetable oil, Grapeseed oil, Textron Evoil O Grapeseed REF001 by mixing in a beaker at 70 *C — 80 *C until clear solution (oil base) N was obtained (about 5 minutes). Thereafter, the oil base was mixed with the concentrated K resin solution with continuous mixing at 65 °C — 75 °C until clear solution was obtained (for about 30 — 60 minutes). Then, the composition was allowed to cool with slowly mixing until & 30 the temperature was 35 °C — 40 °C and opacity started to appear to the solution. Finally, N the composition was homogenized for < 1 minutes at about 17500 rpm, and viscous S ointment with gel structure was obtained. The total manufacturing time was about 3 hours. S The salve composition was allowed to cool and transferred to a storage container for storage at 15 °C — 25 °C.

The thus obtained salve composition was measured by forced degradation stress test, wherein abietic acid content was measured from salve samples stored at different temperatures in open and closed containers.

The resin/rosin acids were extracted from the salve sample with acetone.

Accurately about 0.34 g of salve was weighed to suitable closable container (50 ml centrifuge tube). Then 8 ml of acetone was added, and more solvent (acetone) was added to remove the sample attached to walls of container until all sample was in container.

Thereafter, the sample was sonicated for 120 min at room temperature and cooled.

After sonication, the sample was mixed with Vortex for about 60 seconds and then cooled in an ice bath in order to solidify the sample.

Thereafter, said sample was filtered to a round-bottomed flask through a filter paper (Whatman/Black ribbon pre-rinsed with acetone). After filtration the filter paper was flushed with small volume of acetone and flushing solution was added to the sample solution.

Finally, the sample solution was evaporated to absolute dryness overnight in the hood.

The abietic acid content of the extracted salve sample was measured by ASTM D5974 method.

The measured initial abietic acid content of the salve composition was 40.3 mg/g.

The theoretical abietic acid content was calculated based on the added amount of resin (50 9/500 9) after ethanol evaporation.

The abietic acid content of the resin batch was 548.153 mg/g based on two 34 mg determination in the accuracy study, and therefore the theoretical abietic acid content was 54.8 mg/g.

Thus, the calculated abietic acid result vs. theoretical was 73.5 %. The forced degradation stress test showed that the salve composition stored for 7 days at 50 °C in a closed container remained stable as well as the same salve composition stored for 7 week at 50 °C in a closed container, but the salve samples stored in open containers for 3 days at 50 °C and at 70 °C showed significant reduction in the abietic acid contents (abietic acid contents were 37.9 mg/g and 11.1 mg/g respectively). Consequently, without N antioxidant(s) 72.4 % of the added abietic acid was degraded at 70 °C.

Thus, it can be O concluded that the reduction of the abietic acid content is due to oxidation, and it is evident N that exposure to air and light clearly accelerates the oxidation reactions as expected. ™~ E 30 Example 3 (antioxidant(s) in the end) - Comparative N 6 batches of coniferous resin salve were prepared by dissolving 6x 50 g of coniferous resin 3 (commercial resin fraction comprising about 80 wt-% resin acids, and 6 — 8 wt-% of N palustric acid as determined by ASTM D5974 method) into 6 x 66.6 g of ethanol (ratio 3:4, N resin:EtOH) by mixing in a beaker at 65 °C — 75 °C until clear solutions were obtained (about 15 to 30 minutes). Then, the obtained 6 resin solutions were concentrated by heating at 65 °C — 75 °C until viscous yellowish-orange fluids were obtained (approximately 2 hours). After concentrating the remaining ethanol content of the resin solution was approximately 1 %.

