GB2507639A - Pharmaceutical serum comprising an alkyl lactate and Simmondsia chinensis seed oil - Google Patents

Abstract

A pharmaceutical serum comprises (1) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chinesis seed oil, and (3) a pharmaceutical agent. Preferably, the lactate is isoamyl lactate. The pharmaceutical agent may be selected from antifungal agents, hormones, growth factors (cytokines), antimicrobials, antibacterials, antibiotics, non-steroidal anti-inflammatory agents, immunodilators, anesthetics, plant extracts, vitamins, corticosteroids, and hair growth stimulants. A hair growth stimulant may be minoxidil, retinol or retinoic acid. An anti-fungal agent may be selected from tolnaftate or undecylenic acid. The pharmaceutical agent may also be carnosic acid, such as that found in rosemary extract. Peppermint oil and tea tree oil may also be present in the serum, which may be used in the treatment of onychomycosis, or for treating hair loss. The combination of an alkyl lactate and Simmondsia chinesis seed oil may allow penetration of the pharmaceutical agent through skin, fingernails and toenails.

Description

EXCIPIENT SYSTEM FOR TOPICAL DELIVERY OF PHARMACEUTICAL AGENTS

Backround of the Invention The effectiveness of virtually all pharmaceutical compositions which are applied to the skin of a patient is normally contingent upon delivery of the active ingredients of such composition through the stratum corneum and viable epidermis into the dermis layer of the skin structure. This is because the active ingredients in such compositions cannot be effective unless they penetrate through the dead layers of skin tissue and into the dermis layer of living skin cells. This is normally a difficult proposition for water soluble active ingredients, such as ascorbic acid, because the stratum corneum is a good water barrier. The stratum corneum and viable epidermis act to protect the body by holding water therein to prevent dehydration and by keeping external water which is frequently contaminated with harmful microorganisms and toxic chemicals out of the body. By the same token, the skin is also a good barrier with respect to most organic solvents. Accordingly, only a few solvents are capable of topically delivering pharmaceutical agents deeply into the skin.

Known solvents which are capable of penetrating through the stratum corneum and viable epidermis into the dermis layer ofthe skin structure cannot be beneficially used in many cases. This is because many pharmaceutical agents are not soluble in such solvents making effective topical delivery using them impossible. Tn other cases, the solvent may by chemically or biologically incompatible with pharmaceutical agent by virtue of reacting with it or otherwise destmying its bioavailability. In still other cases, human or animal exposure to the solvent may to detrimental due to toxicity and/or undesirable side effects. For instance, the long term exposure of humans or animals to solvents, such as dimethylsulfoxide, would not be desirable and its use on a repeated basis would not normally be warranted.

In many cases, by the topical administration ofbeneficial pharmaceutical agents to treat maladies in human patients and animals or to attain other desired beneficial results is simply not possible because a solvent system for the effective delivery of the pharmaceutical agent is simply not known. In other cases, pharmaceutical agents can be delivered topically to attain beneficial results. However, the results attained could be dramatically improved if better topical delivery systems were available. For instance, hair growth stimulants, such as minoxidil, can be topically delivered with sonic degree of success. However, the level of beneficial hair growth attained could be significantly improved if a delivery system to transport the hair growth stimulant deeper into the skin structure at a higher concentration was available.

Therc has bccn a long felt nccd for an cxcipicnt system which is capable of delivering a wide range of pharniaceutical compositions through the stratum comeum and viable cpidcrmis into thc dermis layer of thc skin structure at high levels of conccntration.

Such an cxcipicint system should bc chemically and biologically inert with respect to thc pharmaceutical agent. It should also be nontoxic and should not inducc any undesirable side effects in the human patient or animal being trcated. It is also of utmost importance for thc excipient system to be a good solvent for thc pharmaceutical agent or for the pharmaceutical agcnt to be highly dispersible in it.

These has been a long felt nced for an excipient system for thc delivery of anti-fringal agents. A thngus is a member of a large group of organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushroom. These organisms are classified as a Kingdom, Fungi, which is separate from plants, animals and bacteria. Before the introduction of molecular methods for phylogenetic analysis, taxonomists considered fungi to be members of the Plant Kingdom primarily because of the similarities in lifestyle, as both fungi and plants are largely immobile, and have similarities in general morphology and growth habitat. Post molecular methods for phylogenetic analysis, the fungi have been a separate Kingdom distinct from both plants and animals, from which they appear to have diverged around one billion years ago. Advances in molecular genetics have opened the door for DNA analysis to be incorporated into taxonomy, which has oftentimes challenged the historical groupings of fungi based on morphology and other traits. Phylogenetic studies published in the last decade have helped reshape the classification of the Kingdom Fungi, which is divided into one subkingdom, seven phyla, and ten subphyla.

The fungus kingdom encompasses an enormous diversity of taxa with varied ecologies, life cycle strategies, and morphologies ranging from single-celled aquatic ehytrids to large mushrooms. However, little is known of the true diversity of Kingdom Fungi, which has been estimated at around I.5 million species, with about 5% of these having been fomully classified.

The English word fungus is directly adopted from the Latin Fungus (mushroom), used in the writings ofFloraee and Pliny. This in turn is derived from the Greek word Sphongos (Sponge), which refers to the macroscopic structures and morphology of mushrooms and molds. The discipline of biology devoted to the study of fungi is known as mycology, which is regarded as a branch of botany, even though studies havc shown that fungi are more closely related to animals than to plants.

The Kingdom Fungi includes some of the most important organisms, both in terms of their economic and ecological roles. For instance fungi by breaking down the dead organic material in the enviromnent continue the cycle ofnutrients through ecosystems.

Furthermore, most vascular plants could not grow without the symbiotic fungi that inhabit thcir roots and supply essential nutrients. Fungi has been essential in providing many breakthrough drug, such as penicillin and more sophisticated antibiotics. Other fungi have given us wonderful foods such as mushrooms, morels and the much desired truffle. From fungi we also obtain our breads, beers, and champagnes. However, with the Kingdom Fungi also conies the negative. Fungi are also responsible for a number of diseases ofboth plant (leaf, root and stem rot, rusts and smuts) and varied disease in animals and humans.

