What is Gilsonite?

Gilsonite or Natural Bitumen is a natural, resinous hydrocarbon found in the Uintah Basin in northeastern Utah. This natural asphalt is similar to a hard petroleum asphalt and is often called a natural asphalt, asphaltite, uintaite, or asphaltum. Gilsonite is soluble in aromatic and aliphatic solvents, as well as petroleum asphalt. Due to its unique compatibility, gilsonite is frequently used to harden softer petroleum products. Gilsonite in mass is a shiny, black substance similar in appearance to the mineral obsidian. It is brittle and can be easily crushed into a dark brown powder.

Gilsonite is found below the earth’s surface in vertical veins or seams that are generally between two and six feet in width, but can be as wide as 28 feet. The veins are nearly parallel to each other and are oriented in a northwest to southeast direction. They extend many miles in length and as deep as 1500 feet. The vein will show up on the surface as a thin outcropping and gradually widen as it goes deeper. Due to the narrow mining face, Gilsonite is mined by hand today, much like it was 50 or 100 years ago. The primary difference is that modern miners use pneumatic chipping hammers and mechanical hoists.

Gilsonite Powder or Natural Bitumen Powder

Gilsonite is categorized as a soluble material in oil solutions such as carbon disulphide or TCE (trichloroethylene). A major component of Gilsonite is carbon; it also contains several other elements including nitrogen and sulfur and some volatile compounds.

Gilsonite or Natural Bitumen is also known as Natural Asphalt, Asphalting, and is soluble in petroleum asphalt solvents. Gilsonite is used in the hardening of oil products and it is easily converted to powder form.Gilsonite Natural Asphalt , Natural Bitumen , Hard Asphalt or Hard Asphaltum is used as a performance-enhancing agent for asphalt mixes. Gilsonite-modified paving mixes achieve higher PG grades and incorporate perfectly into the asphalt blend with no need for high shear milling as is the case with many other modifiers. Gilsonite can partially or totally replace, or complement, the use of SBS polymers in modified asphalts at a fraction of the cost. Gilsonite-modified asphalts have higher stability, reduced deformation, reduced temperature susceptibility and increased resistance to water stripping than non-modified asphalts. Gilsonite is also used to make both solvent-based and emulsion pavement sealers with superior appearance and weathering properties

What is the difference between Gilsonite and Bitumen?

Bitumen is a general term for a group of combinatory material from heavy hydrocarbons which are flammable and are solved in aromatic and aliphatic solvent. Gilsonite is a natural hydrocarbon which is a brittle and shiny material and highly brittle in case of high purity.

Is Gilsonite flammable?

It burns easily with a brilliant flame. Insoluble in water.

Is Gilsonite a good sealer?

If you aren’t familiar with Gilsonite, it is a natural form of bitumen (the binder that holds the asphalt roads together) and has proven to be one of the best asphalt and sealer modifiers for the money.

What is the chemical composition of Gilsonite?

FTIR revealed the presence of alkane, aromatic rings, phenyl rings, alcohols, carbonyl groups, organic sulfoxides, and sulfate salts, confirming the fact that Gilsonite is composed of high molecular weight polycyclic constituents comprising of nitrogen, sulfur and oxygen heteroatoms.

Is gilsonite a bitumen?

Gilsonite is a naturally occurring bituminous asphalt and formally classified as an asphaltite bitumen

Gilsonite, a naturally occurring asphaltite bitumen, consists of a complex mixture of organic compounds. In the present study, advanced one and two dimensional solid state and solution 1H, 13C and 15N nuclear magnetic resonance (NMR) and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS) were employed to investigate its composition and structure. 13C NMR yielded a carbon aromaticity of 27%. Aromatic moieties in gilsonite were primarily single rings or small clusters of fused rings. Half of the aromatic carbons of gilsonite can be accounted for by pyrroles. 15N and 13C cross polarization-magic angle spinning (CP-MAS) NMR showed that most nitrogen in gilsonite was pyrrolic. The aromatic rings were heavily substituted with alkyl chains, as evidenced by 1Hsingle bond13C correlation spectra. Advanced solid state NMR spectral editing techniques clearly identified specific functional groups such as CCH3, CCH2, and Cdouble bondCH2 (exomethylene). 1Hsingle bond13C wideline separation (WISE) NMR helped identify mobile and non-protonated alkyl carbons. FT-ICR-MS indicated that ∼64% of calculated formulae generated by ESI were aliphatic, while only about 0.8–2.5% of formulae contained possible aromatic rings. All of the assigned formulae contained at least one heteroatom (N, O or S), indicating that ionization by ESI was selective for the polar fraction of gilsonite and potentially less reflective of the overall chemical character of gilsonite than NMR spectroscopy. By combining the information obtained from advanced NMR and ultrahigh resolution MS we propose a structural model for gilsonite as a mixture of many pyrrolic and a few fused aromatic rings highly substituted with and connected by mobile aliphatic chains.

Highlights

• Nitrogen and aromatic carbon were primarily present in the form of pyrrole rings.
• Little evidence was found for large poly-aromatic sheets.
• Ring structures were heavily substituted with (connected by) mobile alkyl chains.
• ESI-MS was selective for polar constituents, but generally confirmed key NMR results.
• A structural model is proposed that incorporates the key findings.

Is Gilsonite a mineral?

The mineral now know as Gilsonite or North American Asphaltum was discovered in the early 1860’s, but it was not until the mid-1880’s that Samuel H. Gilson began to promote it as a waterproof coating for wooden pilings, as an insulation for wire cable, and as a unique varnish.

History

The mineral now know as Gilsonite or North American Asphaltum was discovered in the early 1860’s, but it was not until the mid-1880’s that Samuel H. Gilson began to promote it as a waterproof coating for wooden pilings, as an insulation for wire cable, and as a unique varnish. Gilson’s promotion of the ore was so successful that, in 1888, he and a partner formed the first company to mine and market gilsonite on a commercial scale.

