BE1028968B1 - Hard wax without BHT - Google Patents

Abstract

The present invention concerns hard wax, suitable for use in food and pharmaceutical industry, characterized by a low penetration value between 10 and 15 mm/10 measured according to ASTM D1321. The invention further relates to a process comprising the steps of: - Providing a paraffin, the paraffin comprising a mixture of hydrocarbons of different chain lengths, said hydrocarbons having an average chain length greater than 350 µ, the paraffin being less than 40 wt. -% of hydrocarbons having a chain length of less than 25, wherein the paraffin has a viscosity of at least 2.5 cSt at 100°C measured according to ASTM D445, wherein the paraffin contains less than 5 ppm butylhydroxytoluene (BHT), and having a microcrystalline wax, wherein the microcrystalline wax has a needle penetration value of at most 15 mm/10 according to ASTM D1321 and, intensively mixing said paraffin and said microcrystalline wax, thereby obtaining a hard wax. Finally, the invention relates to the use of said hard waxes.

Description

HARD WASH WITHOUT BHT

TECHNICAL FIELD The present invention relates to a hard without antioxidants. The present invention also relates to methods of inhibiting oxidation in petroleum-derived products. Specifically, the present invention relates to a high performance hard wax with no added antioxidants.

BACKGROUND ART A problem with the known paraffin for use in pharmaceutical application is the addition of antioxidants. Usually BHT is added as an antioxidant. This makes the paraffin more colorfast under the influence of UV light and has a longer shelf life. If topical application of a product containing such antioxidants is used chronically and/or if the product is applied to large areas of the dermis, uptake of these agents may be significant with the potential for serious systemic cytotoxic reactions. US 9 682 021 describes a stable substantially non-aqueous, non-alcoholic, non-silicone, foamable carrier compositions comprising petrolatum or mixtures thereof, at least one foaming agent, at least one propellant and with and without the addition of an active agent. These formulations use antioxidants such as BHT and BHA to extend shelf life and prevent oxidation. However, BHT can trigger allergic reactions. Furthermore, more and more consumers are looking for products with as few additives as possible. EP 1 296 652 describes a medicament for topical administration to a mammalian patient, the medicament being a tablet and comprising: a unit dose of a therapeutically effective amount of the therapeutic agent; and a pharmaceutically acceptable carrier medium, wherein the medicament is solid at ambient temperature and has a softening point from 30°C to not greater than

35°C, which is to be placed in continuous contact with an area of skin of the patient to be treated and rubbed against said area at an application pressure which does not cause significant irritation to said area, the medicament is softened or melted to allow application of the unit dose of effecting said therapeutic agent on a desired skin area of the patient within a period of time of less than 5 minutes, and wherein the carrier medium consists essentially of or consists of cocoa butter or one or more glycerides, the glycerides being monoglycerides, diglycerides or triglycerides preferably when the glycerides are glycerol esters of C8-C18 fatty acids or polyglycolyzed glycerides. A disadvantage is that this carrier medium, which comes from natural origin, oxidizes. Upon oxidation, the butter becomes rancid, which is undesirable. As a result, the carrier medium in combination with the medicament has a very limited shelf life.

US 5037655 describes a tretinoin - mineral oil - petrolatum product in which the ingredients are mixed at about 90°C, which product retains its therapeutic activity despite storage at ambient conditions without the need for an antioxidant.

A disadvantage is that this method is only suitable for tretinoin. Furthermore, the shelf life according to this method is still limited to 2 years. An additional problem is that paraffin and waxes are usually soft. There is a need for washing with a very low penetration value. The present invention aims to find a solution to at least some of the above-mentioned problems.

SUMMARY OF THE INVENTION In the first aspect, the invention relates to a hard wax according to claim 1. A hard wax is advantageous for use in various fields of application. A low concentration of antioxidants is beneficial to counteract allergic reactions and side effects. This allows the hard wax to be used in the food and pharmaceutical industry. Furthermore, side effects resulting from the repetitive ingestion or application of antioxidants such as irritation or interference with a therapeutic or chemical are also counteracted. Furthermore, this allows the hard wax to be used in combination with substances sensitive to BHT. This is particularly advantageous in case these substances are also sensitive to oxidation, which occurs regularly. This is particularly advantageous for explosives production, where rapid and effective oxidation is often necessary. However, it is important that the hard wax itself does not oxidize in the air. The hard wax prevents oxidation by shielding oxygen and oxidizing substances from the substances contained in the paraffin.

