HK1137760B - Solvent addition and removal in the hydrogenation of catmint oil - Google Patents

Description

Solvent addition and removal in the hydrogenation of catmint oil

This patent application claims priority to U.S. provisional application 60/876,563 filed on 21/12/2006 and U.S. provisional application 60/876,565 filed on 21/12/2006, each of which is incorporated herein in its entirety for all purposes.

Technical Field

The invention relates to hydrogenation of essential oil of catmint plant belonging to the genus Nepeta. The hydrogenation of the essential oil provides a rich source of the insect repellent dihydronepetalactone.

Background

Dihydronepetalactone (DHN) has been shown to be an effective insect repellent as described in US 05/112,166. Dihydronepetalactones may be prepared by hydrogenation of the essential oil component nepetalactone (referred to herein as catmint oil) obtained from the plant catmint of the genus catmint. The solvent may be separated via a variety of separation methods, including steam distillation [ Regnier, f.e. et al, Phytochemistry (1967) 6: 1281-1289), organic solvent extraction, microwave-assisted organic solvent extraction, supercritical fluid extraction, mechanical extraction, and floral extraction (cold extraction first into fat, followed by organic solvent extraction) to purify catmint oil from catmint plants. The catmint oil so obtained can be used in crude form to make DHN, however, the hydrogenation reaction can be adversely affected by contaminating the undesirable components of the crude catmint oil.

Has been purified by crystallization [ Regnier, f.e. et al, Phytochemistry (1967) 6: 1271-1280] nepetalactone is purified from catmint oil, however, crystallization is expensive and, at the potential scale required for commercialization, it is uneconomical. Thus, it would be highly desirable to produce catmint oil with improved properties such that a high yield of the insect repellent DHN can be produced.

Summary of The Invention

The present invention relates to processes for preparing hydrogenated catmint oil, processes for preparing products formulated therefrom, the use of such processes, and products obtained and obtainable by such processes.

In one embodiment of the process herein, a process is provided for making hydrogenated catmint oil by (a) distilling crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the starting amount of crude catmint oil, and (ii) a pot fraction; and (b) contacting the bottoms fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil.

In another embodiment of the process herein, there is provided a process for producing hydrogenated catmint oil by (a) distilling crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the starting amount of crude catmint oil, and (ii) a pot fraction; and (b) contacting the bottoms fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; wherein one or both of steps (a) and (b) are carried out in the presence of a solvent.

In another embodiment of the processes herein, there is provided a process for making a product formulated from hydrogenated catmint oil by (a) distilling a starting amount of crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the starting amount of crude catmint oil, and (ii) a pot fraction; (b) contacting the bottoms fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and (c) incorporating the hydrogenated catmint oil produced in step (b) into a formulated product for application to the skin, hide, hair, fur, or feathers of a human or domesticated animal; wherein the distillation in step (a) and/or the hydrogenation in step (b) is carried out in the presence of a solvent.

In another embodiment of the process herein, there is provided hydrogenated catmint oil comprising 9S-dihydronepetalactone.

In another embodiment of the process herein, hydrogenated catmint oil can be prepared as follows: (a) distilling a starting amount of crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the crude catmint oil, wherein the weight of the distillate fraction is from about 2% to about 20% of the starting weight of crude catmint oil, and (ii) a pot fraction; (b) contacting the pot fraction produced in step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and (c) optionally, recovering the hydrogenated catmint oil of step (b).

In another embodiment of the process herein, hydrogenated catmint oil can be prepared as follows: (a) distilling a starting amount of crude catmint oil having at least about 150ppm of sulfur-containing compounds to produce (i) a distillate fraction comprising at least about 8 wt% of sulfur-containing compounds, based on the weight of sulfur-containing compounds in the starting amount of crude catmint oil, and (ii) a pot fraction; (b) contacting the pot fraction produced in step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and (c) optionally, recovering the hydrogenated catmint oil of step (b).

Detailed Description

The present invention relates to a process for preparing hydrogenated catmint oil, a process for preparing a product formulated therefrom, and the formulated product obtained thereby. Accordingly, an important aspect of the present invention relates to a method of treating essential oil of the catmint plant of the genus catmint (referred to herein as catmint oil). Methods of treating catmint oil include distillation and/or treatment with an oxidizing agent. The treated catmint oil so produced can be used in a hydrogenation reaction to produce hydrogenated catmint oil, which is enriched in the insect repellent dihydronepetalactone. DHN may then be used to prepare a formulated product for application to the skin, hair, fur, or feathers of a human or domestic animal.

Definition of：

In describing the methods herein, for certain terms employed in various portions of the specification, the following defined structures are provided:

the structure of the 9S-dihydronepetalactone stereoisomer is shown below.

As used herein, the term "nepetalactone" refers to a compound having the general structure of formula I:

formula I

As used herein, the term "dihydronepetalactone" ("DHN") refers to a compound having the general structure of formula II:

formula II

As used herein, the term "1-methyl-3-isopropylcyclopentanecarboxylic acid" refers to a compound having the general structure of formula III:

formula III

As used herein, the term "nepetalic acid" refers to a compound having the general structure of formula IV:

formula IV

As used herein, the term "crude catmint oil" refers to catmint oil obtained from the plant catmint of the genus catmint and comprises predominantly the trans-cis and/or cis-trans isomers of nepetalactone, as shown in formulas V and VI, respectively.