Originally, Gilsonite was sold as “Selects” and “Fines”; the low softening point ore with conchoidal fracture was known as “Selects”. The higher softening point ore with a pencillated structure was known as “Fines”. Selects commanded a higher price than Fines because of its better purity, good solubility, and usefulness in the paint, stain, and varnish industries.

Time and technology have changed this classification system. Processing of Gilsonite now removes most of the inert contaminants and newer, more powerful, solvents make the higher softening point grades more interesting to the user. Today, Gilsonite is graded by softening point (a rough measure of solubility) and particle size. All grades carry a degree of quality far superior to those first small amounts of crude Gilsonite marketed in the 1880’s.

What is the other name of Gilsonite

Asphaltite (also known as uintahite, asphaltum, gilsonite or oil sands) is a naturally occurring soluble solid hydrocarbon, a form of asphalt (or bitumen) with a relatively high melting temperature. Its large-scale production occurs in the Uintah Basin of Utah and Colorado, United States.

What is Gilsonite powder Usages?

Gilsonite powder is a common drilling mud additive, but it also is used in asphalt paving, roofing and construction paper, paint, ink, explosive, carbon electrodes, and various fuels.

Application

Gilsonite is used in more than 160 products, primarily in dark-colored printing inks and paints, oil well drilling muds and cements, asphalt modifiers, foundry sand additives, and a wide variety of chemical products.

Gilsonite is our trademarked brand name for uintaite, a naturally occurring solid hydrocarbon used to enhance the performance of critical applicators across multiple industries, including oil and gas, ink, paint, construction, Asphalt, and foundry.

Gilsonite reserves are distributed globally, especially within basins. It has also been found on the dwarf planet Ceres and is predicted to exist on the Martian moon Phobos.

A common application of Gilsonite is in bitumen blending. This application is practised in countries such as China, India and Iran. Known as asfaltit in Turkish, it is burnt in Silopi, a coal fired power station in Turkey.

Paint-like mixtures of Gilsonite, solvents, and other additives are used to coat and seal asphalt pavements like driveways and parking lots. Gilsonite is also used as an adhesive and waterproofing agent in the manufacture of roofing felt. Addition of Gilsonite makes some paint and wood stain formulations more durable.

Polish Industry

Paint Industry

Ink Industry

Tire Industry

Adhesive Industry

Asphalt Pavement

Foundry

Drilling Fluid

Gilsonite can be used in the manufacture of paints. This material is used in paints based on bitumen. The high nitrogen content in the Natural asphalt increases tackling properties and stability against ultraviolet radiation. This product is mainly used for painting the exterior surfaces and to create acid resistance.

What is Gilsonite paint?

Gilsonite paints are used in the automotive industry as a chassis coating and coating of metal structures due to its UV resistance. This material can give useful properties to paint and coating. As this mineral is is both abrasive and chemically neutral, it has a high resistance to acids, water and chemicals.

What solvents are used in paint industry?

The most widely used aromatic hydrocarbons solvents in paint are benzene, toluene, mixed xylenes, ethylbenzene (BTEX), and high flash aromatic napthas; aliphatic hydrocarbons include hexanes, heptane, VM&P naphtha.

Ink Industry

Gilsonite Usage in Ink. Gilsonite has been used as the first wet carbon agent in black and brown inks for newspapers and magazines. High concentrations of Gilsonite have been used in newspaper printing inks. Gilsonite competes with oil-based hydrocarbon resins, phenolic resins and metal resins.

As carbon black wetting agents for black news ink and heat set and gravure ink

As a binder in wood products industry

In drilling mud fluids and oil well cementing

As asphalt modifiers

As foundry sands and casting sands additives

In cementing slurries

To insulate tanks, tubes and even molding

As a binder and additive in steel desulfurization products

To make waterproof coatings for water pipes

Asphalt driveway coat sealer

Solvent-based and emulsion pavement sealers

As a performance-enhancing agent for asphalt mixes

As an organic fuel in fireworks

For manufacture of high purity carbon electrodes in the nuclear industry

As a binder in metallurgical additives and refractories

In manufacture of con-tact and hot melt adhesives, friction products, and pipe coatings

In roofing materials primarily as an agent to lower the penetration of petroleum asphalt without aging or oxidizing the base Asphalt

In Bitumen and Asphalt production

Technical Information

The information in these pages is based on laboratory evaluation and field experience. It is correct to the best of our knowledge. Since use and application of our products are beyond our control, Ziegler Chemical & Mineral Corp. cannot be responsible for obtained results whether used alone or in combination with other products. Recommendations are made without warranty or guarantee and buyer assumes all risk and liability.

What is the density of Gilsonite?

Since the density of Gilsonite, 1.0408 g/cm3, is very near the density of vulcanized base compound A, 1.0028 g/cm3, all of the vulcanized compounds containing Gilsonite in the proportions used in this study had about the same density.

Packing

Packing of Gilsonite is according to customer demand but we recommend to choose the best possible to protect again humidity and sun. It can be 50LBS paper bag and also in big bag 1000kg & 500kg.

The particular Gilsonite oils referred to herein and used in the Examples set forth herein to illustrate the practice of this invention are designated as Gilsonite oils 1, 2, A, B, C, X, Y, and Q and are materials available from American Gilsonite Corporation, San Francisco, Calif. Each oil has unique physical characteristics such as color and viscosity. Gilsonite oil is manufactured by American Gilsonite Corporation in proprietary processes which produce the various individual Gilsonite oil products having differing physical characteristics. The available Gilsonite oils can be selected for use in this invention by one skilled in the art of drug formulation following the teachings and disclosure herein. In general, the Gilsonite oils desired for use according to this invention will usually have a viscosity in the range of about 5 to about 5000 cps. (at 25° C.), preferably about 5 to about 1000 cps. and more preferably about 5 to about 100 cps. The specific gravity of the Gilsonite oils is usually less than 1.0 and most are in the range of about 0.8 to about 0.95. Of course, the properties of the desired final pharmaceutical formulation for a desired application and function will dictate which oil is selected for each formulation. The Gilsonite oil selected for desired penetration and transport properties can be formulated into a lotion, cream, gel, or adhesive composition, or they can be formulated into liquid or spray compositions containing solvents or permeation enhancers to provide a very low viscosity composition for skin or nail application.