In the second aspect, the invention relates to a method according to claim 11. In the third aspect, the invention relates to the use of a hard wax according to the first aspect. In particular, the hard wax according to the first aspect can be advantageously used in the food and pharmaceutical industries, for the production of explosives and for producing formulations suitable for printing, in particular 3D printing.

Antioxidants affect chemistry. This can lead to harmful side effects for pharmaceuticals and food, explosives and 3D printing. Furthermore, a low penetration value here is very advantageous to use in these applications,

DETAILED DESCRIPTION The invention relates to hard waxes suitable for pharmaceutical use without antioxidants.

Unless otherwise defined, all terms used in the description of the invention, including technical and scientific terms, have the meaning as generally understood by those skilled in the art of the invention. For a better assessment of the description of the invention, the following terms are explicitly explained.

“A”, “the” and “the” in this document refer to both the singular and plural unless the context clearly implies otherwise. For example, “a segment” means one or more than one segment.

The terms “comprise”, “comprising”, “consist of”, “consisting of”, “include”, “contain”, “containing”, “include”, “comprising”, “contain”, “include” are synonyms and are inclusive or open terms designating the presence of the following, and which do not exclude or preclude the presence of other components, features, elements, members, steps known from or described in the art. Citing numerical intervals through the endpoints includes all integers, fractions and/or real numbers between the endpoints, including these endpoints.

The term "paraffin" as used herein is known by CAS n. 64742-51-4. These paraffins mainly consist of aliphatic alkanes, isoalkanes and cycloalkanes (including naphthenes). Paraffin usually has a translucent, white to yellow color.

The term "microcrystalline wax" as used herein is known by CAS n. 64742-60-5. Microcrystalline wax consists mainly of isoalkanes and cycloalkanes with lower amount of aliphatic alkanes. They are usually an opaque color. The melting point is typically above 75°C, significantly higher than for paraffins.

In a first aspect, the invention relates to a hard wax characterized by an ASTM D1321 needle penetration value between 10 and 15 mm/10, wherein the wax contains less than 5 ppm butylhydroxytoluene (BHT). The hard wax, as packaged, does not contain an effective amount of a antioxidant in it. Despite the absence of such an antioxidant, the product has been shown to be highly resistant to oxidation when stored under ambient conditions and without refrigeration. The high hardness, expressed in needle penetration of the wax, also promotes its shelf life. For example, oxidative substances will penetrate less quickly into such waxes.

In a preferred embodiment, the hard wax of the present invention contains up to 10 ppm sulfur, even more preferably the hard wax contains up to 9 ppm sulfur, even more preferably the hard wax contains up to 8 ppm sulfur, even more preferably the hard wax contains up to 8 ppm sulfur wax contains up to 7 ppm sulfur, even more preferably the hard wax contains up to 6 ppm sulfur, even more preferably the hard wax contains up to 5 ppm sulfur, even more preferably the hard wax contains up to 4 ppm sulfur, even more preferably contains the hard wax contains up to 3 ppm sulfur, more preferably the hard wax contains up to 2 ppm sulfur, even more preferably the hard wax contains up to 1 ppm sulfur, most preferably the hard wax contains no sulfur.

Sulfur as used in this patent includes elemental sulfur and sulfur-containing compounds.

The sum of all sulfur-containing compounds and the elemental sulfur in the product must be lower than the proposed standard.

The hard wax includes aliphatic as well as napthenic and aromatic hydrocarbons.

Although the product is hydrogenated, not all aromatic compounds are necessarily removed from the final product.

Preferably, the hard wax comprises substantially no aromatic hydrocarbons CA%. Preferably the hard wax comprises greater than 25% napthenic hydrocarbons, more preferably the hard wax comprises greater than 30% napthenic hydrocarbons, even more preferably the hard wax comprises greater than 31% napthenic hydrocarbons, even more preferably the hard wax comprises wax more than 32% napthenic hydrocarbons, more preferably the hard wax comprises more than 33% napthenic hydrocarbons, even more preferably the hard wax comprises more than 34% napthenic hydrocarbons, even more preferably the hard wax comprises more than 35% napthenic hydrocarbons.