Crude catmint oil may also contain additional components such as caryophyllene, carvone, limonene, and other sesquiterpenes, as well as other unidentified impurities. One or more of these additional components can reduce the effectiveness of the catmint oil hydrogenation reaction, as measured, for example, by the rate of conversion of nepetalactone to dihydronepetalactone. The distillation step of the methods herein can facilitate removal of one or more additional components, thereby improving the hydrogenation reaction of catmint oil.

In one embodiment of the process herein, a process is provided for making hydrogenated catmint oil by (a) distilling crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the starting amount of crude catmint oil, and (ii) a pot fraction; and (b) contacting the bottoms fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil.

In one particular embodiment herein, hydrogenated catmint oil can be made as follows: (a) distilling a starting amount of crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the crude catmint oil, wherein the weight of the distillate fraction is from about 2% to about 20% of the starting weight of crude catmint oil, and (ii) a pot fraction; (b) contacting the pot fraction produced in step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and (c) optionally, recovering the hydrogenated catmint oil of step (b).

In another embodiment, the amount of the distillate fraction is from about 5% to about 10% by weight based on the starting amount of crude catmint oil.

Depending on the method used to obtain catmint oil from catmint, additional components included in catmint oil may include sulfur-containing compounds, such as dimethyl sulfide, which may reduce the rate of nepetalactone conversion by poisoning the hydrogenation catalyst. The amount of sulfur-containing compounds present in crude catmint oil can be determined using X-ray fluorescence spectroscopy.

In another embodiment herein, hydrogenated catmint oil can be prepared as follows: (a) distilling a starting amount of crude catmint oil having at least about 150ppm of sulfur-containing compounds to produce (i) a distillate fraction comprising at least about 8 wt.% of sulfur-containing compounds, based on the amount of sulfur-containing compounds in the starting amount of crude catmint oil, and (ii) a pot fraction; (b) contacting the pot fraction produced in step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and (c) optionally, recovering the hydrogenated catmint oil of step (b).

In more specific embodiments, the distillate fraction in step (a) comprises at least about 25 wt.%, at least about 50 wt.%, or at least about 75 wt.% of sulfur-containing compounds relative to the initial amount of sulfur-containing compounds in crude catmint oil.

Distillation is a well-known process [ see, e.g., "Distillation" by Seader et al, incorporated in Perry "Chemical Engineers' Handbook", 7 th edition (1997, McGraw-Hill), section 13 ]. Distillation methods suitable for use in the present process include vacuum distillation, steam distillation and solvent distillation. Both the steam distillation and the solvent distillation are optionally carried out under vacuum. Distillation of crude catmint oil can be carried out using any suitable equipment, such as a tank or resin kettle equipped with heating elements, a shell and tube condenser, and a dry ice cold finger. The temperature at which the distillation and condensation takes place will depend on the process used. For example, when a vacuum is applied during the distillation process, the heating temperature will decrease.

When steam distillation is employed, from about 2% to about 40% water (by weight relative to the weight of catmint oil plus water) may be added to catmint oil. In a more specific embodiment, from about 5% to about 20% water (by weight relative to the weight of catmint oil plus water) may be added to catmint oil. In one embodiment, the mixture of catmint oil and water can be distilled at a temperature of about 100 ℃ (i.e., the boiling point of water) at atmospheric pressure. In alternative embodiments, the distillation may be conducted at an absolute pressure of less than or equal to about 68.9 kPa. In another embodiment, the distillation may be conducted at an absolute pressure of less than or equal to about 41.4 kPa. At lower pressures, the distillation temperature decreases due to the reduced boiling point of water under reduced pressure.

Solvent distillation refers to a distillation process by which a solvent is added to facilitate separation of components in a mixture having similar boiling points. A "near boiling" mixture is one in which the components have similar boiling points. In the present invention, the solvent used is generally more volatile than catmint oil, and when evaporated, a portion of the volatile materials present in the crude oil can be removed. The solvent is preferably a compound inert to catmint oil. Solvents suitable for use in the present invention include C₁To C₅Straight or branched chain alcohols. In one embodiment, the solvent is an alcohol selected from the group consisting of methanol, ethanol, isopropanol, and n-propanol.

Preferably, the initial concentration of solvent is from about 5% to about 60% by weight relative to the total weight of catmint oil plus solvent. In another embodiment, the initial concentration of solvent is from about 10% to about 25% by weight relative to the total weight of catmint oil plus solvent. Solvent distillation may be carried out at atmospheric pressure. In alternative embodiments, the distillation may be conducted at an absolute pressure of less than or equal to about 68.9 kPa. In another embodiment, the distillation may be conducted at an absolute pressure of less than or equal to about 41.4 kPa. The temperature at which the solvent distillation is carried out depends on parameters such as the solvent used, the concentration of said solvent and the pressure at which the distillation is carried out. Typical temperatures range from about 50 ℃ to about 100 ℃.