Precisely because fungi are more genetically and chemically similar to animals than any other organisms, this makes fungal diseases very difficult to treat.

Onychomycosis is a fungal infection of human fingernails or toenails.

Onychomycosis is a progressive, recurring fungal infection that initially first occurs in the nail bed and progresses to the nail plate. The main structural components ofthe nail include the lateral and proximal folds, cuticle, matrix, plate and hyponychium. The proximal nail fold is located at the proximal end of the visible nail plate where it folds over itself The horny layer of the proximal nail fold is called the cuticle. The cuticle consists of modified stratum corneum that originates at the junction of the dorsal and ventral epithelial surfuces and proceeds along the nail surface. The cuticle protects the matrix from exposure to foreign material, including infection from microorganisms. The matrix is the growth center of the nail and is located at the proximal end under the cuticle. This site contains basal cells that migrate into the nail plate, where they divide and differentiate, forming the hard, keratinized component of the nail plate. The nail plate is the largest structure ofthe nail unit and is attached to the top of the nail bed. This transparent structure is gradually replaced as it grows out. The structure is completely renewed every 6 months on fingers and every 10 to 18 months on tocs. Thc nail grows fastcr on longcr digits, digits that arc uscd most oftcn and on traumatized nails. The nail bed is located under the nail plate and consists of epidcrmal grooves and ridgcs that contain small blood vessels. The dcrmis of thc nail bordcrs bone(thc phalanx) rathcr than subcutancous tissuc.

Fungal infcctions usually invadc thc nail (between thc nail plate and thc nail bed) through an opcning in thc subungual spacc of thc hyponychium, ncar thc distal groovc. Thc infection starts distally, thcn progrcsscs proximally. Howevcr, trauma to the cuticle may also permit cntry of fungal organisms.

Thc types of microorganisms that causc onychomycosis can bc broadly classified into 2 groups: dermatophytes and nondcrmatophytcs. Dcrmatophytcs arc fungi that infcct keratinous tissue. Nondermatophytes that cause onochomycosis are either yeasts or molds.

Dermatophytes are by far the most common causative pathogens of onychomycosis.

The nail provides the perfect place for the fungus and protects it while it grows, since fungi love damp, warm, dark places, the nails of our fingers and toes are very effective barriers. This barrier makes it quite difficult for a superficial infection to invade the nail.

However, once an infection has invaded that same barrier that was so effective in protecting us against infection now works against us, making this type of flingal infection very difficult to treat.

Onychomycosis is not an uncommon disease. This type of infection accounts for approximately half of all nail disorders and one third of cutaneous ifingal infections in the United States. Studies suggest that the number ofpersons affected is apparently on the rise.

This rise maybe attributed to many factors among them the aging population. Some studies suggest that 48% of the population may bc infected by age 70. The increasingly higher occurrence of onychomyosis may also be attributable to the greater use of immunosuppressive drugs, the increasing number of people infected with HIV, the increasing exposure to pathogens in public swimming pools and spas, and high heels and tight fitting shoes in fashion styles. The growth of low cost nail salons that may not always properly disinfect nail instruments thoroughly between clients is also aftributing to the increasing occurrence of onychomycosis in many countries.

The problem with onychomycosis is aggravated by the fact that it is very contagious and casily passcd from pcrson to pcrson. In fact, many infcctcd pcoplc arc undcr thc impression that the infection will resolve spontaneously and go without any treatment while infccting othcr people. On the othcr hand, onychomycosis is notoriously difficult to treat and long treatment periods have typically been required to cure the infection using conventional drugs and techniques. It is not uncommon for patients to simply give up before that infection has been eradicated.

The dermatophyte fringus that causes the onychomycosis infection is ubiquitous. It rarely remits spontaneously and typically spreads to involve thc entire nail anatomy.

Unfortunately, onychomycosis frequently spreads to other digits, and sometimes spreads to other sites and to other family members as well as others that come in contact with the infected person or infected articles which are contaminated by the infected person.

Participants in numerous athletic activities of varied nature are much more susceptible to onychomycosis. Sonic of these athletic activities include: long distance running, ballet dancing, golf, and soccer. A wide array ofpreexisting medical conditions also leads to a higher level of susceptibility to being infected with onychomycosis. Some of these medical conditions include: diabetes mellitus, blood circulation disorders (including varicose veins in the legs, pallor of fingers and toes, and poor peripheral circulation), and genetic susceptibility associated with Down's Syndrome, Raynaud Syndrome, and Cushing's Syndrome. Cancer patients that are being treated with chemotherapy and organ transplant recipients on anti-rejection drugs are also in a high risk group.

Nail trauma is a frequent cause of onychomycosis. Individuals in trades and professions that involve the wearing of sports or safety shoes are also at higher risk. Men arc more prone to onychomycosis than women. The reasons for this gender difference arc not clear but may involve higher occurrence of nail trauma that results from professional and athletic activitics. Social and/or genetic factors may also play a role.

Nail thngus is more than just a cosmetic problem. Many people complain of discomfort in walking, pain, or limitation of their work or other activities. Gross distortion and dystrophy of the nail may cause trauma to adjacent skin and may lead to secondary bacterial infection. In several studies, patients with onochomycosis reported significantly poorer general health, mental health, social ffinctioning, and body pain than did people without this nail infection. Psychosocial limitations included fear of social situations that exposed on infected fingernail or toenail.

In immuno-eompromised people, there is a great risk that this infection will disseminate. Although onychomycosis causes some degree of morbidity for healthy individuals it is especially pronounced in high risk patients such as diabetics, patients with HIV, AIDS or other types of immunosuppressant, including transplant recipients, and patients on long term corticosteroid therapy.

Onychomycosis poses a greater risk to diabetic patients because of the possible sequelae. In particular, high risk diabetic patients with compromised lower extremities and severe neuropathy are at increased risk of developing complications from onychomycosis.