As indicated above, the Gilsonite oils have a range of physical properties, which allow their isolation or purification. Such properties are dictated by the composition of the oils, specifically the individual components and respective percentage composition. The various oils typically comprise one or more of the following individual components or compounds: 6, 10-dimethyl-2-undecanone; 2,6-dimethyl-2,5-heptadien-4-one; 2-butyl-1,1,3-trimethyl cyclohexane; 2,6,10,14-tetramethyl hexadecane; 1,6,7,8,9,9a-hexahydro-4-oxo 4H-pyrido-[1,2-a]pyrimidine-3-carboxylic acid ethyl ester; 2-hydroxy-4,6-dimethylpyrimidine; trans pinane; dihydroedulan; 1-pentyl-2-propyl cyclopentane; 2,3,4-trimethyl 2-cyclopentene-1-one; and, N-formyl-2-phenylpiperidine.

Preferably and conveniently, the Gilsonite oil compositions of this invention which are applied to the skin or nails are formulated with a physiologically acceptable carrier and/or a bioactive agent comprising both the Gilsonite oil and the drug. However, the Gilsonite oil per se may be applied as a pretreatment, prior to the application of the drug formulation which then absorbs the drug formulated for transport through the skin or nails. In such case, a second application of the Gilsonite oil on top of the drug formulation application may be desired for effective drug transport. In such method the pretreatment may be omitted and the drug formulation is applied first, then the Gilsonite oil or oil formulation is applied to the skin or nails. However, such in situ formulation, or multi-step applications are not preferred due to patient inconvenience and complexity. It is preferred that the compositions of this invention be formulated for single-step application. When the formulation includes a carrier, that carrier may comprise any one of conventional topical formulation bases such as those described in Remington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa.: Mack Publishing Co., 1995). An oil, lotion, solution, cream, gel, ointment, polymer, adhesive, paste, aerosol, suppository, and nebulized formulation are representative of the topical compositions of this invention. Examples of suitable topical carriers for use herein include water, alcohols and other nontoxic organic solvents, glycerin, mineral oil, silicone, petroleum jelly, lanolin, fatty acids, vegetable oils, parabens, waxes, and the like. Particularly preferred formulations herein are ointments, lotions, creams, adhesives and gels.

It is further contemplated that the Gilsonite oils may function as a carrier. An example of such a formulation is a composition comprising Gilsonite Oil and a bioactive agent. The composition is preferably formulated for topical or transdermal application, but other administrative routes such as oral or intraveneous routes, are also possible. Other pharmaceutically acceptable additives as described herein, may optionally be included in a formulation using Gilsonite oil as a carrier.

Further additives for topical formulations are well-known in the art, and may be added to the topical composition, as long as they are pharmaceutically acceptable and not deleterious to the epithelial cells or their function. Further, they should not adversely affect the epithelial penetration efficiency of the Gilsonite oil and should not cause deterioration in the stability of the composition. For example, inert fillers, anti-irritants, tackifiers, excipients, fragrances, opacifiers, antioxidants, gelling agents, stabilizers, surfactant, emollients, coloring agents, preservatives, buffering agents, other permeation enhancers, and other conventional components of transdermal delivery devices as are known in the art.

Pharmaceutical compositions comprising a Gilsonite oil allows for enhanced penetration relative to treatment with the drug formulation alone or in combination with a state of the art pretreatment formulation, such as DMSO as a pretreatment before application of the Gilsonite oil composition, as a post treatment after application of the Gilsonite oil composition, or included in and as part of the Gilsonite oil composition. Pharmaceutical formulations comprising a Gilsonite oil and a bioactive agent allow for enhanced penetration of the bioactive agent compared to a drug formulation with no Gilsonite oil or with a drug formulation comprising a state of the art penetration enhancer, such as DMSO. The penetration enhancing properties of a Gilsonite oil formulation are effective for bioactive agents, whether they are small molecules, medium molecules or large molecules.

Gilsonite derived pharmaceutical delivery compositions and methods: cosmetic applications

Pharmaceutical formulations comprising Gilsonite oil for topical or transdermal application are disclosed. Also provided are methods for transdermal administration of a bioactive agent with enhanced penetration which comprise topical administration of a composition comprising transdermally effective amount of Gilsonite oil.

The present invention provides pharmaceutical formulations comprising a Gilsonite oil and a bioactive agent for topical application for transdermal delivery of the bioactive agent. The bioactive agent is either a component of the Gilsonite oil or an agent added to the oil. Also provided are methods for transdermal administration of a bioactive agent with enhanced penetration which comprise topical administration of a composition comprising transdermally effective amount of a Gilsonite oil for transdermal delivery of the bioactive agent. As used herein “a Gilsonite oil” means a type of oil derived from uintaite materials and available from the American Gilsonite Company, San Francisco, Calif. Gilsonite oils are available in various grades having different physical properties, such as viscosity. Following the teachings of this disclosure the appropriate Gilsonite oil or oils can be selected for formulation with the desired bioactive agent and other components to provide an effective transdermal delivery system according to this invention. Gilsonite oils of different properties can be used in mixtures in this invention, but the disclosure herein is directed to using a single Gilsonite oil in each formulation in order to teach and illustrate the present invention.