In another embodiment of the present invention, solvent distillation may be combined with steam distillation. For example, steam distillation of crude catmint oil as described above can be carried out to obtain catmint oil from which some volatile components and most of the water have been removed. In a second distillation step, this steam distilled catmint oil is then contacted with a solvent and solvent distillation is carried out as described above. Solvent distillation will remove other volatile components that the steam distillation did not remove. In addition, solvent distillation can be used to remove residual water introduced into the catmint oil during steam distillation.

At temperatures above about 80 ℃, nepetalactone isomers in aqueous catmint oil can be hydrolyzed to undesirable products such as nepetalic acid. The rate of hydrolysis increases with temperatures up to about 200 ℃, with catmint oil thermally degrading at about 200 ℃. It is therefore desirable to be able to carry out the distillation of catmint oil at lower temperatures to avoid hydrolysis of nepetalactones. The temperature can be reduced by operating the distillation apparatus under vacuum. The degree of vacuum applied to the system will depend on the system components, however, it is preferred to achieve a vacuum of less than about 68.9kPa (abs.). In one embodiment, the vacuum distillation is conducted at an absolute pressure of less than about 6.89 kPa.

In another embodiment, the contacting step of the crude catmint oil with an oxidizing agent can be carried out prior to the distillation step as described above.

As used hereinExamples of oxidizing agents for contacting crude catmint oil include Na₂B₄O₇·10H₂O, which may be obtained, for example, from a 20MuleThe product of Borax. In one embodiment, the catmint oil can be prepared by contacting catmint oil with Na₂B₄O₇·10H₂O and then filtering the mixture to separate Na from the oxidized catmint oil₂B₄O₇·10H₂O, to make contact. In an alternative embodiment, Na may be added₂B₄O₇·10H₂O is placed in a column and crude catmint oil is allowed to drain through the column. Relative to Na₂B₄O₇·10H₂Total weight of O plus Fineleaf Schizonepeta oil, Na₂B₄O₇·10H₂O is used at a concentration of about 1 wt.% to about 50 wt.%. In more specific embodiments, relative to Na₂B₄O₇·10H₂Total weight of O plus Fineleaf Schizonepeta oil, Na₂B₄O₇·10H₂O is used at a concentration of about 3 wt% to about 50 wt%, and about 15 wt% to about 50 wt%.

Other suitable oxidizing agents for contacting crude catmint oil include hydrogen peroxide solutions used at concentrations of from about 1% to about 15% relative to the total weight of hydrogen peroxide solution plus catmint oil. A 30% hydrogen peroxide solution has been found to be suitable. The mixture of hydrogen peroxide and catmint oil was vigorously stirred, and the aqueous hydrogen peroxide phase was separated from the organic catmint oil phase. The catmint oil phase can be recovered from the aqueous hydrogen peroxide phase by decanting. Crude catmint oil and Na can be carried out at room temperature (about 25 deg.C)₂B₄O₇·10H₂O or dilute hydrogen peroxide solution.

Ozone is another alternative oxidizing agent that can be used by vigorously agitating crude catmint oil in the presence of ozone.

An example of a method of carrying out the above-described distillation and purification of crude catmint oil is described in U.S. provisional application 60/876,569, which is incorporated herein in its entirety for all purposes.

Crude catmint oil may be obtained from suppliers such as George thicker Sons (Alberta, Canada), or may be obtained from catmint plant material by known methods such as distillation [ Regnier, f.e. et al, Phytochemistry (1967) 6: 1281-1289]. One particular method of obtaining catmint oil suitable for use herein comprises the steps of: (a) contacting the plant material with steam, thereby forming a volatile heterogeneous mixture comprising catmint oil and water; (b) condensing the volatile heterogeneous mixture to form a heterogeneous liquid condensed mixture comprising catmint oil and water; (c) contacting the heterogeneous liquid condensed mixture of step (b) with sufficient salt such that the resulting mixture of (1) has [ (ρ [ ]_{Schizonepeta oil}-ρ_{Aqueous solution})/μ_{Aqueous solution}]A ratio of less than or equal to about-0.05, (2) a resulting reduction in solubility of catmint oil in the salt solution of at least about 50%, or (3) a combination of (1) plus (2), thereby causing the heterogeneous liquid condensed mixture to separate into a catmint oil phase and a brine solution phase; and (d) recovering the catmint oil phase of step (c). This process is more particularly described in U.S. provisional application 60/876,556, which is incorporated herein in its entirety for all purposes.

After distillation, and optionally contacting with an oxidizing agent, the pot fraction comprising catmint oil is used in a hydrogenation reaction to obtain hydrogenated catmint oil. The hydrogenation reaction is carried out at a temperature of about-10 ℃ to about 200 ℃ in the presence of hydrogen. The hydrogen pressure of the reaction is generally from about 0.1MPa to about 20.7 MPa. The time, temperature, hydrogen pressure and flow, and feed can be adjusted according to known principles to achieve the optimum conversion of catmint oil hydrogenation using a given catalyst. A suitable hydrogenation reaction is that described in us patent 7,067,677 (which is incorporated in its entirety as part of this document for all purposes). Described therein is the hydrogenation of nepetalactone in the presence of a catalytic metal other than nickel, platinum or palladium. The process is carried out at a temperature of from about 25 ℃ to about 250 ℃ and at a hydrogen pressure of from about 0.1MPa to about 20 MPa. Other suitable methods for preparing dihydronepetalactones include methods as described in U.S. provisional application 60/876,568, incorporated herein in its entirety for all purposes, and the hydrogenation reaction may be carried out in a batch mode in a single reactor, in a series of reactors in a sequential batch mode, in the reaction zone of one or more reactors, or in a continuous mode in any equipment commonly used for continuous processing.