This distribution of napthenic, aromatic and paraffinic hydrocarbons is measured according to ASTM D2140. Napthenic hydrocarbons are well suited for use in pharmacological applications.

This is partly due to low oxidation.

For example, napthenic hydrocarbons will oxidize but this oxidation propagates slowly due to the slow migration of napthenic structures in the hard wax.

Napthenic hydrocarbons, especially hydrocarbons with cyclic structures, also evaporate less quickly.

In a preferred embodiment the hard wax has a solidification point above 50°C, preferably the hard wax has a solidification point above 55°C, even more preferably the hard wax has a solidification point above 60°C, even more preferably the hard wax has was a solidification point above 62°C.

In a preferred embodiment, the hard wax has a solidification point below 85°C, preferably the hard wax has a solidification point above 80°C, even more preferably the hard wax has a solidification point above 75°C, even more preferably the hard wax has was a solidification point above 70°C.

Most preferably, the hard wax has a solidification point between 62°C and 70°C. Lower solidification points lead to less resistance to oxidation. A solidification point according to the present invention gives an optimum between oxidation resistance, shelf life and utility due to the physical properties. The solidification points as described herein are measured according to ASTM D938. In a preferred embodiment, the hard wax has a kinetic viscosity measured at 100°C greater than 2.00 mm 2 /s, preferably the hard wax has a kinetic viscosity measured at 100°C greater than 2.50 mm 2 /s, still more preferably the hard wax has a kinetic viscosity measured at 100°C greater than 5.00 mm 2 /s, even more preferably the hard wax has a kinetic viscosity measured at 100°C greater than 7.50 mm 2 /s more preferably, the hard wax has a kinetic viscosity measured at 100°C greater than 10.00 mm 2 /s, most preferably the hard wax has a kinetic viscosity measured at 100°C greater than 11.00 mm 2 /s. In a preferred embodiment, the hard wax has a kinetic viscosity measured at 100°C less than 20.00 mm 2 /s, preferably the hard wax has a kinetic viscosity measured at 100°C less than 15.00 mm 2 /s, even more preferably the hard wax has a kinetic viscosity measured at 100°C less than 13.00 mm 2 /s, even more preferably the hard wax has a kinetic viscosity measured at 100°C less than 12.00 mm 2 /s. Higher kinetic viscosity leads to higher propagation of oxidation when contaminated, as well as faster uptake of oxidizing and/or contaminants, so that sufficient shelf life without antioxidants cannot be guaranteed. Lower kinetic viscosity results in a product that is difficult to handle, requiring significantly more energy to blend, package and manufacture the product. Kinetic viscosity is measured according to ASTM D445.

In a preferred embodiment the hard wax has a drop point or drop point greater than 50.0°C, preferably the hard wax has a drop point or drop point greater than 55.0°C, even more preferably the hard wax has a drop point or drop point greater than 60.0°C, more preferably the hard wax has a drop point or drop point greater than 61.0°C, even more preferably the hard wax has a drop point or drop point greater than 62.0°C, even more preferably the hard wax has a drop point or drop point greater than 63.0°C, even more preferably the hard wax has a drop point or drop point greater than 64.0°C. In a preferred embodiment the hard wax has a drop point or drop point less than 90.0°C, preferably the hard wax has a drop point or drop point less than 85.0°C, even more preferably the hard wax has a drop point or drop point less than 80.0°C, more preferably the hard wax has a drop point or drop point less than 75.0°C, even more preferably the hard wax has a drop point or drop point less than 74.0°C, even more preferably the hard wax has a drop point or drop point less than 73.0°C, most preferably the hard wax has a drop point or drop point less than 72.0°C.

Both a higher and a lower drop point leads to faster oxidation of the hard wax. The drop point, at a constant viscosity, is related to the degree of branching, cyclic hydrocarbons and aromatic hydrocarbons in the soft, white petrolatum. These substances, in particular aromatic hydrocarbons, influence the resistance to oxidation under the influence of visible light and UV-light. light. The drop point or drop point is measured in accordance with ASTM D127.