In one of the composition aspects, the present invention provides a composition for topical or transdermal administration comprising a bioactive agent and a Gilsonite oil, where the bioactive agent is either a component of the Gilsonite oil or an agent added to the oil. Preferably the composition further comprises a pharmaceutically acceptable carrier, such as a conventional oil, gel, cream, ointment, lotion, adhesive, polymer, paste, or spray that may optionally contain one or more pharmaceutically acceptable additives selected from the group consisting of excipients, preservatives, antioxidants, fragrances, emulsifiers, dyes, anti-irritants and additional penetration enhancers. The bioactive agent component is present in an effective amount for the intended use, preferably at least about 0.01% by weight, preferably about 0.1% to about 50%, and the Gilsonite oil, or remainder of the Gilsonite oil where the bioactive agent is a component of the oil, is preferably present in at least about 0.01% by weight, preferably about 0.1% to about 50%. In some formulations the Gilsonite oil component can be present as the major proportion ingredient (possibly even the only ingredient besides the bioactive agent) and thus serve the functions of both the penetration enhancer and carrier or diluent.

In another of the composition aspects, the present invention provides a penetration-enhancing system comprising a Gilsonite oil and a pharmaceutically acceptable carrier, such as a conventional oil, gel, cream, ointment, lotion, adhesive, polymer, paste, or spray that may optionally contain one or more pharmaceutically acceptable additives selected from the group consisting of excipients, preservatives, antioxidants, fragrances, emulsifiers, dyes, anti-irritants, and additional penetration enhancers. The carrier component is present in at least about 0.1% by weight, preferably about 1% to about 80%, more preferable about 2% to about 50%, and the Gilsonite oil component is present in at least about 0.1% by weight, preferably about 1% to about 80%, and more preferably about 2% to about 50%. This composition of Gilsonite oil and pharmaceutically acceptable carrier provides a base material according to the present invention which can be formulated with a desired bioactive agent.

In still another of the composition aspects, the present invention provides a composition for topical or transdermal administration with enhanced penetration comprising Gilsonite oil and a bioactive agent, where bioactive agent is either a component of the Gilsonite oil or an agent added to the oil, formulated with a penetration enhancing system comprising a Gilsonite oil and a pharmaceutically acceptable carrier, such as a conventional oil, gel, cream, ointment, lotion, adhesive, polymer, paste, or spray that may optionally contain one or more pharmaceutically acceptable additives selected from the group consisting of excipients, preservatives, antioxidants, fragrances, emulsifiers, dyes, anti-irritants, and additional penetration enhancers. The Gilsonite oil-bioactive agent component and the Gilsonite oil-carrier component can each be formulated as described above, then these two components can be mixed or formulated in a weight ratio between about 1:100 and about 100:1, preferably about 10:90 to about 90:10 and more preferably about 20:80 to about 80:20.

In one of the method aspects, the present invention provides a method for enhancing the penetration of a bioactive agent through the skin or nail of a human or other animal which comprises applying to the skin or nail of the animal a composition comprising a bioactive agent and a penetration-enhancing system containing Gilsonite oil, as described herein. Similarly, the present invention provides a method for enhancing the penetration of a bioactive agent into a plant system which comprises applying to the surface or a cut opening of a plant member a composition comprising a bioactive agent and a penetration-enhancing system containing Gilsonite oil, as described herein.

In another method aspect, the present invention provides a method for delivering a bioactive agent transdermally by administering to the skin or nail of an animal a composition comprising a bioactive agent and Gilsonite oil, as described herein, and provides a method of delivering a bioactive agent into a plant system by applying to the surface or a cut opening of a plant member a composition comprising a bioactive agent and Gilsonite oil, as described herein. The methods of delivery according to this aspect of the invention include direct application of the composition, application from an applicator device, time release application from an applicator device and other methods adapted according to the disclosure herein.

In another method aspect, the present invention provides a method of making a composition for delivery of a bioactive agent comprising mixing the bioactive agent and Gilsonite oil in proportions effective to provide a composition for the desired use, as described herein. Optionally, additional penetration-enhancing additives, or other pharmaceutically acceptable additives, such as referred to above, may also be mixed with the components or the composition, as described herein.

In another aspect, the present invention provides a device comprising an applicator device, such as a patch, strip or container containing a composition comprising a Gilsonite oil and a bioactive agent and adapted for placement on the skin or nail of the animal or on a plant member and for delivering the composition.

Another aspect of the invention provides a method of making a device for administration of a bioactive agent comprising providing an applicator device adapted for placement on the skin or nail of an animal or on a plant member and incorporating into the applicator a composition comprising Gilsonite oil and a bioactive agent, as disclosed herein.

DESCRIPTION OF THE INVENTION

According to this invention, various Gilsonite oils can be used to effectively provide transdermal delivery of drugs and/or enhance the permeability of drugs through body surfaces, particularly through the skin and through fingernails and toenails. First, the following terms as used herein shall have the following meanings.

The term “topical administration” refers to the application of a pharmaceutical agent to the external surface of the skin or the mucous membranes (including the surface membranes of the nose, lungs and mouth), such that the agent crosses the external surface of the skin or mucous membrane and enters the underlying tissues. Topical administration includes application of the composition to intact skin or mucous membrane, to broken, raw or open wound of skin or mucous membrane. Topical administration of a pharmaceutical agent can result in a limited distribution of the agent to the skin and surrounding tissues or, when the agent is removed from the treatment area by the bloodstream, can result in systemic distribution of the agent. In a preferred form of topical administration, the pharmaceutical agent is delivered by transdermal delivery.