Most notably impaired sensation can make many diabetics less aware of minor abrasions and ulcerations on their feet that may be caused by trauma, from poor nail grooming or by the sharp brittle or infected nails characteristic of onychomyosis. These lesions in turn may develop into serious paronychia, cellulites or bacterial infections, and contribute to the seventy of the diabetic foot. Osteomyelitis can also result from neglected, infected nail bed erosion in diabetic patients because of the close proximity of the nail bed to the underlying bone. Nearly 18% of gangrene and 10% of foot ulcers in people can be attributed to onychomycosis. Thus, diabetics with onychomycosis should treat it quickly as it may lead to much greater, catastrophic results.

Everyone should seek treatment of a nail ffingus as soon as one is suspected.

Symptoms of nail fungus can include nail changes such as, brittleness, change in nail shape, crumbling of the outside edges of the nail, debris trapped under the nail, loosening or lifting up of the nail, loss of luster or shine, white spots, thickening of the nail or white or yellow streaks on the side of the nail. Much more rarely, a black strip or spot is present.

Current treatment for ocychomycosis include mechanical debridement, oral drugs, topical drugs, removal of nail and laser treatments. Mechanical debridement is a traditional podiatric approach that requires time, specialized instruments, and experience. The goal of this approach is to reduce pressure and fungal load by mechanically reducing nail thickness.

Since mechanical debridement removes a large portion of fungal material it has potential to enhance the effectiveness of other therapies. However, it does have its limitations. Tt does not eradicate the infectious pathogens, and it must bc repeated as the nail grows until thc infection is gone.

Oral antifungal medications arc often prescribed as first -line treatments for nail fungus. These systemic drugs reach the infected nail via the peripheral circulation. Though antifungal medications have improved it has been suggested that as many as 25% to 40% of onychomycosis cases are classified as treatment failures in clinical practice. In addition thcse oral drugs have many adverse side affects including headache, gastrointestinal symptoms such as diarrhea, dyspcpsia, abdominal pain, constipation, nausea and flatulence; dermatological symptoms such as rash, pruritus and urticaria. Additionally these oral antifungal drugs may effect the liver, therefore liver function and white cell counts should be assessed at baseline and periodically during treatment. Neutmpenia and transient taste disturbance may also result. Another downside to oral antifungal medication is the financial impact for the patient as these oral antifungal drugs can be quite expensive.

Current topical antifungal therapy is effective for the treatment of onochomycossis in some cases. This approach involves the direct application of an antifungal drug to the infected nail. These drugs are thought to diffuse through the nail plate to reach the site of infection, where they eradicate fungal organisms. These over the counter creams and ointments generally do not help treat this condition.

Removal of the nail involves the removal of the affected nail plate, this may be performed surgically or chemically. This approach allows growth of a new nail but can traumatize the nail bed, which may affect the appearance of the new naih Total nail removal causes great discomfort to the patient and therefore is discouraged. Only in the most severe cases should this method be recommended.

Practitioners have been using lasers for toenail fungus since 2009. However, podiatrists using this method disagree greatly on its effectiveness both medically and from thc standpoint of cost. The treatment consists of the practitioner aiming a laser beam at the patient's toenail to kill the organisms that cause the fungus. The nails are not immediately clear afier the treatment, which takes up to an hour and the patient must wait for the fungus free nail to grow out which cat take up to about 18 months. Multiple laser freaftnents are frequently required and the total cost of such treatments can preclude them from being a possibility for many patients. In addition to this the high cost of laser treatments is generally not covered by insurance because it is considered to be an aesthetic procedure.

Considering the problems associated with the current methods of treatment for nail fungus something more ideal needs to be found. Georgeanne Botek, DPM Department of Orthopedic Surgery at The Cleveland Clinic, suggests that the ideal anti fungal treatment would be broad spectrum, taken up and incorporated into the nail matrix, diffusing through thc epithelium of the nail bed to reach the nail bed hyperkeratosis, and penetrating into the ventral surface of the plate. Additionally, it would be effective, with high rates of clinical cure (ascertained by laboratory testing, fringal culture) and a low rate of relapsc and effective when used short term (the duration of new nail re-growth) and have few in any adverse effects and adverse drug interactions. It should also, of course, be cost effective.

Summary of thc Invention

The subject invention is based upon the discovery that a wide variety of pharmaceutical agents can be delivered into the skin, fingernails, and toenails of patients by dissolving or dispersing the pharmaceutical agent in a solvent system which is comprised of a combination of an alkyl lactate and Simmondsia chinesis seed oil. Tt is critical for the solvent system to contain both the alkyl lactate and Simmondsia chinesis seed oil to attain penetration through skin, fingernails and toenails. In other words, for effective delivery of the pharmaceutical agent through the skin or nail it is critical for the pharmaceutical agent to be dissolved or dispersed in a mixture of an alkyl lactate and Simmondsia chinesis seed oil.

The subject invention more specifically discloses a pharmaceutical serum which is comprised of (1) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chinesis seed oil, and (3) a pharmaceutical agent.

Some representative examples of pharmaceutical agent which can be incorporated into the pharmaceutical serums of this invention include, antiftingal agents, hormones, growth factors (cytokines), antimicrobials, antibacterials, antibiotics, non-steroidal anti-inflammatory agents, immunodilators, anesthetics, plant extracts, vitamins, corticosteroids, hair growth stimulants, and the like.

The subject invention more specifically discloses a pharmaceutical serum which is comprised of (1) an alkyl lactate, wherein the alkyl group in the ailcyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chinesis seed oil, and (3) a pharmaceutical agent.

The subjcct invention further discloses a pharmaceutical serum which is comprised of (1) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia ehinesis seed oil, and (3) a pharmaceutical agent, wherein the pharmaceutical agent is selected from the group consisting of antifungal agents, hormones, growth factors, antimicrobials, antibacterials, antibiotics, non-steroidal anti-inflammatory agents, immunodilators, anesthetics, plant extracts,vitanins, corticosteroids, hair growth stimulants, and the like.