Next, 6 x 40.0 g of hydrogenated vegetable oil Dermofeel Viscolid from Evonik Dr Straetmans was mixed with 6 x 410 g of non-hydrogenated vegetable oil, Grapeseed oil, Textron Evoil Grapeseed REF001 by mixing in a beaker at 70 °C — 80 °C until clear solution (oil base) was obtained (about 5 minutes). Thereafter, the oil bases were mixed with the concentrated resin solution with continuous mixing at 65 °C — 75 °C until clear solutions were obtained (for about 30 — 60 minutes). Next, 0.05 % (w/w) of antioxidant(s), such as alpha tocopheryl acetate, butylated hydroxyanisole (BHA), butylated hydroxy toluene (BHT), or antioxidant mixtures, such as ascorbyl palmitate + butylated hydroxy toluene, tocopheryl acetate + butylated hydroxy anisole, and tocopheryl acetate + butylated hydroxy toluene were added to the compositions at temperature of 45 — 50 °C. Then, the composition was allowed to cool with slowly mixing until the temperature was 35 °C — 40 °C and opacity started to appear to the solutions. Finally, the compositions were homogenized for < 1 minutes at about 17500 rpm, and viscous ointments with gel structure were obtained. The total manufacturing time was about 3 hours and 20 minutes. The salve compositions were allowed to cool and transferred to storage containers for storage at 15 °C — 25 €.

The thus obtained salve compositions were measured by forced degradation stress test, wherein abietic acid content was measured from salve samples stored at different temperatures in open and closed containers. The resin/rosin acids were extracted from the salve samples as described in example 2, and the abietic acid content was measured by ASTM D5974 method. The measured initial abietic acid contents and the calculated abietic acid result vs. theoretical are presented in table 3. The measured initial abietic acid content N of the salve compositions were: X70-19 41.2 mg/g (sample containing tocopheryl acetate), N X71-19 42.4 mg/g (sample containing BHA), X72-19 42.6 mg/g (sample containing S butylated hydroxytoluene), X73-19 39.2 (sample containing ascorbyl palmitate+butylated = hydroxytoluene), X74-19 42.4 mg/g (sample containing tocopheryl acetate+butylated = 30 hydroxy anisole), X75-19 39.7 mg/g (sample containing tocopheryl acetate+butylated N hydroxytoluene). The theoretical abietic acid content was calculated based on the added s amount of resin (50 g/500 g) after ethanol evaporation. The abietic acid content of the resin N batch was 548.153 mg/g based on two 34 mg determination in the accuracy study, and N therefore the theoretical abietic acid content was 54.8 mg/g. Thus, the calculated abietic acid result vs. theoretical was batch X70-19 75.2 %, X71-19 77.4, X72-19 77.7 %, X73-19

71.5 %, X74-19 77.4 %, X75-19 72.5 %. Table 3 The measured initial abietic acid contents and the calculated abietic acid result vs. theoretical (antioxidant was added in the end of the manufacturing process) Sample Initial abietic acid contents | Abietic acid result vs mg/g theoretical % The forced degradation stress test showed that the salve compositions stored for 7 days at 50 °C in closed containers remained rather stable as well as the same salve compositions stored for 7 week at 50 °C in a closed container, but the salve samples stored in open containers for 3 days at 50 °C and at 70 °C showed significant reduction in the abietic acid contents. The abietic acid contents of the samples stored in open containers for 3 days at 50 °C and at 70 °C are presented in table 4. The abietic acid contents were X70-19 40.7 mg/g, X71-1939.6 mg/g, X72-19 37.2 mg/g, X73-19 34.2 mg/g, X74-19 40.4 mg/g, and X75-19 43.1 mg/g, and X70-19 0 (degradation), X71-1927.9 mg/g, X72-19

31.0 mg/g, X73-19 20.1 mg/g, X74-19 26.1 mg/g, X75-19 30.5 mg/g respectively. Surprisingly, batch X70-19 containing tocopheryl acetate did not contain any abietic acid N after storage at 70 *C for 3 days in an open container. It seems that the abietic acid was

O N completely oxidised, and the antioxidant tocopherylacetate did not withstand high S temperatures and it was degraded. Thus, it can be concluded that the reduction of the = abietic acid content is due to oxidation, and it is clear that exposure to air and light clearly E 20 accelerates the oxidation reactions as expected.