The term “transdermal delivery” refers to the diffusion of an agent across the barrier of the skin resulting from topical administration or other application of a composition. The stratum corneum acts as a barrier and few pharmaceutical agents are able to penetrate intact skin. In contrast, the epidermis and dermis are permeable to many solutes and absorption of drugs therefore occurs more readily through skin that is abraded or otherwise stripped of the stratum corneum to expose the epidermis. Transdermal delivery includes injection or other delivery through any portion of the skin or mucous membrane and absorption or permeation through the remaining portion. Absorption through intact skin can be enhanced by placing the active agent in an appropriate pharmaceutically acceptable vehicle before application to the skin. Passive topical administration may consist of applying the active agent directly to the treatment site in combination with emollients or penetration enhancers. As used herein, reference to transdermal delivery is intended to include delivery by permeation through fingernail and toenail surfaces.

The term “transmucosal delivery” refers to diffusion of an agent across the barrier of the mucosa. The epithelia acts as a barrier and many pharmaceutical agents are unable to penetrate intact mucosa. Absorption through intact mucosa can be enhanced by placing the active ingredient in a vehicle before application to the mucosa. Passive topical administration may consist of applying the active agent directly to the treatment site in combination with penetration enhancers.

Preparation and Formulation

The particular Gilsonite oils referred to herein and used in the Examples set forth herein to illustrate the practice of this invention are designated as Gilsonite oils 1, 2, A, B, C, X, Y, and Q and are materials available from American Gilsonite Corporation, San Francisco, Calif. Each oil has unique physical characteristics such as color and viscosity. Gilsonite oil is manufactured by American Gilsonite Corporation in proprietary processes which produce the various individual Gilsonite oil products having differing physical characteristics. The available Gilsonite oils can be selected for use in this invention by one skilled in the art of drug formulation following the teachings and disclosure herein. In general, the Gilsonite oils desired for use according to this invention will usually have a viscosity in the range of about 5 to about 5000 cps. (at 25° C.), preferably about 5 to about 1000 cps. and more preferably about 5 to about 100 cps. The specific gravity of the Gilsonite oils is usually less than 1.0 and most are in the range of about 0.8 to about 0.95. Of course, the properties of the desired final pharmaceutical formulation for a desired application and function will dictate which oil is selected for each formulation. The Gilsonite oil selected for desired penetration and transport properties can be formulated into a lotion, cream, gel, or adhesive composition, or they can be formulated into liquid or spray compositions containing solvents or permeation enhancers to provide a very low viscosity composition for skin or nail application.

As indicated above, the Gilsonite oils have a range of physical properties, which allow their isolation or purification. Such properties are dictated by the composition of the oils, specifically the individual components and respective percentage composition. The various oils typically comprise one or more of the following individual components or compounds: 6,10-dimethyl-2-undecanone; 2,6-dimethyl-2,5-heptadien-4-one; 2-butyl-1,1,3-trimethyl cyclohexane; 2,6,10,14-tetramethyl hexadecane; 1,6,7,8,9,9a-hexahydro-4-oxo 4H-pyrido-[1,2-a]pyrimidine-3-carboxylic acid ethyl ester; 2-hydroxy-4,6-dimethylpyrimidine; trans pinane; dihydroedulan; 1-pentyl-2-propyl cyclopentane; 2,3,4-trimethyl 2-cyclopentene-1-one; and, N-formyl-2-phenylpiperidine.

Preferably and conveniently, the Gilsonite oil compositions of this invention which are applied to the skin or nails are formulated with a physiologically acceptable carrier and/or a bioactive agent comprising both the Gilsonite oil and the drug. However, where the drug is not a component of the oil, the Gilsonite oil per se may be applied as a pretreatment, prior to the application of the drug formulation which then absorbs the drug formulated for transport through the skin or nails. In such case, a second application of the Gilsonite oil on top of the drug formulation application may be desired for effective drug transport. In such method the pretreatment may be omitted and the drug formulation is applied first, then the Gilsonite oil or oil formulation is applied to the skin or nails. However, such in situ formulation, or multi-step applications are not preferred due to patient inconvenience and complexity. It is preferred that the compositions of this invention be formulated for single-step application. When the formulation includes a carrier, that carrier may comprise any one of conventional topical formulation bases such as those described in Remington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa.: Mack Publishing Co., 1995). An oil, lotion, solution, cream, gel, ointment, polymer, adhesive, paste, aerosol, suppository, and nebulized formulation are representative of the topical compositions of this invention. Examples of suitable topical carriers for use herein include water, alcohols and other nontoxic organic solvents, glycerin, mineral oil, silicone, petroleum jelly, lanolin, fatty acids, vegetable oils, parabens, waxes, and the like. Particularly preferred formulations herein are ointments, lotions, creams, adhesives and gels.

It is further contemplated that the Gilsonite oils may function as a carrier. An example of such a formulation is a composition comprising Gilsonite Oil and a bioactive agent, where the agent is either a component of the oil or is an agent added to the oil. The composition is preferably formulated for topical or transdermal application, but other administrative routes such as oral or intraveneous routes, are also possible. Other pharmaceutically acceptable additives as described herein, may optionally be included in a formulation using Gilsonite oil as a carrier.

Further additives for topical formulations are well-known in the art, and may be added to the topical composition, as long as they are pharmaceutically acceptable and not deleterious to the epithelial cells or their function. Further, they should not adversely affect the epithelial penetration efficiency of the Gilsonite oil and should not cause deterioration in the stability of the composition. For example, inert fillers, anti-irritants, tackifiers, excipients, fragrances, opacifiers, antioxidants, gelling agents, stabilizers, surfactant, emollients, coloring agents, preservatives, buffering agents, other permeation enhancers, and other conventional components of transdermal delivery devices as are known in the art.