In one embodiment of this invention a hair growth stimulant is included in the pharmaceutical serum of this invention as the pharmaceutical agent. In most cases the hair growth stimulant will be a antihypertensive vasodilator medication, such as minoxidil(6-(1-piperidinyl)-2,4-pyrimidinedia mine 3-oxide) which is included in the serum at a level which is within the range of about 0.5 weight percent to about 12 weight percent. The hair growth stimulant will more typically be included in the serum at a level which is within the range of about I weight percent to about 8 weight percent. The hair growth stimulant will most typically be included in the serum at a level which is within the range of about 2 weight percent to about S weight percent.

The present invention also reveals a method for treating human hair loss which comprised topically applying a hair growth serum to an area of skin where hair growth is desired, wherein the hair growth serum is comprised of (I) an ailcyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chinesis seed oil, and (3) from about 0.5 weight percent to about 12 weight percent of a hair growth stimulant.

In another embodiment of this invention an antioxidant is included in the pharmaceutical serum of this invention as the pharmaceutical agent. in most cases the -10-antioxidant, such as carnosic acid, vill be included in the pharmaceutical serum at a level which is within the range of about 0.01 weight percent to about 15 weight percent. The antioxidant will more typically be included in the serum at a level which is within the range of about 0.1 weight percent to about 12 weight percent. The antioxidant will most typically be included in the serum at a level which is within the range of about 0.5 weight percent weight percent to about I 0 weight percent.

In another embodiment of this invention (2E,4E,6E,8E)-3,7-dimcthyl-9-(2,6,6-trimethylcyclohex-l-enyl)nona-2,4,6, 8-tctraen-1-ol, commonly known as retinol, or retinoic acid, commonly known as Retin-A, is included in the pharmaceutical serum ofthis invention as the pharmaceutical agent. Rctinol and Retin-A are known to increase the production of cells in the top layer of skin, helping to rejuvenate the skin. As a result, the skin gradually looks younger in appearance. Retinol and Retin-A also induce higher levels of collagen production which makes to skin firmer and accordingly gives it a younger appearance.

Those agents rnay also reduce pigmentation issues that stern frorn sun damage. In any case retinol and Retin-A are known to help improve the overall appearance of the skin and to reduce the visible signs of aging. These agents are also highly effective antioxidants that can help prevent harmful carcinogens from breaking down skin cells. They also stimulate the production of healthy skin cells, which is essential in healing skin damage caused by aging and environmental exposure. Retinol and Retin-A also stimulates collagen production, which can help fill in the fine lines and wrinkles caused by age, shrink pores, and soften the skin.

By virtue of their ability to unclog pores and remove dead skin cells retinol and Retin-A are often used in treating patients suffering with acne. The healing pmperties of retinol can also help to reverse sun damage and relieve sunburn. Retinol and Retin-A are both derivatives of vitamin A and are sometimes used interchangeably due to conffision However, Retin-A is much stronger and has a much more aggressive effect on the skin. As a consequence of Retin-A being significantly harsher and causing a higher incidence of side effects, such as skin redness, itchiness and rashes, retinol is much better for sensitive skin.

In most cases the retinol will be included in the pharmaceutical serum at a level which is within the range of about 0.1 weight percent to about 15 weight percent. On the

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other hand, retinoic acid will typically be included in such pharmaceutical serums at levels which are in the range of about 0.005 weight percent to about 0.5 weight percent. In any case, this invention further discloses a pharmaceutical serum which is comprised of(l) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about I 2 carbon atoms, (2) Simmondsia chinesis sccd oil, and (3) a pharmaceutical agent which is selected from the group consisting ofretinol and retinoic acid.

The prcscnt invention also reveals a method for skin rejuvenation which comprised topically applying a skin rejuvenation serum to an area of skin where skin rcjuvenation is desired, wherein the skin rejuvenation serum is comprised of(1) an ailcyl lactate, wherein the alkyl group in thc alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chincsis seed oil, and (3) an effective amount of a vitamin A derivative selected from the group consisting of retinol and rctinoic acid.

Thc subjcct invention is bascd upon the discovery that an antifungal agcnt can bc delivered through the fingernail or the toenail of an infected human to treat onychomycosis by dissolving or dispersing the antifungal agent in a solvent system which is comprised of a combination of an ailcyl lactate and Simmondsia chinesis seed oil. It is critical for the solvent system to contain both the alkyl lactate and Simmondsia chinesis seed oil to attain penetration through the fingernail or the toenail. In other words, for effective delivery of the antifungal agent through the nail to reach the fungus under the nail it is critical for the antifungal agent to be dissolved or dispersed in a mixture of an alkyl lactate and Simmondsia chinesis seed oil. Accordingly, in accordance with this invention the antifungal agent is absorbed by and incorporated into the nail matrix by diffusing through the epithelium of the nail bed to reach the nail bed hyperkeratosis. The antifungal agent additionally penetrates into the ventral surface of the nail plate.

The antifungal serum of this invention has been determined to be highly effective (offers a high rate of clinical cure) and offers a low rate of relapse. Tt is also effective when used short term (the duration of new nail re-growth) and is not believed to have any adverse effects or to cause adverse drug interactions. Additionally, the antifungal serum of this invention is highly cost effective in treating onychomycosis.

The subject invention more specifically discloses an antifungal serum which is comprised of (I) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chinesis seed oil, and (3) an antifungal agent.

The present invention also reveals a method for a-eating a human fingernail or toenail which is infected with onychomycosis which comprised applying an antifungal serum to the infectcd nail, wherein thc antifungal serum is comprised of (1) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atonis, (2) Simmondsia chinesis seed oil, and (3) an antifungal agent.