In another embodiment of the present invention, the process herein provides hydrogenated catmint oil comprising 9S-dihydronepetalactone.

Particular embodiments of the processes herein include a process for making hydrogenated catmint oil by (a) distilling crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from an initial amount of crude catmint oil, and (ii) a pot fraction; (b) contacting the bottoms fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; wherein one or both of steps (a) and (b) are carried out in the presence of a solvent. Suitable solvents for one or both of the above uses include C₁To C₅Straight or branched chain alcohols, such as those selected from: methanol, ethanol, isopropanol, and n-propanol.

In the above process, the distillation in step (a) or the hydrogenation in step (b), or both, may be carried out in the presence of a solvent. Adding a solvent to the pot fraction produced in step (a) prior to hydrogenating the pot fraction in step (b), or a solvent may be present in the hydrogenated catmint oil produced in step (b), and the process further comprises the step of removing the solvent from the hydrogenated catmint oil produced in step (b). When solvent removal is performed, the process may further comprise a step of recycling the removed solvent back to the distillation of step (a) and/or the hydrogenation of step (b).

When the hydrogenation of step (b) is carried out in the presence of a solvent, it may be carried out in a plurality of steps, reactor zones or reactors, and the solvent may be removed between one step, zone or reactor and the next step, zone or reactor to follow. As mentioned above, in this case the process may further comprise the step of recycling the removed solvent back to the distillation of step (a) and/or the hydrogenation of step (b).

The above-described embodiments of the process herein can further comprise the step of incorporating the hydrogenated catmint oil produced in step (b) into a formulated product for application to the skin, hair, fur, or feathers of a human or domesticated animal.

Another alternative embodiment of the methods herein further comprises the step of incorporating hydrogenated catmint oil into a formulated product for application to the skin, hide, hair, fur, or feathers of a human or domestic animal; and generally involves the following steps:

(a) distilling a starting amount of crude catmint oil to produce (i) a distillate fraction comprising volatile components driven off from the starting amount of crude catmint oil, and (ii) a pot fraction;

(b) contacting the bottoms fraction of step (a) with hydrogen and a hydrogenation catalyst to produce hydrogenated catmint oil; and

(c) incorporating the hydrogenated catmint oil produced in step (b) into a formulated product for application to the skin, hide, hair, fur, or feathers of a human or domestic animal;

wherein the distillation of step (a) and/or the hydrogenation of step (b) is carried out in the presence of a solvent.

Solvents suitable for use in this embodiment include those described above.

This embodiment of the process may also include the step of incorporating a solvent into the formulated product, which may be accomplished by adding the solvent to the distillation that occurs during step (a), adding the solvent to the hydrogenation that occurs during step (b), or adding the solvent to both steps.

In this embodiment, incorporating the solvent into the formulated product may include any two or all three of the following steps: (i) adding a solvent to the distillation occurring in step (a), (ii) adding a solvent to the hydrogenation occurring in step (b), and (ii) adding a solvent to the hydrogenated catmint oil obtained as the product of step (b). The same solvent can be used in all steps. For example, the hydrogenation of step (b) may be carried out in multiple steps, reactor zones or reactors, and in such cases, the incorporation of solvent into the formulated product includes a step of adding solvent to some but not all, or all, of the hydrogenation that occurs within the steps, zones or reactors.

After the hydrogenation reaction, the hydrogenated catmint oil can be recovered from the reaction mixture by known separation methods such as decantation or filtration. Dihydronepetalactones can be recovered from hydrogenated catmint oil by, for example, column chromatography.

The process of distilling and hydrogenating catmint oil herein provides a hydrogenation reaction product ("HRP"). The invention also relates to compositions comprising HRP, and to the use of HRP and compositions thereof, since hydrogenated catmint oil in the form of HRP can be incorporated into formulated products for application to the skin, hair, fur, or feathers of humans or domesticated animals. The formulations of the present invention, compositions, formulations and other materials comprising the above-described HRP compounds and preparable from such compounds according to the present invention, and mixtures thereof, may be used for a variety of purposes. These include, for example, use in effective amounts as active ingredients to repel a variety of insect or arthropod species, as fragrance compounds per se, or as ingredients in fragrance compositions, or as topical treatments for the skin.

For example, the formulations herein may be applied in a topical manner to the skin, hide, hair, fur, feathers, or other surface of a mammal, such as a human or domesticated animal, that is the host of an insect or arthropod. Living hosts such as these can serve as insect-acceptable food sources for blood-sucking insects or arthropods such as biting plantlets, chiggers, fleas, mosquitoes, ticks, and white lice.