Other penetration-enhancing compounds are well known in the art, for example, those described in U.S. Pat. Nos. 4,424,210 and 4,316,893, the disclosures of which are incorporated by reference. Preferred penetration-enhancing compounds include 1-dodecylazacycloheptan-2-one (AZONE.RTM.) (Stoughton, Arch. Dermatol., 1982, 118), DMSO, propylene glycol, oleyl alcohol, and methylpyrrolidone. These additional penetration-enhancing compounds can be used when desired in the composition of this invention in the conventional range of from about 0.1 to about 10% and preferably about 1.0% to about 5.0% by weight of the topical composition.

The formulations of the present invention are topically applied to the body and are adapted for use in specific treatments. For example, to treat pain a formulation is prepared comprising a pain relief agent, Gilsonite oil and a suitable carrier. For another example, to treat maladies of the fingernails or toenails (e.g., fungal infections and brittleness), a formulation is prepared for transporting the bioactive agent (e.g., antifungal or bioactive component of the oil) across the nail or to the skin under the nail, Gilsonite oil and a suitable carrier. Furthermore, formulations may be prepared to treat certain problems associated with an individual’s skin (e.g., dry skin or scaliness).

Maladies of the nails include brittleness, fragility, splitting, ridging, pitting, thickened nails (i.e., onychogryphosis and pachyonychia), loss of nail luster, abnormal nail growth, and nail discoloration. Gilsonite oil formulations, where the bioactive agent is a component or components of the oil, can be used to treat such maladies. For instance, nail strength in the case of a patient having brittle nails or fragile nails may be increased by at least 10, 20, 30, 40 or even 50 percent; a patient having thickened nails may see a decrease in nail thickness of at least 10, 20, 30, 40 or 50 percent; where loss of nail luster is at issue, one can increase luster by at least 10, 20, 30, 40 or 50 percent; and, nail growth rate in a patient experiencing abnormally slow growth may be increased by at least 10, 20, 30, 40 or 50 percent.

As with maladies of the nails, skin problems are typically treated with Gilsonite oil formulations, where the bioactive agent is a component or components of the oil. For instance, skin dryness may be substantially decreased through application of the formulations, and scaliness may be either reduced or eliminated.

As discussed above, a variety of pharmaceutical formulations have been developed with varying degrees of success, that allow for transdermal treatment. It is known to those skilled in the art that, among other factors, there is a size dependence in the rate at which molecules are transported across the epithelial barrier. The flux of larger molecules across the barrier is typically lower than for small molecules. Examples 3 through 5 below demonstrate that Gilsonite oils are effective penetration enhancers for small, medium and larger molecules. Caffeine, hydrocortisone, and a series of PEG molecules, with molecular weight from 502 to 766, were chosen as model compounds for small, medium and large molecules, respectively. Results obtained with a series of PEG molecules show decreased permeation with increased molecular weight, or size, in the presence and absence of Gilsonite oils. Pretreatment with Gilsonite oils resulted in substantially greater flux for all PEG molecules studies.

Pharmaceutical compositions comprising a Gilsonite oil allows for enhanced penetration relative to treatment with the drug formulation alone or in combination with a state of the art pretreatment formulation, such as DMSO as a pretreatment before application of the Gilsonite oil composition, as a post treatment after application of the Gilsonite oil composition, or included in and as part of the Gilsonite oil composition. Pharmaceutical formulations comprising a Gilsonite oil and a bioactive agent allow for enhanced penetration of the bioactive agent compared to a drug formulation with no Gilsonite oil or with a drug formulation comprising a state of the art penetration enhancer, such as DMSO. The penetration enhancing properties of a Gilsonite oil formulation are effective for bioactive agents, whether they are small molecules, medium molecules or large molecules.

Initial screening of the Gilsonite formulations is done using conventional Transepidermal Water Loss (TEWL) tests using mice. For example, each oil sample can beapplied topically to the mice twice daily, for four days. For samples that are liquids at room temperature a sample of about 40 to about 80 μL of the oil is applied to the skin surface. For samples that are solid at room temperature a sample of about 40 to about 60 mg of the oil is applied to the skin surface. The TEWL and skin hydration are measured using techniques well known in the art using a Meeco device (Warrington, Pa.) and a Corneometer (model CM-820, Courage & Khazak, Germany), respectively.

Subsequent evaluation of Gilsonite oil formulations is done using skin penetration studies. Skin penetration studies can performed using flow-through diffusion cells (Laboratory Glass Apparatus, Berkeley, Calif.). The diffusion cells are maintained at a constant temperature using a circulating water bath. The skin is mounted on the diffusion cell with the epidermal side toward the receiver chamber. An isotonic solution is pumped through the receiver compartment at a flow rate of 3-4 mL/h using a peristaltic pump (Ismatec, Glattbrug-Zürich, Switzerland). If the outer skin surface is pretreated residual pretreatment solution is removed and the skin surface is washed

A test solution containing a suitable amount of radioactively labeled test compound can be applied to the skin surface, and the upper donor cell is then sealed with parafilm. In a positive control experiment, skin can be pretreated with dimethyl sulfoxide (DMSO) for 2 h. The receiver fluid is stirred and samples are collected at designated time intervals over a period of about 12 hours with a Retriever IV fraction collector (ISCO, Lincoln, Nebr.). Each fraction is mixed with Ready Safe®, and analyzed in a Beckman LS 5000TA liquid scintillation counter. Flux through the skin is calculated from the slope of the linear part of the cumulative amount of drug penetrated versus time curve.

While the present invention has been described with respect to preferred embodiments thereof, it will be understood that various changes and modifications will be apparent to those skilled in the art, and that it is intended that the invention encompass such changes and modifications as failing within the scope of the appended claims. The following non-limiting examples are provided to further illustrate the present invention.

Gilsonite-derived pharmaceutical delivery compositions and methods: cosmetic and nail applications

Disclosed are pharmaceutical formulations comprising gilsonite oil for topical or transdermal application. Also provided is a method for transdermal administration of a bioactive agent with enhanced penetration, including topical administration of a composition comprising a transdermally effective amount of Gilsonite oil.