Detailed Description of the Invention

The pharmaceutical serum of this invention is comprised of(l) an ailcyl lactate, (2) Simmondsia chinesis seed oil, and (3) a pharmaceutical agent. The ailcyl lactate utilized will typically have an alkyl group that contains from 2 to about 12 carbon atoms and will accordingly be of the structural formula: H3CCHCO R wherein R represents an straight chained or a branched alkyl group that contains from 2 to 12 carbon atoms. The alkyl group (R) ofthe alkyl lactate will typically contain from 2 to about 8 carbon atoms and will more typically contain from 3 to 6 carbon atoms. In many cases the alkyl group of the alkyl lactate will contain froni 4 to 6 carbon atoms. For instance, the alkyl group of the alkyl lactate can contain 4, 5, or 6 carbon atoms. Sonic representative examples of alkyl lactates that can be used include: ethyl lactate, n-propyl lactate, iso-propyl lactate, n-butyl lactate, iso-butyl lactate, t-butyl lactate, isoamyl lactate, n-pentyl lactate, t-pentyl lactate, n-hexyl lactate, iso-hexyl lactate, t-hexyl lactate, n-heptyl lactate, iso-heptyl lactate, t-heptyl lactate, n-octyl lactate, iso-octyl lactate, and t-oetyl lactate.

Isoamyl lactate is preferred for utilization as the alkyl lactate because it is not a volatile as the lower molecular weight ailcyl lactates, but is still a low viscosity liquid at room temperature. Isoamyl lactate is of the structural formula: CH3 H3C-CH--C--O CH2-0H2---CH CH3 -13-and is also a colorless liquid having a pleasant mild odor. Isoamyl lactate is preferred for utilization in conjunction with oil soluble antiffingal agents, such as undecylenic acid.

Mixtures of various alkyl lactates can be utilized in the pharmaceutical serum ofthis invention. For instance, a mixture of ethyl lactate and isoamyl lactate can be employed.

Ethyl lactate is a colorless liquid of the structural formula: OH 0 H3CCHCO CH2CH3 which is preferred for utilization in conjunction with antiftingal agents which are water soluble. However, ethyl lactate has a strong odor. Accordingly, it is preferred to utilize ethyl lactate in mixtures with a higher molecular weight ailcyl lactate to reduce volatility and the level of odor. it is desirable to utilize ethyl lactate in mixtures with isoamyl lactate in some cases. The weight ratio of ethyl lactate to isoamyl lactate will typically be within the range of about 1:10 to about 20:1. The weight ratio of ethyl lactate to isoamyl lactate will more typically be within the range of about 1:5 to about 10:1. Such mixtures of ethyl lactate and isoamyl lactate will preferably contain from about 30 weight pereent to 70 weight percent ethyl lactate and from about 30 weight percent to about 70 weight percent isoamyl lactate. Such mixtures of ethyl lactate and isoamyl lactate will more preferably contain from about 40 weight percent to 60 weight percent ethyl lactate and from about 40 weight percent to about 60 weight percent isoamyl lactate. Such mixtures of ethyl lactate and isoamyl lactate will most preferably contain from about 45 weight percent to 55 weight percent ethyl lactate and from about 45 weight percent to about 55 weight percent isoamyl lactate.

The Simmondsia chinesis seed oil used in the antiffingal serums of this invention is commonly known as jojoba oil or goat-nut oil. The Simmondsia chinesis seed oil can be expeller processed or it can be cold pressed at a temperature which does not exceed 150°F (66°C) and which preferably does not exceed 120°F (49°C). The Simmondsia ehinesis seed oil is preferably golden Simmondsia chinesis seed oil which is filtered, but which is not refined. Accordingly, the Simmondsia chinesis seed oil will normally be filtered to remove -14-undesired particulate matter. Tn some cases refined Sininiondsia chinesis seed oil can by used in the pharmaceutical serums ofthis invention with good results. Such refined Simmondsia chinesis seed oil is clear, rather than being golden in color, and offers the advantage of having an extended shelf-life without becoming rancid. However, in the practicc of the subject invcntion color is not of importance and oil stabilization can be achieved by adding a small amount of a soluble antioxidant, such as Vitamin E to the antifungal serum. In any casc, the Simmondsia chinesis seed oil can be refined by extracting it from unrefined material with an organic solvent, such as n-hcxane or cyclohexanc, and thcn fractionally distilling the extract to remove the organic solvent.

In cases where Vitamin E (a-tocopherol, 3 -tocophcrol, y-tocophcrol, and!or 6-tocophcrol) is utilized in the pharmaceutical serum it is typically present at a level which is within the range of about 0.01 weight percent to about 2 weight percent, based upon the total weight of the antifungal serum. In cases where Vitamin E is utilized in the pharmaceutical serum it is more typically added at a level which is within the range of 0.05 weight percent to about 1 weight percent, and is generally employed at a level which is within the range of 0.1 weight percent to 0.5 weight percent, based upon the total weight of the pharmaceutical serum.

A wide variety of pharmaceutical agents can be utilized in the pharmaceutical serums of this invention. For instance, the pharmaceutical agent can be selected from antifungal agents, hormones, growth factors, antimicrobials, antibacterials, antibiotics, non-steroidal anti-inflammatory agents, imniunodilators, anesthetics, plant extracts, vitamins, vitamin derivatives, corticosteroids, hair growth stimulants, and the like.

In one embodiment of this invention the pharmaceutical agent is an antifungal agent.

A wide variety of antifungal agents can be utilized in the antifungal serums of this invention.

For instance, the antifungal agent can be selected from azoles or imidazoles, including but not limited to, miconazole, econazole, terconazole, saperconazole, itraconazole, butaconazolc, clotrimazolc, tioconazolc, fluconazolc and ketoconazolc, vcriconazolc, fcnticonazole, scrtaconazole, posaconazolc, bifonazolc, oxiconazolc, sulconazolc, clubiol, vorconazolc, isoconazolc, flutrimazole, tioconazolc and their pharmaceutically acceptable salts and the like. The antifungal agent can also be an allylaminc or it can be selected from

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other chemical families, including but not limited to, ternafine, naftiflne, amorolfine, butenafine, ciclopirox, griseofulvin, undecyclenic acid, haloprogin, tolnaftate, nystatin, iodine, rilopirox, BAY 108888, purpuromycin and their pharmaceutically acceptable salts.