The formulations herein may also be applied to or incorporated into an inanimate host of an insect or arthropod including, for example, food sources such as growing or harvested plants or crops, or suitable living environments such as buildings or structures, or other similar protective articles such as those made from fabrics or textiles. Such inanimate hosts include, for example, turrets, silos, bins, hoppers, boxes and bags in which food products such as grains are stored, which may be a living environment or food source that is attractive to insects such as weevils or jatropha or weevils. The formulations herein are used to repel such insects by applying the formulation to a container or article, or to any inlet opening thereto.

The formulations of the invention may also be applied to human skin and/or hair as fragrance compounds per se, or as ingredients in fragrance compositions, to impart a pleasant odour or fragrance; and the formulations of the present invention may also be used as topical treatments for the skin by application to the skin and/or hair of a person in the form of body washes, cleansers, conditioners, tints, lotions, splashes, sprays or other types of cosmetic products for personal application by the user.

Insect repellent substances can drive insects or arthropods away from their preferred hosts, whether living or non-living, or render those hosts unacceptable in some way. Most insect repellents are not active poisons, but can render the desired insect/arthropod host, or the environment associated with those hosts, unattractive or offensive. Generally, an insect repellent is a formulation that can be applied topically to, on, or near a host, or can be incorporated into a host to prevent insects/arthropods from approaching or remaining near the three-dimensional space in which the host resides. In either case, the function of the repellent is to cause the insects/arthropods to repel, or repel and move away from, the host, thus minimizing the frequency of "bites" on, or the degree of injury the insects/arthropods inflict on, the living host. The insect repellent may be in gaseous (olfactory related), liquid or solid (taste related) form.

Since many insect repellents contain both polar and non-polar regions in their structure, an important characteristic for the overall efficacy of the insect repellent is surface activity. The second property is volatility. Insect repellents form a distinctive class of compounds in which volatilization of an active ingredient on or near a host surface or host contributes significantly to its efficacy as measured by protection of a living host from bites or injury.

One potential aspect of an insect repellent substance is whether the concentration of the substance in the atmospheric space above or near the surface to which it is applied is sufficient to repel an insect or arthropod, particularly a flying insect. In the air space, the desired level of insect repellent concentration can be achieved primarily through volatilization, but the rate of volatilization is affected by any surface absorption rate, so penetration into and through the surface is almost always an undesirable mode of insect repellent loss from the surface. This consideration applies equally to the loss of insect repellent by absorption to the skin or other surface of a living host, and to the loss of insect repellent from an inanimate host surface made of a free synthetic material, where the insect repellent substance can undesirably react with other chemicals present on the same surface. The loss of concentration of the repellent substance by physical action such as dilution or absorption, or by chemical action such as reaction, is also undesirable in the case of repelling reptiles/arthropods, since the concentration directly on the surface is an important factor.

Thus, in selecting a material for use as an insect/arthropod repellent active, the inherent volatility of the material is generally an important consideration. However, when it is desired to attempt to increase the persistence of the active while not decreasing and preferably increasing the volatility, various approaches may be taken. For example, the active may be formulated with a polymer and inert ingredients to increase the persistence on the surface to which it is applied or from which it will emanate. However, the presence of inert ingredients in the formulation allows the active substance in the formulation to be diluted. Thus, the loss of active due to an undesired rapid evaporation must be balanced against the risk of simply applying too little active to be effective. Alternatively, the active ingredient may be contained in microcapsules to control the rate of loss from the surface or article; precursor molecules that slowly decompose on surfaces or in articles can be used to control the release rate of the active ingredient; or a synergist may be used to continuously promote evaporation of the active from the formulation composition.

The release of an active ingredient intended for application to the skin or other surface of a living host may be achieved, for example, by sub-micron encapsulation, wherein the active ingredient is encapsulated or encapsulated in a skin-nourishing protein. The protein is used at a concentration of, for example, about 20% by weight. Insect repellent applications contain many of these protein capsules, which can be suspended in water-based lotions or water for spray applications. Upon contact with the skin, the protein capsules begin to break, releasing the encapsulated active. The process continues as each microcapsule is depleted, followed by successive replacement of a new capsule that contacts the surface and releases its active ingredient. For one application, the process may take up to 24 hours. Since proteins adhere very effectively to the skin, these formulations have a very high resistance to perspiration (reduction due to perspiration) and to the dilution by water from other sources.

A significant advantage of the formulations of the present invention is that they are all characterized by relative volatilities that make them suitable for use in obtaining the desired high concentration levels of active ingredient on, above and around the surfaces of an animate or inanimate host as described above. For this purpose, one or more of these formulations may be used in a composition as the active substance or active formulation, wherein the formulation is mixed with a carrier suitable for wet or dry application of the composition to a surface, for example, in the form of a liquid, aerosol, gel, aerogel, foam, or powder (such as a sprayable powder or dusting powder). Suitable carriers include any of a variety of commercially available organic and inorganic liquid, solid or semi-solid carrier or carrier formulations that can be used to formulate a variety of cosmetic products. When formulating a composition for application to human skin or other surfaces, it is important to select a dermatologically acceptable carrier. Suitable carriers for use herein may include water, alcohols, silicones, petrolatum, lanolin; or may include an organic liquid carrier such as a liquid aliphatic hydrocarbon (e.g., pentane, hexane, heptane, nonane, decane, and the like) or a liquid aromatic hydrocarbon.