SUMMARY OF THE INVENTION

The present invention provides a pharmaceutical formulation for topical application of transdermal delivery of a bioactive agent comprising Gilsonite oil and the bioactive agent. The bioactive substance is a component of gilsonite oil or a substance added to the oil. Also provided is a method of transdermal administration of the bioactive agent with enhanced penetration comprising the topical administration of a composition comprising a transdermally effective amount of Gilsonite oil for transdermal delivery of the bioactive agent. . As used herein, “gilsonite oil” refers to a type of oil derived from uinterite material and is available from the American Gilsonite Company, San Francisco, California. Gilsonite oil is available in various grades with various physical properties (eg, viscosity). In accordance with the teachings of this disclosure, a suitable gilsonite oil for a formulation containing the desired bioactive agent and other ingredients that provides an effective transdermal delivery system of the present invention can be selected. While various characteristics of gilsonite oil can be used as a mixture in the present invention, the disclosure herein provides for a single gilsonite oil in each formulation to teach and illustrate the present invention. Described for use.

In one embodiment of the composition, the invention comprises a bioactive substance and gilsonite oil, wherein the bioactive substance is a component of the gilsonite oil or a substance added to the oil. Compositions for administration are provided. Preferably, the composition further comprises one or more pharmaceutically acceptable selected from the group consisting of excipients, preservatives, antioxidants, fragrances, emulsifiers, dyes, anti-irritants and additional penetration enhancers. Pharmaceutically acceptable carriers optionally containing additives such as conventional oils, gels, creams, ointments, lotions, adhesives, polymers, basets or sprays. The bioactive agent component is present in an effective amount for the intended use, preferably at least about 0.01% by weight, preferably from about 0.1% to about 50%, and the bioactive agent is a component of gilsonite oil The other part of the gilsonite oil is preferably present at least about 0.01% by weight, preferably from about 0.1% to about 50%. In some formulations, the gilsonite oil component can be present as a major proportion component (and possibly even as the only component other than the bioactive agent), and thus penetration enhancers and carriers or diluents And can play both roles.

Gilsonite oil itself is useful as a therapeutic agent for the treatment of skin and nail disorders. Such compositions can be manufactured by those skilled in the art and administered topically, for example, as a lotion or ointment.

In another composition embodiment, the present invention is selected from the group consisting of gilsonite oil and excipients, preservatives, antioxidants, fragrances, emulsifiers, dyes, anti-irritants and additional penetration enhancers. Including a pharmaceutically acceptable carrier optionally containing one or more pharmaceutically acceptable additives such as ordinary oils, gels, creams, ointments, lotions, adhesives, polymers, basates or sprays. A penetration promoting system is provided. The carrier component is present at least about 0.1% by weight, preferably from about 1% to about 80%, more preferably from about 2% to about 50%, and the gilsonite oil component is at least about 0.1% by weight, preferably from about 1% to It is present at about 80%, more preferably from about 2% to about 50%. This composition of gilsonite oil and a pharmaceutically acceptable carrier represents the base material of the present invention that can be formulated with the desired bioactive substance.

In yet another composition embodiment, the present invention provides a composition for topical or transdermal administration with enhanced penetration comprising a gilsonite oil and a bioactive substance, wherein the bioactive substance is gilsonite oil. A component or substance added to the oil, selected from the group consisting of gilsonite oil and excipients, preservatives, antioxidants, fragrances, emulsifiers, dyes, anti-irritants and additional penetration enhancers. A pharmaceutically acceptable carrier (eg, conventional oils, gels, creams, ointments, lotions, adhesives, polymers, basets or sprays) optionally containing one or more pharmaceutically acceptable additives; A composition is provided that is formulated with a penetration enhancing system comprising: The gilsonite oil-bioactive agent component and the gilsonite oil-carrier component can each be formulated as described above, and then these two components are about 1: 100 to about 100: 1, preferably They can be mixed or formulated in a weight ratio of about 10:90 to about 90:10, more preferably about 20:80 to about 80:20.

In one of the method embodiments, the present invention provides a method for promoting the penetration of a bioactive substance through the skin or nails of a human or other animal, comprising the use of Gilsonite oil as described herein. There is provided a method comprising applying a composition comprising a penetration enhancing system and a bioactive substance to the skin or nails of the animal. Similarly, the present invention comprises applying a composition as described herein comprising a penetration enhancer system containing gilsonite oil and a bioactive substance to the surface or cutting opening of a plant part. A method for promoting the penetration of bioactive substances into plant systems.

In another method embodiment, the present invention provides transdermal delivery of a bioactive agent by administering to the skin or nail of an animal a composition comprising gilsonite oil and a bioactive agent as described herein. By applying a composition comprising gilsonite oil and a bioactive substance, as described herein, to a surface or cutting opening of a plant part. A method for delivering an active agent is provided. The delivery method of this aspect of the invention includes direct application of the composition, application from an applicator device, time release application from an applicator device, and other methods adapted in accordance with the disclosure herein. Including.

In another method embodiment, the present invention comprises mixing the bioactive agent and gilsonite oil in a ratio effective to obtain a composition for a desired application as described herein. A method for producing a bioactive agent delivery composition comprising: If desired, additional penetration enhancing additives, or other pharmaceutically acceptable additives such as those mentioned above, can be mixed with the ingredients or compositions described herein.

In another embodiment, the present invention provides a composition comprising gilsonite oil and a bioactive agent, adapted for placement on animal skin or nails or plant parts or for delivering the composition. A device comprising an applicator device (eg, patch, strip or container) containing is provided.

Another aspect of the present invention provides an applicator device adapted for placement on the skin or nail or plant part of an animal, comprising the Gilsonite oil and bioactive agent disclosed herein. There is provided a method of manufacturing a device for administration of a bioactive agent comprising including a composition comprising the applicator device.