However, the preferred antifungal agents for utilization in conjunction with this invention include clioquinol, haloprogin, miconazole nitrate, poridonc-iodinc, tolnaftate, undecylenic acid, calcium undecylenate, cobalt undecylenate, zinc undecylenate, and clotrimazole.

Undecylenic acid is a highly preferred antifungal agent for utilization in the practice of this invention.

The alkyl lactate will typically be present in the antifungal serums ofthis invention at a level which is within thc range of about 5 weight percent to about 80 weight percent and will more typically be present at a level \vhich is within the range of about 10 weight percent to about 70 weight percent. The alkyl lactate will commonly be present in the antifungal serums of this invention at a level which is within the range of about 10 weight percent to about 60 \veight percent and will more commonly be present at a level which is within the range of about 15 weight percent to about 60 weight percent. In most cases, the alkyl lactate will typically be present in the antifungal serums of this invention at a level which is within the range of about IS weight percent to about 50 weight percent.

The Simmondsia chinesis seed oil will typically be present in the antifungal serums of this invention at a level which is within the range of f about 5 weight percent to about 80 percent and more typically be present at a level which is within the range of about 10 weight percent to about 70 percent. The Simmondsia chinesis seed oil will commonly be present in the antifungal serums of this invention at a level which is within the range of about 10 weight percent to about 60 percent and more typically will be present at a level which is within the range of about IS weight percent to about 50 percent. In most cases, the Simmondsia chinesis seed oil will be present in the antifungal serums of this invention at a level which is within the range of about IS weight percent to about 45 percent and in many cases will preferably be present at a level which is within the range of about 15 weight percent to about 40 percent.

The antifungal agent will typically be present at a level of about 0.25 weight percent to about 40 weight percent and will more typically be present at a level which is within the range of about 0.5 weight percent to about 35 weight percent. The antifungal agent will commonly be present at a level of about 0.75 weight percent to about 30 weight percent and will more commonly be present at a level which is within the range of about 1 weight percent to about 30 weight percent. However, the level of antifungal agent utilized is highly dcpcndant upon thc idcntity of thc antifungal agcnt employed in thc antifungal scrum. For instance, undecylenic acid, calcium undecylenate, cobalt undecylenate, zinc undecylenate will typically be utilized alone or in a mixturc at a level which is within thc rangc of about 5 wcight pcrccnt to about 30 weight pcrccnt. Undccylenie acid, calcium undecylenate, cobalt undecylenatc, zinc undccylcnate will more typically bc utilizcd alone or in a mixturc at a lcvel which is within thc rangc of about 10 weight pcrccnt to about 25 wcight perccnt.

Undccylcnic acid, calcium undccylcnatc, cobalt undccylenatc, zinc undccylcnatc will most typically bc utilizcd alonc or in a mixturc at a levcl which is within thc rangc of about 15 wcight pcrccnt to about 25 wcight pcrccnt. Undecylcnic acid, calcium undecylcnatc, cobalt undecylenatc, zinc undccylcnate will prcfcrably bc utilizcd alonc or in a mixturc at a levcl which is within the range of about 20 weight percent to about 25 weight percent.

In cases where halopmgin, tolnaftate, or clotrimazole are utilized as the antifungal agent in the antifungal serums of this invention they will typically be incorporated at a level which is within the range of about 0.25 weight percent to about 2 weight percent.

Haloprogin, tolnaftate, or clotrimazole will more typically be incorporated into the antifungal serums of this invention at a level which is within the range of about 0.5 weight percent to about I.5 weight percent and will preferably be included at a level of which is within the range of about 0.75 weight percent to about 1.25 weight percent. It is normally most preferred for haloprogin, tolnaftate, or clotrimazole to be included in the antifungal serums of this invention at a level of! weightpercent.

In cases where poridone-iodine is utilized as the antifungal agent in the antifungal serums of this invention it will typically be incorporated at a level which is within the range of about 4 wcight pcrccnt to about 20 wcight pcrccnt. Poridone-iodinc will more typically bc incorporated into thc antifungal serums of this invcntion at a level which is within thc rangc of about 6 weight perccnt to about 14 wcight pcrccnt and will prcfcrably bc included at a levcl of which is within thc rangc of about 8 weight pcrccnt to about 12 wcight pcrccnt.

It is normafly most preferred for poridone-iodine to be included in the antifungal serums of this invention at a level of 10 weight percent.

In cases where miconazole nitrate is utilized as the antifungal agent in the antifungal serums of this invention it will typically be incorporated at a level which is within the range of about 05 weight percent to about 8 weight percent. Miconazole nitrate \vill more typically be incorporated into the antifungal serums of this invention at a level which is within the range of about 1 weight percent to about 4 weight percent and will preferably be included at a level of which is within the range of about 1.5 weight percent to about 3 weight percent. It is normally most preferred for miconazole nitrate to be included in the antifungal serums of this invention at a level of 2 weight percent.

In cases where clioquinol is utilized as the antifungal agent in the antifungal serums of this invention it will typically be incorporated at a level which is within the range of about 1 weight percent to about 10 weight percent. Clioquinol will more typically be incorporated into the antifungal serums of this invention at a level which is within the range of about 2 weight percent to about 4 weight percent and will preferably be included at a level of which is within the range of about 2.5 weight percent to about 3.5 weight percent. It is normally most preferred for clioquinol to be included in the antifungal serums of this invention at a level of 3 weight percent.

In one embodiment of this invention the alkyl lactate is present in the antifungal serum of this invention at a level which is within the range of about 15 weight percent to about 40 weight percent, wherein the Simmondsia chinesis seed oil is present at a level of about 15 weight percent to about 40 percent, wherein the an antifungal agent is at least one member selected from the group consisting of undecylenic acid, calcium undecylenate, cobalt undecylenate, zinc undecylenate present, and wherein the antifungal agent is present at a level of about 20 weight percent to about 25 weight percent.