The bullet penetration gives sufficient hardness. Furthermore, the hardness of paraffin is related to the diffusivity of substances through this paraffin. By limiting the diffusivity of impurities through the paraffin, the propagation of oxidation is prevented. Thus, even if the top layer oxidizes, for example under the influence of UV light and air, the oxidation will remain limited to the top layer. With a bullet penetration that is high, the oxidation will quickly propagate through the material. Bullet penetration is measured in accordance with ASTM D127.

The hard wax according to the present invention should meet the quality requirements for hard wax according to the European Pharmacopoeia (Ph. Eur) edition 9. Preferably it also meets the quality requirements of the latest edition of the European Pharmacopoeia (Ph. Eur). This is necessary for commercial use in Europe. This also has various technical consequences, such as strict conditions on purity and composition.

The hard wax of the present invention must meet the hard wax quality requirements of FDA 21 CFR 172.886 and FDA 21 CFR 178.3710. This is necessary for commercial use in the United States within the food and pharmaceutical industry. This also has various technical consequences, such as strict conditions on purity and composition. In a preferred embodiment, the hard wax contains less than 4 ppm BBT, more preferably the paraffin contains less than 3 ppm BHT, even more preferably the paraffin contains less than 2 ppm BHT, even more preferably the paraffin contains less than 1 ppm BHT, preferably the paraffin does not contain BHT. In a preferred embodiment, the hard wax does not comprise butyl hydroxyanisole (BHA). BHA has similar properties to BHT, and is often used as an antioxidant, whether or not in combination with BHT. BHA is advantageously excluded in the hard wax for the same and additional reasons as BHT. In a preferred embodiment, the hard wax contains no other added antioxidants. In this context, “added antioxidants” means all antioxidants that do not occur naturally in a petroleum fraction. Non-limiting examples of antioxidants include tocopherol succinate, propyl galate, butylated hydroxytoluene, and butyl hydroxyanisole, as well as a variety of flavanoids such as quercitin and rutin.

Light often speeds up an oxidation process; storing the final product in dark containers often does a lot to slow down oxidative reactions. Oxidative photolytic changes in some compounds create degradation byproducts that function to propagate or catalyze decomposition once it has started. Similar events, called auto-oxidation, can occur even in the absence of light when sensitive materials are stored in the presence of air. The oxygen concentration of formulations (versus atmospheric oxygen) is in many cases a critical factor and often depends on the storage temperature. Oxygen becomes more soluble in aqueous media as the temperature is lowered. Thus, oxygen dependent oxidative reactions can sometimes proceed faster at lower temperatures, Decomposition by oxidation is often a complicated process, with the overall rate dependent on several factors, the relative importance of each being a function of the particular agent susceptible to oxidative degradation . The hard wax according to the present invention is only sensitive to UV light, UV light will discolor the surface of the paraffin over time. This is the result of low oxidation in this surface layer. At room temperature (below 25°C) this oxidation will be limited in the surface layer of the paraffin.

The bulk of the paraffin remains stable due to the low diffusion through the material at this temperature.

The hard wax of the present invention has a very long shelf life at room temperature.

Freezing also has little or no adverse effect on the quality of the product.

However, storage at high temperatures, such as above 30°C, can cause color and odor problems. The shelf life is at least 5 years at room temperature and in the absence of humidity.

Preferably, the shelf life is higher than 6 years.

Even more preferably, the shelf life is greater than 7 years.

Shelf life is defined as the period during which the hard wax specifications are met.

These specifications include the Ph.

EUR. edition 9 standards.

Furthermore, it is necessary that the kinematic viscosity at 100°C, the saybolt color and the bullet penetration remain within a tolerance of 15 .

Preferably within a tolerance of 10%. Even more preferably within a tolerance of 5%. In a second aspect, the invention comprises a method of producing a hard wax according to the first aspect comprising the steps of:

- Providing a paraffin, wherein the paraffin comprises a mixture of hydrocarbons of different chain lengths, said hydrocarbons having an average chain length greater than 350 µ, wherein the paraffin comprises less than 40% by weight of hydrocarbons having a chain length less than 25, wherein the paraffin has a viscosity of at least 2.5 cSt at 100°C measured according to ASTM D445, wherein the paraffin contains less than 5 ppm butylhydroxytoluene (BHT), and - Providing a microcrystalline wax, wherein the microcrystalline wax has a needle penetration value of at most 15 mm/10 according to ASTM D1321 and, - Intensively mixing said paraffin and said microcrystalline wax, thereby obtaining a hard wax.