NN

N <t

LO O QA O N

Table 4 The abietic acid contents of the samples stored in open containers for 3 days at 50°C and at 70 °C Sample Sample stored at 50 °C | Sample stored at 70 °C Abietic acid content mg/g Abietic acid content mg/g The calculated abietic acid result vs. theoretical was higher for batches containing butylated hydroxyanisole or butylated hydroxytoluene. However, some phase separation was observed for batches containing solely butylated hydroxytoluene or tocopheryl acetate, or a combination of ascorbyl palmitate and butylated hydroxytoluene. Thus, based on this comparative example butylated hydroxyanisole seems to be the most potent antioxidant for use in the salve product.

Example 4 (BHA in the end and temperature control) - Comparative Coniferous resin salve was prepared by dissolving 50 g of coniferous resin (commercial resin fraction comprising about 80 w-% resin acids, and 6 — 8 % palustric acid as N determined by ASTM D5974 method) into 66.6 g of ethanol (ratio 3:4, resin:EtOH) by

N S 15 mixing in a beaker at 65 °C until clear solution was obtained (10 minutes). Then, the N obtained resin solution was concentrated at 65 °C until viscous yellowish-orange fluid was N obtained (2 hours 15 minutes). After concentrating the remaining ethanol content of the r resin solution was approximately 1 — 5 %. a a N Next, 40.0 g of hydrogenated vegetable oil Dermofeel Viscolid from Evonik Dr Straetmans 3 20 was mixed with 410 g of non-hydrogenated vegetable oil, Grapeseed oil, Textron Evoil N Grapeseed REF001 by mixing in a beaker at 65 °C —70 °C until clear solution (oil base)

N was obtained (15 minutes). Thereafter, the oil base was mixed with the concentrated resin solution with continuous mixing at 65 *C until clear solution was obtained (10 minutes).

Next, 0.25 g of butylated hydroxyanisole (BHA) was added to the solution at 65 °C for 10 minutes until clear solution was obtained.

Then heating was stopped.

Thereafter, the composition was allowed to cool with slowly mixing for 30 minutes until the temperature was 35 °C — 40 °C and opacity started to appear to the solution.

Finally, the composition was homogenized for < 1 minutes at about 17500 rpm avoiding contact with air.

The salve composition was allowed to cool to room temperature.

The obtained salve composition was a yellowish creamy ointment.

The resin/rosin acids were extracted from the salve sample as described in example 2, and the abietic acid content was measured by ASTM D5974 method.

The measured initial abietic acid content of the salve composition was 43.1 mg/g.

The theoretical abietic acid content was calculated based on the added amount of resin (50 g/500 g) after ethanol evaporation.

Resin batch abietic acid content 548.153 mg/g, based on two 34 mg determination in the accuracy study, corresponds to the theoretical resin content 54.8 mg/g in the ointment.

Thus, the calculated abietic acid result vs. theoretical was 79 %. The determined recovery for 100 % sample preparation was 87 %. Example 5 antioxidant (BHA) in the beginning Coniferous resin salve was prepared by dissolving 50 g of coniferous resin (commercial resin fraction comprising about 80 w-% resin acids, and 6 — 8 % palustric acid as determined by ASTM D5974 method) into 66.6 g of ethanol (ratio 3:4, resin:EtOH) by mixing in a beaker at 65 °C until clear solution was obtained (10 minutes). Next, 0.25 g of butylated hydroxyanisole was added to the resin solution and mixed for 5 minutes or until clear solution was obtained at 65 °C.