In another embodiment of this invention the alkyl lactate is present in the antifungal serum of this invention at a level which is within the range of about 15 weight percent to about 40 \veight percent, wherein the Simmondsia chincsis seed oil is present at a level of about 15 \vcight percent to about 40 percent, wherein the an antifungal agent is at least one mcmber selected from the group consisting of undecylenic acid, calcium undccylcnate, cobalt undecylenate, zinc undecylenate present, and wherein the antifungal agent is present at a level of about 20 weight percent to about 25 weight percent.

In a further embodiment of this invention the ailcyl lactate is present in the antifungal serum of this invention at a level which is within the range of about 15 weight percent to about 35 weight percent, wherein the Simmondsia chinesis seed oil is present at a level of about IS weight percent to about 35 percent, wherein the an antifungal agent is at least one member selected from the group consisting of undecylenic acid, calcium undccylcnate, cobalt undccylcnate, zinc undccylenatc prcscnt, and whcrcin thc antifungal agent is prescnt at a level of about 20 weight perccnt to about 25 wcight percent.

In a further embodiment of this invention the alkyl lactate is present in thc antifungal serum of this invention at a level which is within the range of about 15 weight pcrcent to about 30 weight percent, whercin thc Simmondsia chinesis seed oil is present at a level of about 15 wcight percent to about 30 percent, wherein thc an antifungal agcnt is at least one member selcctcd from thc group consisting of undecylenic acid, calcium undccylcnate, cobalt undecylenate, zinc undecylenate present, and wherein the antifungal agent is present at a level of about 20 weight percent to about 25 weight percent.

In still another embodiment of this invention the alkyl lactate is present in the antifungal serum of this invention at a level which is within the range of about 15 weight percent to about 25 weight percent, wherein the Simmondsia chinesis seed oil is present at a level of about IS weight percent to about 25 percent, wherein the an antifungal agent is at least one member selected from the group consisting of undecylenic acid, calcium undecylenate, cobalt undecylenate, zinc undecylenate present, and wherein the antifUngal agent is present at a level of about 20 weight percent to about 25 weight percent.

In another embodiment of this invention the alkyl lactate is present in the antifungal serum of this invention at a level which is within the range of about 20 weight percent to about 80 weight percent, the Simmondsia chinesis seed oil is present at a level of about 20 weight percent to about 80 percent, and the antifungal agent is selected from the group consisting ofhaloprogin, tolnaftatc, or clotrimazoleand is present at a level which is within the range of about 0.25 weight percent to about 2 weight percent. In such compositions it is typically preferred for the ailcyl lactate to be present in the antifungal serum at a level which is within the range of about 20 weight percent to about 80 weight pement, for the Simmondsia chinesis seed oil to be present at a level of about 20 weight percent to about 80 percent, and for the antifungal selected from the group consisting of haloprogin, tolnaflate, or clotrirnazoleand to be present at a level which is within the range of about 0.5 weight percent to about 1.5 wcight. In such compositions it is typically morc preferrcd for thc alkyl lactate to be present in the antifungal serum at a level which is within the range of about 20 weight percent to about 80 wcight perccnt, for the Simmondsia chinesis seed oil to bc prcsent at a level of about 20 wcight percent to about 80 pcrccnt, and for thc antifungal sclectcd from thc group consisting ofhaloprogin, tolnafiate, or clotrimazolcand to bc prcscnt at a lcvel which is within thc rangc of about 0.75 wcight percent to about 1.75 weight. In such compositions it is typically most prcfcrrcd for the ailcyl lactate to bc prescnt in thc antifungal serum at a level which is within thc range of about 20 weight percent to about 80 weight pcrccnt, for thc Simmondsia chincsis sccd oil to bc prcscnt at a level of about 20 weight pcrccnt to about 80 pcrcent, and for thc antifungal selected from thc group consisting of haloprogin, tolnaftate, or clotrimazoleand to be present at a level of about 1 weight percent. The antifungal agent use in such antifungal serums will typically consist solely of tolnaftate at a level of I weight percent.

The antifungal serum can also include a wide variety of other oils. These additional oils are typically vegetable oils, such as peppermint oil and/or tea tree oil. Peppermint oil can optionally be included at a level which is within the range of about 5 weight percent to about 45 weight percent and is typically included at a level which is within the range of about 5 weight percent to about 40 weight percent. Peppermint oil is commonly included at a level which is within the range of about 10 weight percent to about 35 weight percent and is more commonly included at a level which is within the range of about IS weight percent to about 30 weight percent. Peppermint oil is preferably included in the antifungal serums of this invention at a level which is within the range of about 15 weight percent to about 25 weight percent.

Tea tree oil can optionally be included at a level which is within the range of about 5 weight percent to about 45 weight percent and is typically included at a level which is within the range of about 5 weight percent to about 40 weight percent. Tea tree oil is commonly -20 -included at a level which is within the range of about 10 weight percent to about 35 weight percent and is more commonly included at a level which is within the range of about 15 weight percent to about 30 weight percent. Tea tree oill is preferably included in the antiftngal serums of this invention at a level which is within the range of about IS weight percent to about 25 weight pcrccnt.

In one embodiment of this invention the additional oil in the antifungal serum is a combination of peppcrmint oil and tca trcc oil, whcrcin the peppermint oil is present at a level which is within the range of about 5 weight percent to about 45 weight percent, and wherein the peppermint oil is present at a level which is within the range of about 5 \veight percent to about 45 weight percent. In another embodiment of this invention the additional oil is a combination of peppermint oil and tea tree oil, wherein the peppermint oil is present at a level which is within thc range of about 5 weight percent to about 40 weight percent, and wherein the peppermint oil is present at a level which is within the range of about 5 weight percent to about 40 weight percent.