Examples of other useful liquid hydrocarbons include oils produced by distillation of various types and grades of petrochemical feedstocks, including kerosene obtained by petroleum fractionation. Suitable petroleum oils include those commonly referred to as agricultural spray oils (e.g., so-called light and medium spray oils which consist of middle distillates in petroleum distillation and are only slightly volatile). Such oils are typically highly refined and may contain only trace amounts of unsaturated compounds. In addition, such oils are typically paraffinic oils and thus may be emulsified with water and emulsifiers, diluted to lower concentrations, and used as sprays. Tall oil from kraft cooking of wood pulp, similar to paraffin oil, can be similarly used. Other organic liquid carriers include liquid terpene hydrocarbons and terpene alcohols such as alpha pinene, dipentene, terpineol, and the like.

Other suitable carriers include silicones, petrolatum, lanolin, liquid hydrocarbons, agricultural spray oils, paraffin oils, tall oils, liquid terpene hydrocarbons and terpene alcohols, aliphatic and aromatic alcohols, esters, aldehydes, ketones, mineral oils, higher alcohols, finely divided organic and inorganic solid materials. In addition to the above-mentioned liquid hydrocarbons, the carrier may contain conventional emulsifiers which can be used to disperse the active ingredient in water and to dilute it with water for the end use. Other liquid carriers may also include organic solvents such as aliphatic and aromatic alcohols, esters, aldehydes, and ketones. Aliphatic monohydric alcohols include methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol and tert-butanol. Suitable alcohols include glycols (such as ethylene glycol and propylene glycol) and pinacol. Suitable polyhydric alcohols include glycerol, arabitol, erythritol, sorbitol, and the like. Finally, suitable cyclic alcohols include cyclopentanol and cyclohexanol.

Conventional aromatic and aliphatic esters, aldehydes and ketones can be used as carriers and sometimes in combination with the above-mentioned alcohols. Other liquid carriers also include relatively high boiling point petroleum products such as mineral oil and higher alcohols (such as cetyl alcohol). In addition, conventional or so-called "stabilizers" (e.g., dimethyl tert-butylsulfinyldithiocarbonate) may be used in conjunction with, or as a component of, one or more of the carriers used in the compositions made according to the present invention.

A variety of clays having a lamellar structure containing voids, as well as synthetic inorganic materials similar to such clays in chemical composition, crystallinity, and lamellar morphology, are suitable for use as carriers herein. Suitable clays having a lamellar structure containing voids include smectite, kaolin, muscovite, vermiculite, phlogopite, chloromagnite, and chrysotile, and mixtures thereof. Smectite clays and kaolin clays are preferred. Smectite clays include montmorillonite, beidellite, nontronite, saponite, hectorite, sauconite, and the like. Kaolin clay comprises kaolinite, dickite, nacrite, antigorite, etc. Montmorillonite is most preferred. The average particle size is in the range of 0.5 to 50 microns.

Desirable characteristics of insect/arthropod repellent compositions, particularly those applied to the skin or other surfaces of a living host, include low toxicity, resistance to loss due to water immersion or perspiration, low or no odor or at least pleasant odor, ease of application, and rapid formation of a dry, tack-free surface film. Compositions having these properties are capable of treating domesticated animals infested with insects/arthropods (e.g., flea-infested dogs, white louse-infested poultry, or biting flies or ticks-infested cattle), or humans who inevitably experience contact with insects/arthropods, by contacting the skin, hair, fur, feathers, or other surface with an amount of the composition effective to repel the insects/arthropods from the host.

Application of an effective amount of the insect repellent composition to a surface subject to insect/arthropod attack, such as the skin, bark, hair, fur, or feathers of a living host, or the stem, stalk, leaf, or flower of a plant or crop, is achieved by dispersing the insect repellent composition into the air, or by dispersing the insect repellent composition as a liquid mist or incorporated into a powder or dust and this will cause the composition to fall onto the surface of the desired host. It is also desirable to formulate insect repellent compositions by combining the formulations herein with a fugitive carrier that is applied in the form of a spray. Such compositions may be in the form of an aerosol, sprayable liquid or sprayable powder composition suitable for dispersing the active ingredient into the atmosphere by means of a compressed gas or mechanical pump sprayer. Likewise, spreading a liquid/semi-solid/solid insect repellent directly on a host in a wet or dry form (e.g., as a friable solid) is a useful method of contacting a surface of a host with an effective amount of insect repellent.