Mixing in a microcrystalline wax and a paraffin according to the present invention results in a stable, very hard wax with a low penetration value and high oxidative resistance without the addition of antioxidants.

In a preferred embodiment, the paraffin is a petroleum derivative.

Unlike Fischer-Tropsch derivatives, petroleum derivatives generally contain more impurities, including nitrogen and sulfur components.

These impurities are only allowed in very low amounts in the hard wax for use in pharmaceutical paraffin.

Sulfur components are natural antioxidants, but still not desirable in the current composition.

In a further preferred embodiment, the paraffin is hydrogenated.

Hydrogenation is a process for removing the contaminants, such as heteroatoms (i.e., sulfur, nitrogen, oxygen) or compounds containing sulfur, nitrogen, or oxygen, from a hydrocarbon product mixture.

Conventional hydrogenation processes vary over a wide range.

In general, the total LHSV (liquid hourly space velocity) is about 0.25 to 2.0 hours, preferably about 0.5 to 1.0 hours. The hydrogen partial pressure is greater than 200 psia and is preferably about 500 psia. psia to about 2000 psia.

Hydrogen recirculation rates are usually above 50 SCF/BbI and are preferably between 1000 and 5000 SCF/Bbl.

Strong hydrogenation allows to remove impurities, heteroatoms including N, S and P as well as aromatics and unsaturated hydrocarbons.

This is extremely desirable for obtaining a hard wax according to the present invention, in particular for obtaining a wax with sufficient oxidative resistance without the addition of antioxidants.

In a preferred embodiment, the hard wax has a color as measured by the Saybolt color scale of +20 or higher, preferably +22 or higher, more preferably +24 or higher, more preferably +26 or higher, more preferably preferably +28 or higher, preferably +30 or higher.

The color not only looks white and clear, but also reflects a degree of purity.

A higher value on the saybolt color scale indicates a high level of hydrocarbons with few impurities.

In a further preferred embodiment, the paraffin has an average chain length of greater than 500 µ.

In a further preferred embodiment, the paraffin comprises less than 5% by weight of hydrocarbons having a chain length of less than 25.

In a further preferred embodiment, the paraffin has a viscosity of at least 11 cSt at 100°C measured according to ASTM D445,

In a preferred embodiment, the paraffin has an average chain length of greater than 500 µ, comprises less than 5% by weight of hydrocarbons with a chain length of less than 25 and has a viscosity of at least 11 cSt at 100°C measured according to ASTM D445.

In a third aspect, the invention includes the use of a hard wax according to the first aspect. In a preferred embodiment, a hard wax according to the first aspect is used in the food or pharmaceutical industry. More preferably, the hard wax of the present invention can be used in chewing gum. Regular paraffins with CAS 64742-51-4 may no longer be used for chewing gum according to EU Regulation 231/2012 regarding food additions. Only high-grade waxes with PM Ref no. 95859 may be used. The hard wax according to the present invention can be advantageously used in chewing gum. Furthermore, the high hardness allows prolonged chewing. In the pharmaceutical industry, therapeutic substances can be stored without the addition of chemicals that are difficult or impossible to separate, and may not be desirable for the patient's body. Saving on antioxidants is ecologically, economically and medically beneficial. The therapeutic substances can be stored at room temperature for a long time without any problems. UV light and humidity are preferably avoided. Heating above room temperature and oxygen is also preferably avoided. UV light and oxygen mainly affect the surface layer of the paraffin, without the oxidation penetrating deep into the paraffin. Thus, even in the environment of oxygen and UV light, the therapeutic substance can maintain its effect, since only a very small amount oxidizes. In a preferred embodiment, a hard wax according to the first aspect is used for explosives. In explosives, high shelf life, very low penetration value, no contaminants and no antioxidants are necessary to ensure proper operation and safety.

In a preferred embodiment, a hard wax according to the first aspect is used for printing, especially 3D printing. With 3D printing, the hard wax can be advantageously combined with powder formulations and/or they are part of powder formulations. Resistant to antioxidants and high hardness are both necessary to obtain a consistently desired print result, regardless of the color and additional additives. The addition of known antioxidants influences, among other things, the color and adhesion obtained. The use of low penetration values leads to problems controlling printhead emissions, especially during extended 3D printing where the device typically warms up. In what follows, the invention is described by reference to: non-limiting examples illustrating the invention, and which are not intended or should be interpreted to limit the scope of the invention.