Then, the obtained resin solution was concentrated A at 65 °C until viscous yellowish-orange fluid was obtained (1 hour 45 minutes). After O 25 concentrating the remaining ethanol content of the resin solution was approximately 1 — 5 S %. == Next, 40.0 g of hydrogenated vegetable oil Dermofeel Viscolid from Evonik Dr Straetmans E was mixed with 410 g of non-hydrogenated vegetable oil, Grapeseed oil, Textron Evoil N Grapeseed REF001 by mixing in a beaker at 65 °C —70 °C until clear solution (oil base) m 30 was obtained (15 minutes). Thereafter, the oil base was mixed with the concentrated resin N solution with continuous mixing at 65 °C until clear solution was obtained (15 minutes), N and heating was stopped.

Thereafter, the composition was allowed to cool with slowly mixing for 30 minutes until the temperature was 35 °C — 40 °C and opacity started to appear to the solution. Finally, the composition was homogenized for < 1 minutes at about 17500 rpm avoiding contact with air. The salve composition was allowed to cool to room temperature. The obtained salve composition was a yellowish translucent ointment. The resin/rosin acids were extracted from the salve sample as described in example 2, and the abietic acid content was measured by ASTM D5974 method. The measured initial abietic acid content of the salve composition was 47.2 mg/g. The theoretical abietic acid content was calculated based on the added amount of resin (50 g/500 g) after ethanol evaporation. Resin batch abietic acid content 548.153 mg/g, based on two 34 mg determination in the accuracy study, corresponds to the theoretical resin content 54.8 mg/g in the ointment. Thus, the calculated abietic acid result vs. theoretical was 86%. The determined recovery for 100 % sample preparation was 87 %. Thus, recovery factor (RF) was 0.87. The example 5 clearly showed that by adding the antioxidant in the beginning of the manufacturing process it is possible to improve abietic acid yields and thus also minimize the loss of abietic acid due to oxidation. Example 6 adding antioxidant in the end and concentrating the resin solution under vacuum Coniferous resin salve was prepared by dissolving 50 g of coniferous resin (commercial resin fraction comprising about 80 w-% resin acids, and 6 — 8 % palustric acid as determined by ASTM D5974 method) into 66.6 g of ethanol (ratio 3:4, resin:EtOH) by mixing at 65 °C until clear solution was obtained (15 minutes). Then, the obtained resin solution was concentrated under vacuum (about 50 to 100 mbar) at about 40 °C until viscous yellowish-orange fluid was obtained (50 minutes). After concentrating the N remaining ethanol content of the resin solution was approximately 1 — 5 %.

S N 25 Next, 40.0 g of hydrogenated vegetable oil Dermofeel Viscolid from Evonik Dr Straetmans S was mixed with 410 g of non-hydrogenated vegetable oil, Grapeseed oil, Textron Evoil == Grapeseed REF001 by mixing in a beaker at 65 °C — 70 °C until clear solution (oil base) E was obtained (15 minutes). Thereafter, the oil base was mixed with the concentrated resin N solution with continuous mixing at 65 *C until clear solution was obtained (15 minutes). m 30 Next, 0.25 g of butylated hydroxyanisole was added to the composition and mixed for 10 N minutes or until clear solution was obtained at 65 °C, and heating was stopped. Thereafter, N the composition was allowed to cool with slowly mixing for 30 minutes until the temperature was 35 °C — 40 °C and opacity started to appear to the solution. Finally, the composition was homogenized for < 1 minutes at about 17500 rpm avoiding contact with air.

The salve composition was allowed to cool to room temperature.

The obtained salve composition was a yellowish translucent ointment.

The measured initial abietic acid content of the salve composition was 45.4 mg/g.

Resin batch abietic acid content 622.0 mg/g, based on two 34 mg determination in the accuracy study, corresponds to the theoretical resin content 62.2 mg/g in the ointment.

The determined recovery for 100 % sample preparation was 87 %, d= 0.5 % (87.36 %). Thus, the calculated abietic acid result vs. theoretical RF 0.87 was 84 %. This example showed that by concentrating the resin solution under vacuum it is possible to improve abietic acid yields and thus also minimize the loss of abietic acid due to oxidation even though the antioxidant is added in the end of the manufacturing process.