Furthermore, it is also desirable to combine the formulations herein with one or more other compounds known to have insect repellency in compositions to obtain a synergistic effect. Suitable insect repellent compounds which may be combined for this purpose include nepetalactone, nepetaamide, dihydronepetalactone and derivatives thereof, dihydronepetaamide and derivatives thereof, benzil, benzyl benzoate, 2,3, 4, 5-bis (but-2-ene) tetrahydrofurfural, polypropylene glycol monobutyl ether, N-butylacetanilide, N-butyl 6, 6-dimethyl-5, 6-dihydro-1, 4-pyrone-2-carboxylic acid N-butyl ester, dibutyl adipate, dibutyl phthalate, di-N-butyl succinate, N-diethylm-methylbenzamide, dimethyl kainate, dimethyl phthalate, 2-ethyl-2-butyl-1, 3-propanediol, 2-ethyl-1, 3-hexanediol, and mixtures thereof, The composition comprises a prophaga argyi repellent, 2-phenylcyclohexanol, p-methane-3, 8-diol and N, N-diethyl succinamic acid N-propyl ester.

The insect/arthropod repellent composition may comprise one or more essential oils and/or essential oil actives in addition to one or more of the formulations herein. Essential oils include any type of volatile oil that is derived from a plant and possesses odor and other characteristics of the plant. Examples of useful essential oils include: sweet almond oil, anise oil, basil oil, bay oil, caraway oil, cardamom oil, cedar oil, celery oil, chamomile oil, cinnamon oil, citronella oil, clove oil, coriander oil, cumin oil, dill oil, eucalyptus oil, fennel oil, ginger oil, grapefruit oil, lemon oil, lime oil, peppermint oil, parsley oil, peppermint oil, pepper oil, rose oil, spearmint oil (menthol), sweet orange oil, thyme oil, turmeric oil, and wintergreen oil. Examples of active ingredients in essential oils are: citronellal, methyl salicylate, ethyl salicylate, propyl salicylate, citronellol, safrole, and limonene.

Insects and arthropods that can be repelled by the formulations herein include any member of a large group of invertebrates whose mature form (immature insect forms include larvae and pupae) are characterized by a body that can be divided into a head, chest and abdomen, three pairs of legs, and typically (but not always) two pairs of membranous wings. This definition thus includes a variety of biting insects (e.g., ants, bees, chiggers, fleas, mosquitoes, ticks, wasps), biting flies [ e.g., blackflies, green flies, stable flies, biting flies (blood flies) ], wood-eating insects (e.g., termites), harmful insects (e.g., house flies, camphor cockroaches, white lice, cockroaches, wood lice), and household pests (e.g., flour weevils and jawberries, dust mites, moths, silverfish, weevils).

In another embodiment, the formulations herein may be used as fragrance materials, or as active materials in fragrance compositions, and may be applied topically on the skin or hair of a human or animal to impart thereto a pleasant fragrance or aroma as in colognes or perfumes for humans or pets. Alternatively, a pleasant fragrance or aroma can be obtained by using the formulations herein as insect/arthropod repellents, wherein the formulations have the dual characteristics of imparting both repellency and a pleasant fragrance or aroma.

In another embodiment, the insect/arthropod repellency and/or fragrance of products directed to other primary purposes can be improved by the presence in the product of the present formulations. Those other products include, for example, body washes, rinses, lotions, splashers, tonics or tints, bath and shower gels, foam products (e.g., shaving foams), cosmetics, deodorants, shampoos, hair gels/hair rinses, personal cleansing bar compositions (e.g., hand soaps and bath/shower soaps) or other personal care treatments or demulcents, and cleansers such as detergents and solvents, as well as air fresheners and odor removers. Such products can be processed, for example, into the form of sprayable liquids, aerosols, foams, creams, ointments, gels, pastes, powders, or friable solids. Thus, methods of processing such products include mixing the formulations herein with suitable carriers or other inert ingredients to facilitate delivery in such physical forms, such as liquid carriers that are easily sprayable; a propellant for aerosols or foams; viscous vehicles for creams, ointments, gels or pastes; or a dry or semi-solid carrier for a powder or friable solid.

Any of the above products may also contain other therapeutically or cosmetically active adjuvants or supplemental ingredients, such as those typical in the personal care industry. Examples of these include fungicides, sunscreens, vitamins, tanning agents, plant extracts, anti-inflammatory agents, antioxidants, free radical scavengers, retinoids, alpha hydroxy acids, preservatives, antibiotics, antimicrobials, antihistamines; adjuvants such as thickening agents, buffers, chelating agents, preservatives, gelling agents, stabilizers, surfactants, emollients, colorants, aloe vera, waxes, and penetration enhancers; and mixtures of any two or more thereof.

Inanimate hosts into which the formulations herein may be incorporated for insect/arthropod repellent efficacy, or to impart improved aromaticity, include articles or manufactured goods, such as textiles and fiber goods, clothing, hygiene goods, carpets, linens, outdoor or military equipment such as tents, tarpaulins, backpacks or mosquito netting, candles, paper, paint, ink, wood products such as furniture, plastics and other polymers, and the like.

The formulations herein can be formulated into compositions or incorporated into compositions for use in a biological host by any of the same methods known in the cosmetic industry, such as dilution, mixing, thickening, emulsification, pouring and pressurization. The formulations herein are incorporated into articles of manufacture for use as inanimate hosts during manufacture, by mixing, or by post-manufacture steps such as spraying or dipping.