EXAMPLES EXAMPLE 1: A highly refined and hydrogenated oil fraction was produced and purified to paraffin. This paraffin has less than 5 ppm sulfur. No BHT or BHA nor other antioxidants were added. Neither BHT nor BHA was measurable by GC-MS analysis with detection limit of 1 ppm. The concentration of BHT and BHA was thus lower than 1 ppm. The paraffin has an average molecular weight of 531u, a kinematic viscosity of 12.6 mm?/s, a needle penetration of 13.2 mm/10 and 3.5 wt% hydrocarbons with a chain length of less than 25.

The paraffin is intensively mixed with a microcrystalline wax with a needle penetration value of 14.3 mm/10, whereby a hard wax is obtained. The hard wax meets the Ph. EUR. Edition 9 quality standards as well as to USP 36 / NF 31. The paraffin was tested for shelf life at 15°C in dry, dark conditions. During 24 months no oxidation or discoloration was observed.

The paraffin was tested for shelf life at 25°C in dry, dark conditions.

During 36 months no oxidation or discoloration was observed.

The paraffin was tested for shelf life at 35°C in dry, dark conditions.

After

36 months still no discoloration of the surface layer was detected.

The paraffin was tested for shelf life at 25°C in dry conditions under the influence of light. After 36 months, no discoloration of the surface layer was still detected.

Claims (15)

CONCLUSIONS A hard wax characterized by an ASTM D1321 needle penetration value of between 10 and 15 mm/10, the wax containing less than 5 ppm butylhydroxytoluene (BHT). The hard wax of claim 1, wherein the wax has a pour point between 62°C and 70°C measured according to ASTM D938. A hard wax according to any one of claims 1-2, wherein the wax has an average molecular weight of 350 µ, preferably an average molecular weight of 500 µ. A hard wax according to any one of claims 1 to 3, wherein the wax comprises a mixture of hydrocarbons of different chain length, wherein the wax comprises less than 40% by weight of hydrocarbons having a chain length of less than 25. The hard wax of claim 4, wherein the wax comprises less than 5% by weight of hydrocarbons having a chain length of less than 25. A hard wax according to any one of claims 1-5, wherein the wax has a viscosity of at least 2.5 cSt at 100°C measured according to ASTM D445, The hard wax of claim 6, wherein the wax has a viscosity of at least 11 cSt at 100°C measured according to ASTM D445, A hard wax according to any one of claims 1-7, wherein the hard wax contains less than 3 ppm BHT, preferably less than 1 ppm BHT. A hard wax according to any one of claims 1-8, wherein the hard wax contains less than 5 ppm butylhydroxyanisole (BHA), preferably less than 1 ppm BHA, A hard wax according to any one of claims 1-9, wherein the hard wax contains no other added antioxidants. A method of producing a hard wax according to any one of claims 1-10, comprising the steps of: - Providing a paraffin, the paraffin comprising a mixture of hydrocarbons of different chain length, said hydrocarbons having an average chain length have greater than 350 µ, wherein the paraffin comprises less than 40% by weight of hydrocarbons having a chain length less than 25, wherein the paraffin has a viscosity of at least 2.5 cSt at 100°C measured according to ASTM D445, wherein the paraffin has less than 5 ppm butylhydroxytoluene (BHT), and - providing a microcrystalline wax, wherein the microcrystalline wax has a needle penetration value of at most 15 mm/10 according to ASTM D1321 and, - intensively mixing said paraffin and said microcrystalline wax, thereby obtaining a hard wax. A method according to claim 11, wherein the paraffin is hydrogenated, preferably intensively hydrogenated. The method of claim 11 or 12, wherein the paraffin comprises a mixture of hydrocarbons of different chain lengths, said hydrocarbons having an average chain length greater than 500 µ and wherein the paraffin is less than 5% by weight of hydrocarbons having a chain length less than 25 µm. includes. A method according to any one of claims 11-13, wherein the paraffin has a viscosity of at least 11 cSt at 100°C measured according to ASTM D445, Use of a hard wax according to any one of the preceding claims 1-10 for food, in particular chewing gum, explosives or as a substrate, in particular substrate suitable for 3D printing.