Thus, it can be concluded that even better abietic acid yields could possibly be obtained if the antioxidant is added in the beginning of the manufacturing process to the resin solution and said resin solution is thereafter concentrated under vacuum avoiding using high temperatures.

Conclusions Heating was required for dissolving the resin in EtOH and concentrating the solution and combining the resin concentrate with the oil phase.

Also, it was noticed that attention had to be paid to more controlled temperature use as disclosed in comparative example 4. In the process, the evaporation of ethanol was performed by heating, whereby the A evaporation temperature of 65 °C — 75 °C, a time of about 2 h, caused a significant O 25 temperature stress.

It was noticed that this could be reduced by vacuum evaporation at a N lower temperature (example 6). == Moreover, it was found out that the antioxidant could protect the resin compounds if added E already during the dissolution step (example 5). N When different antioxidants and process parameters were tested, it was seen that the S 30 addition of antioxidant at the same time as dissolving the resin acid fraction into ethanol N clearly prevented abietic acid loss due to oxidation.

The influence of manufacture process parameters on the abietic acid content of the salve is presented in table 5. The results showed that the best abietic acid yield was obtained when the antioxidant was added in the beginning of the manufacturing process. Good results were also obtained when the resin solution was concentrated under vacuum at low temperature. Table 5 The influence of manufacture process parameters on the abietic acid content of the salve Abietic acid vs theoretical | Improvement Example | Lot | (%) (+) Description BHA in the end and 4 79 55 temperature control Concentrated with 11 | 84 10.5 rotavapor, lower T Abietic acid measurement recovery was 99% N Abietic acid recovery for 100 % sample preparation was 87,4 % (deviation 0,5 %) & S Deviation between measurements was 1,1-1,6%.

NN = The effect of different antioxidants on abietic acid yields and homogeneity of the salve a N composition were compared. It was noticed that some antioxidants caused adverse effects s on the structure of the composition. For example, tocopherol acetate did not withstand high N temperatures and oxidation of the salve ingredients. The BHT formula caused adverse N 10 effects on the structure of the salve composition as some phase separation was observed after sample treatment. Further, it was noticed that the BHA formula could withstand high temperatures, such as at least 50 °C. After preliminary tests, the right process parameters were obtained that enabled the manufacturing of salve product with good quality, and long shelf life.

Example 7 treating a surgical wound The resin salve composition was manufactured according to the invention. The salve composition was used in a method for treating surgical wound. Wound salve/ointment was used in a method for treating skating injury in a teenage girl. The ointment was applied to the wound and the wound was bandaged with a wound dressing. The wound was initially treated by cleaning it with water and drying once a day. The wound salve was applied directly to the area to be treated and the wound was covered with a breathable wound dressing. After a week, the treatment was continued every two days. Following the treatment, the wound healed rapidly and did not become infected. A significant wound healing was observed between days 2 and 18. Example 8 treating nail fungus and cuticle inflammation The resin salve/ointment composition was manufactured according to the invention. The ointment was used in a method for treating nail fungus and cuticle inflammation in 10 patients suffering from nail fungus and cuticle inflammation. The nail was roughened initially with a nail file and thereafter every three days during treatment. The salve/ointment N composition was applied on the nail every three days. A bandage was held over the nail. N 25 First the odor disappeared. The inflammation of the cuticle improved within two weeks and

QA ? after a few months the nail fungus was significantly improved.

NN

I = Example 9 treating athelete's foot

NN S The resin salve composition was manufactured according to the invention.

LO = 30 The resin salve/ointment composition was used in a method for treating athlete s foot in

O N 10 patients. The ointment was applied to the inflamed area between the toes twice a week.