Manufacture and formulation The specific gilsonite oils referred to herein, used in the examples described herein to illustrate the practice of the present invention, are gilsonite oils 1, 2, A, Described as B, C, X, Y and Q, materials available from American Gilsonite Corporation, San Francisco, California. Each oil has unique physical properties such as color and viscosity. Gilsonite oil is produced by the American Gilsonite Corporation by an exclusive method that produces a variety of individual gilsonite oil products having a variety of physical properties. Available gilsonite oils can be selected for use in the present invention by one of ordinary skill in the pharmaceutical arts in accordance with the teachings and disclosure herein. In general, gilsonite oils desirable for use in the present invention typically have a viscosity in the range of about 5 to about 5000 cps (25 ° C.), preferably about 5 to about 1000 cps, more preferably about 5 to about 100 cps. The specific gravity of gilsonite oil is usually less than 1.0 and most ranges from about 0.8 to about 0.95. Of course, the properties of the desired final pharmaceutical formulation for the desired use and function will determine which oil is selected for each formulation. Gilsonite oils selected for desired penetration and transport properties can be formulated into lotions, creams, gels or adhesive compositions, or they are very low for application to the skin or nails To obtain a composition of viscosity, it can be formulated into a liquid or spray composition containing a solvent or penetration enhancer.

As mentioned above, Gilsonite oil has a range of physical properties that allow its isolation or purification. Such properties are determined by the composition of the oil, in particular the individual components and the respective composition rates. These various oils typically contain one or more of the following individual components or compounds: 6,10-dimethyl-2-undecanone, 2,6-dimethyl-2,5-heptadien-4-one, 2 -Butyl-1,1,3-trimethylcyclohexane, 2,6,10,14-tetramethylhexadecane, 1,6,7,8,9,9a-hexahydro-4-oxo4H-pyrido- [1,2- a] pyrimidine-3-carboxylic acid ethyl ester, 2-hydroxy-4,6-dimethylpyrimidine, transpinane, dihydroedulan, 1-pentyl-2-propylcyclopentane, 2,3,4-trimethyl 2 -Cyclopenten-1-one and N-formyl-2-phenylpiperidine.

Preferably and conveniently, the Gilsonite oil composition of the present invention applied to the skin or nails uses a physiologically acceptable carrier and / or a bioactive substance (including both Gilsonite oil and the drug). To be formulated. However, if the drug is not a component of the oil, it is possible to apply gilsonite oil itself as a pretreatment agent before application of the drug, which is then formulated for transport through the skin or nails. Absorbs absorbed drugs. In such cases, a second application of gilsonite oil may be desired over the drug application for effective drug delivery. In such a method, it is possible to omit the pretreatment, first applying the drug, then applying gilsonite oil or oil formulation to the skin or nails. However, such in situ formulation or multi-step application is not preferred because it is inconvenient and complicated for the patient. It is preferred to formulate the composition of the present invention for one-step application. If the formulation includes a carrier, the carrier is described in a conventional topical formulation base (eg, Remington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa .: Mack Publishing Co., 1995)). Any of the above). Oils, lotions, solutions (solutions), creams, gels, ointments, polymers, adhesives, basates, aerosols, suppositories and spray formulations are representative examples of topical formulations of the present invention. Specific examples of suitable topical carriers for use in the present invention include water, alcohols and other non-toxic organic solvents, glycerin, mineral oil, silicone, petrolatum, lanolin, fatty acids, vegetable oils, parabens, waxes and the like. Particularly preferred formulations in the present invention are ointments, lotions, creams, adhesives and gels.

Furthermore, it is contemplated that gilsonite oil functions as a carrier. An example of such a formulation is a composition comprising gilsonite oil and a bioactive substance, wherein the substance is a component of the oil or a substance added to the oil. The composition is preferably formulated for topical or transdermal application, although other routes of administration are possible, for example oral or intravenous routes. In formulations using gilsonite oil as a carrier, other pharmaceutically acceptable additives as described herein may optionally be included.

Other additives for topical formulations are well known in the art and can be added to topical compositions as long as they are pharmaceutically acceptable and do not impair epithelial cells or their function. Furthermore, they should not adversely affect the epithelial penetration efficiency of gilsonite oil and should not compromise the stability of the composition. For example, inert fillers, anti-irritants, tackifiers, excipients, fragrances, opacifiers, antioxidants, gelling agents, stabilizers, surfactants, softeners, colorings known in the art Agents, preservatives, buffers, other penetration enhancers and other conventional components of transdermal delivery devices.

The formulations of the present invention are topically administered to the body and are adapted for use in specific treatments. For example, to treat pain, a formulation comprising an analgesic, gilsonite oil and a suitable carrier is preferred. In another example, a bioactive agent (eg, an antifungal or bioactive component of the oil), gilsonite, to treat fingernails or toenails diseases (eg, fungal infection and embrittlement) A formulation is prepared for transporting oil and a suitable carrier through the nail or through the skin under the nail. Furthermore, it is possible to produce a formulation for treating certain problems associated with the skin of an individual (eg, dryness or peeling of the skin).

A pharmaceutical composition comprising gilsonite oil is included in and contained in the gilsonite oil composition as a pre-treatment before application of the gilsonite oil composition or as a post-treatment after application of the gilsonite oil composition Allows enhanced penetration compared to treatment with a drug combined with a prior art pretreatment agent (eg DMSO) as part of the drug or with the drug alone. Pharmaceutical formulations comprising gilsonite oil and a bioactive substance allow enhanced penetration compared to drugs without gilsonite oil or drugs including prior art penetration enhancers (eg, DMSO). The penetration enhancement of Gilsonite oil formulations is effective for such bioactive substances, regardless of whether the bioactive substance is a small molecule, a medium molecule or a large molecule.