The formulations herein may be mixed into compositions with other components, such as carriers, in amounts effective for specific purposes, such as insect/arthropod repellents, fragrances, or other skin care products. The composition will generally contain an amount of HRP as described herein of no more than about 80 weight percent based on the weight of the final product, although larger amounts may be used in certain applications and are not limited. More preferably, a suitable amount of HRP is at least about 0.001 weight percent, and preferably from about 0.01 weight percent to at most about 50 weight percent, based on the total weight of the total composition or formulated product; and more preferably from about 0.01 wt% to about 20 wt%. The particular composition will depend on the intended use.

Other compositions, materials and methods related to the use of HRP are disclosed in US 2003/062,357, US 2003/079,786, US 2003/191,047 and US 2006/148,842, each of which is incorporated in its entirety as part of this document for all purposes.

Hydrogenated catmint oil obtained by one or more methods of the present invention can be incorporated into formulated products for application to the skin, hide, hair, fur, or feathers of a human or domesticated animal; to this end, the formulated product may contain one or more adjuvants or other ingredients commonly used in the cosmetic industry, including those disclosed in U.S. patent 11/266,641 and U.S. provisional application 60/799,277, each of which is incorporated herein in its entirety for all purposes.

Where a range of numerical values is described herein, the range includes the endpoints thereof, and all the individual integers and fractions within the range, and also includes each of the narrower ranges therein formed by all the various possible combinations of those endpoints and internal integers and fractions to form subgroups of the larger group of values within the stated range to the same extent as if each of those narrower ranges were explicitly described. Where a range of numerical values is described herein as being greater than a stated value, the range is nevertheless limited and its upper limit is defined by values operable in the context of the invention as described herein. When a range of values is described herein as being less than a stated value, the range is still bounded on its lower limit by non-zero values.

In this specification, unless explicitly stated otherwise or indicated to the contrary by the context of usage, amounts, sizes, ranges, formulations, parameters and other quantities and characteristics recited herein, particularly when modified by the term "about," may be, but need not be, exact, and may also be approximate and/or larger or smaller (as desired) than the recited values to reflect tolerances, conversion factors, rounding off, measurement error and the like, and include within the specified values those values outside the specified values that have equivalent function and/or operation in the context of the present invention to the specified values.

In this specification, where an embodiment of the inventive subject matter is discussed or described as including, containing, having, encompassing, or containing certain features or elements, one or more features or elements may be present in the embodiment in addition to those explicitly discussed or described, unless explicitly stated otherwise or indicated to the contrary in the context of use. However, an alternative embodiment of the inventive subject matter may be discussed or described as consisting essentially of certain features or elements, in which embodiment features or elements that would materially alter the principle of operation or the distinguishing characteristics of the embodiment are not present therein. Another alternative embodiment of the inventive subject matter may be stated or described as consisting of certain features or elements, in which embodiment, or in insubstantial variations thereof, only the features or elements specifically stated or described are present.

Claims (12)

1. A process for making a product formulated from hydrogenated catmint oil, the process comprising:

(a) distilling a starting amount of crude catmint oil at a temperature in the range of from 50 ℃ to 100 ℃ and an absolute pressure of less than or equal to 68.9kPa to produce (i) a distillate fraction comprising volatile components driven off from the starting amount of crude catmint oil, and (ii) a pot fraction;

(b) contacting the bottoms fraction of step (a) with hydrogen, a solvent, and a hydrogenation catalyst to produce hydrogenated catmint oil; and

(c) incorporating the hydrogenated catmint oil and solvent produced in step (b) into a formulated product for application to the skin, hair, fur or feathers of a human or domestic animal;

wherein the same solvent is used in steps (b) and (c).

2. The process of claim 1, further comprising the step of adding a solvent to the distillation that occurs during step (a).

3. The process of claim 1, wherein the hydrogenation in step (b) is carried out in multiple steps, reactor zones or reactors; and the hydrogenation is carried out in the presence of a solvent in part, but not all, or in all of the steps, zones or reactors.

4. The process of claim 1, wherein the hydrogenation in step (b) is carried out in multiple steps, reactor zones or reactors; and the process further comprises the step of adding a solvent to the hydrogenation that occurs in part, but not all, or in all of the steps, zones or reactors.

5. The process of claim 1, wherein the distilling is conducted at an absolute pressure of less than or equal to 41.4 kPa.

6. The process of claim 1, wherein the distillation is conducted at an absolute pressure of less than 6.89 kPa.

7. The process of claim 1, wherein the distillation is carried out under vacuum.

8. The process of claim 1 wherein the solvent is selected from C₁To C₅Straight or branched chain alcohols.

9. The method of claim 1, wherein the solvent is ethanol.

10. The process of claim 1 wherein the distillate fraction is equal to 5 to 10 weight percent of the starting amount of crude catmint oil.

11. The process of claim 1 wherein the initial amount of crude catmint oil comprises at least 150ppm of sulfur compounds and the distillate fraction comprises at least 25 wt.% of sulfur compounds, based on the initial amount of crude catmint oil.

12. The process of claim 1 further comprising the step of contacting the crude catmint oil with an oxidizing agent prior to distillation.