The toe space was protected with a bandage. Redness, itching, flaking, and odor disappeared, and new healthy skin formed within four weeks. Example 10 treating wound, skin and coronet band damage in horses The resin salve composition was manufactured according to the invention. The product was used in a method for treating of wound, skin and coronet band damage in horses without any other supportive treatment to determine the efficacy of the product. The tolerability of the product was good according to the veterinarians. In the treatment of wounds, especially in the bruise injuries of the lower limbs, good results were obtained. The product quickly relieved the amount of inflammatory secretion and seemed to prevent excessive granulation tissue formation, which easily occurs in the wounds of horses. Recovery and healing were faster than with antibiotics. The horses were more alert and could be exercised during treatment. The product also did not cause a time of competitive restriction for competitions.

Example 11 treating acute dermatitis The resin salve composition was manufactured according to the invention. The product was used in a method for treating a common painful and moist superficial acute dermatitis, namely hot spot, in dogs. Hair was removed from and around the inflamed pelvic area. The area was cleaned, and the ointment was applied to the area twice a day once in the morning and once in the evening. A collar was fitted to the dog. The product quickly relieved redness, pain and the amount of inflammatory secretions. Good results were obtained following the one-week treatment period. N 25 Example 12 treating papulopustular acne N The resin salve composition was manufactured according to the invention. S The salve/ointment product was tested for the treatment of wet pimple acne ™~ (papulopustular acne) on the cheeks and forehead of 15 teenagers. The product was Ek applied once a day to cleansed skin. Inflammation caused by bacteria and yeasts in the N 30 skin subsided with regular use during one month.

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D S Example 13 treating seborrheic eczema N The resin salve composition was manufactured according to the invention. The salve/ointment composition was used in a method for treating sebum rash (seborrheic eczema) in five persons. The product was applied to the cleansed area of the scalp and eyebrows twice a day, once in the morning and evening. Itching, flaking, and stinging were relieved as early as following one week of regular use. Example 14 treating skin psoriasis The resin salve composition was manufactured according to the invention.

The product was tested in a method for treating skin psoriasis on the forearm and elbow of 10 patients. The product was applied twice a day, in the morning and evening, to a cleansed skin. The soothing effect on the skin was already visible following one day of treatment. The product reduced dryness, itching and flaking of the rash.

Example 15 treating burns The resin salve composition was manufactured according to the invention. The ointment was used in a method for treating hot water-induced burns in two persons.

Said salve/ointment composition was applied three times a day to the fingers and a bandage was applied over the greased area. Good results were seen followed by one week of treatment. The salve/ointment removed the pain and stinging in just a few minutes after application. A few blisters appeared on the fingers, but no inflammation.

The ointment was also applied to sun-burned skin three times a day during the acute phase in eight persons. The pain quickly disappeared, the skin calmed down, the redness and blisters disappeared within a few days. Exfoliative skin was oiled twice a day, and good results were obtained following two days of treatment.

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Claims

1. A method for manufacturing a salve composition comprising coniferous resin acids (82), characterized in that the method comprises providing a resin acid fraction (10); dissolving the resin acid fraction (10) into ethanol (20) at temperature of 50 to 70 °C, preferably at 65 °C until clear solution is obtained, wherein the resin acid fraction (10) comprises at least 70 wt-% of resin acids of which 4-10 wt-%, preferably 6 — 8 wt-% of palustric acid to provide a resin solution (30); concentrating the obtained resin solution (30) to provide a concentrated resin solution (40); providing a hydrogenated (50) and/or a partially hydrogenated vegetable oil (51) and a non-hydrogenated vegetable oil (60); mixing the hydrogenated (50) and/or the partially hydrogenated vegetable oil (51) with the non-hydrogenated vegetable oil (60) to form an oil base (70); mixing the concentrated resin solution (40) with the oil base (70) to provide a resin-oil mixture (80); and wherein an antioxidant(s) (90) is added to the resin solution, or to the resin-oil mixture, which resin-oil mixture is obtained by concentrating the resin solution under vacuum and mixing the concentrated resin solution (40) with the oil base (70), and that the amount of added antioxidant(s) (90) is from 0.005 to 0.15 % (w/w), preferably from N 0.01 to 0.1 % (w/w), more preferably from 0.04 to 0.06 % (w/w) of the total

O N composition.

N S

2. The method according to any one of the previous claims, characterized in that the r obtained resin-oil mixture (80) is homogenized (140). Ao a N 25

3. The method according to any one of the previous claims, characterized in that 3 resin/rosin (10) is dissolved into ethanol (20) in a ratio of 3:7, preferably 3:6, more S preferably 3:5, and most preferably 3:4 (resin:ethanol).

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4. The method according to any one of the previous claims, characterized in that the concentrating (110) of the resin solution (30) is performed by heating at temperature from about 40 °C to 80 °C, preferably from 45 °C to 75 °C, more preferably from 65 °C to 70 °C.

5. The method according to claims 1 to 4, characterized in that the concentrating 5 (110) of the resin solution (30) is performed under vacuum, at pressure that is in the range of 30 — 500 mbar, preferably at 50 to 100 mbar and at temperature from ambient (20 °C) to 60 °C, preferably from 35 °C to 45 °C, more preferably from 40 °C to 43 °C.

6. The method according to any of the previous claims, characterized in that in the salve composition comprising coniferous resin acids (82) the recovery of abietic acid vs theoretical is at least 70 %, preferably at least 75 %, more preferably = 84 %.

7. The method according to any one of the previous claims, characterized in that in the oil base (70) the amount of hydrogenated (50) and/or partially hydrogenated vegetable oil (51) is from 0.1 to 30 % (w/w), preferably from 1 to 20 % (w/w), most preferably from 5 to 10 % (w/w) based on the total weight of the salve composition.

8. The method according to any one of the previous claims, characterized in that the so obtained salve composition comprises resin acids in an amount of 0.1 to 30 wt-%, preferably 1 to 20 wt-%, more preferably 5 to 10 wt-% of the final salve composition.

9. A salve composition obtainable by the method according to any one of claims 1 to 8 characterized in that the recovery of abietic acid vs theoretical is at least 70 %, preferably at least 75 %, more preferably = 84 % in the salve composition comprising coniferous resin acids (82).

N 10. The salve composition according to claim 9, characterized in that the salve N composition comprises resin acids in an amount of 0.1 to 30 wt-%, preferably 1 to 20 = 25 wt-%, more preferably 5 to 10 wt-% of the final salve composition.

S z 11. The salve composition according to any one of claims 9 to 10, characterized in that > the antioxidant is selected from the group consisting of but not limited to dodecyl S gallate, propyl gallate, tert-butyl hydroguinone (TBHO), 2,4,5- IN trihydroxybutyrophenone (THBP), hydroxy methyl ditertiary butylphenol, butylated hydroxy anisole (BHA), and butylated hydroxytoluene (BHT), and wherein the antioxidant is used alone or in combination with antioxidant(s) selected from group consisting of but not limited to a-tocopherol, a-tocopheryl acetate (ATA), ascorbyl palmitate (AP), dodecyl gallate, propyl gallate, tert-butyl hydroquinone (TBHQ), 2,4,5- trihydroxybutyrophenone (THBP), hydroxy methyl ditertiary butylphenol, butylated hydroxy anisole (BHA), and butylated hydroxytoluene (BHT), preferably the antioxidant is butylated hydroxy anisole (BHA) alone or in combination with other antioxidants.

12. The salve composition according to any one of claims 9 to 11 for use in treating psoriasis, atopic dermatitis, skin burns, wounds, infected and non-infected, acute and chronic wounds, scalloping, skin breakdowns, pressure sores and burns, dandruff, flaking, seborrhoea, rosacea, pressure sores, eczemas, rashes, gashes, cuts, slashes, stabs, punctures, burns, scalds, lacerations, lacerated wounds, penetrating wounds, bullet wounds, contusions, ulcers, incised wounds, stretch marks, viral infections, such as herpes simplex, bacterial and/or fungal infections, dermatophytes, dermatomycosis, onychomycosis, dry skin and/or moisture poor skin in humans and animals.

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