In a further embodiment of this invention the additional oil is a combination of peppermint oil and tea tree oil, wherein the peppeimint oil is present at a level which is within the range of about 10 weight percent to about 35 weight percent, and wherein the peppermint oil is present at a level which is within the range of about 10 weight percent to about 35 weight percent. Instill another embodiment of this invention the additional oil is a combination of peppermint oil and tea tree oil, wherein the peppermint oil is present at a level which is within the range of about I 5 weight percent to about 30 weight percent, and wherein the peppermint oil is present at a level which is within the range of about 15 weight percent to about 30 weight percent. In a preferred embodiment of this invention the additional oil additional oil is a combination of peppermint oil and tea tree oil, wherein the peppermint oil is present at a level which is within the range of about 15 weight percent to about 25 weight percent, and wherein the peppermint oil is present at a level which is within thc range of about 15 weight percent to about 25 weight percent.

A highly preferred antifungal serum which utilizes undccylcnic acid as its antifungal agent is comprised of isoamyl lactate which is present at a level which is within the range of about 15 \vcight percent to about 30 weight percent, Simmondsia chinesis seed oil which is -2! -present at a level of about 15 weight percent to about 30 weight percent, undecylenic acid which is present at a level with is within the range of about 15 weight percent to about 30 weight percent, the peppermint oil which is present at a level which is within the range of about IS weight percent to about 30 weight percent, and tea tree oil which is present in the at a level which is within the range of about 15 weight percent to about 30 weight percent. in such formulations the the isoarnyl lactate will typically be present at a level which is within thc range of about 15 weight percent to about 25 weight percent, the Simmondsia chinesis seed oil will typically be present at a level of about 15 weight percent to about 25 weight percent, the undecylenic acid will typically be present at a level with is within the range of about 20 weight percent to about 30 weight percent, the peppermint oil will typically be present at a level which is within the range of about 15 weight percent to about 25 weight percent, and the tea tree oil will typically be present in the at a level which is within the range of about 15 weight percent to about 25 weight percent. In such formulations the isoamyl lactate will more typically be present at a level which is within the range of about 18 weight percent to about 22 weight percent, the Simmondsia chinesis seed oil will more typically be present at a level of about 18 weight percent to about 22 weight percent, the undecylenic acid will more typically be present at a level with is within the range of about 23 weight percent to about 27 weight percent, the peppermint oil will more typically be present at a level which is within the range of about 18 weight percent to about 22 weight percent, and the tea tree oil will more typically be present in the at a level which is within the range of about 18 weight percent to about 22 weight percent. In such formulations the isoamyl lactate will generally be present at a level which is within the range of about 18 weight percent to about 20 weight percent, the Simmondsia chinesis seed oil will generally be present at a level of about 18 weight percent to about 20 weight percent, the undecylenic acid will generally be present at a level with is within the range of about 24 weight percent to about 26 weight percent, the peppermint oil will generally be present at a level which is within the range of about 18 weight percent to about 20 weight percent, and thc tea tree oil will generally be present in the at a level which is within the range of about 18 weight percent to about 20 weight percent.

Another preferred antifungal serum which utilizes tolnaftate as its antifungal agent is -22 -comprised of isoamyl lactate which is present at a level which is within the range of about weight percent to about 40 weight percent, Simmondsia chinesis seed oil which is present at a level of about 15 weight percent to about 40 weight pernent, tolnaftate which is present at a level with is within the range of about 0.25 weight percent to about 2 weight percent, pcppcrmint oil which is prcscnt at a lcvcl which is within thc range of about 15 wcight percent to about 40 weight percent, and tea tree oil which is present in the at a level which is within thc rangc of about 15 weight pcrccnt to about 40 wcight percent. in such formulations thc isoamyl lactate is typically present at a level which is within thc rangc of about 15 weight pcrccnt to about 30 weight percent, thc Simmondsia chincsis sccd oil is typically present at a level of about 15 wcight pcrccnt to about 30 wcight percent, thc tolnaftate is typically present at a level with is within thc range of about 0.5 wcight pcrccnt to about 1.5 wcight percent, thc peppermint oil is typically prcscnt at a level which is within thc rangc of about 15 wcight pcrccnt to about 30 weight percent, and thc tca trcc oil is prcscnt is typically prcscnt thc at a level which is within thc rangc of about 15 wcight percent to about 30 weight percent. In such formulations the isoamyl lactate is more typically present at a level which is within the range of about 20 weight percent to about 35 weight percent, the Simmondsia chinesis seed oil is more typically present at a level of about 20 weight percent to about 35 weight percent, the tohaftate is more typically present at a level with is within the range of about 0.75 weight percent to about 1.25 weight pernent, the peppermint oil is more typically present at a level which is within the range of about 20 weight percent to about 35 weight percent, and the tea tree oil is more typically present in the at a level which is within the range of about 20 weight percent to about 35 weight percent. In such formulations the isoamyl lactate is normally present at a level which is within the range of about 20 weight percent to about 30 weight percent, the Simmondsia chinesis seed oil is normally present at a level of about 20 weight percent to about 30 weight percent, the tolnaftate is normally present at a level with is within the range of about 0.75 wcight pcrccnt to about 1.25 weight pcrccnt, thc pcppermint oil is normally prcscnt at a lcvcl which is within thc rangc of about 20 wcight pcrccnt to about 30 wcight pcrccnt, and thc tca trcc oil is normally prcscnt in thc at a lcvcl which is within thc rangc of about 20 wcight pcrccnt to about 30 weight pcrccnt. In such antifungal scrum formulations thc isoamyl -23 -lactate is generally present at a level which is within the range of about 22 weight percent to about 28 weight percent, the Simmondsia chinesis seed oil is generally present at a level of about 22 weight percent to about 28 weight percent, the tolnaftate is generally present at a level with is within the range of about 0.75 weight percent to about 1.25 weight percent, the peppcrmint oil is generally prescnt at a level which is within thc range of about 22 weight percent to about 28 weight percent, and the tea tree oil is generally present in the at a level which is within the range of about 22 \vcight percent to about 28 weight percent.

In another embodiment of this invention the pharmaceutical agent is earnosic acid which is a naturally occurring antioxidant. Carnosic acid can be included in the formulations of this invention to provide a serum which can be topically applied to skin to provide it with a higher level of protection against photo-induced and other types of oxidative attack. The carnosic acid will typically be included in the skin cream formulation at a level which is within thc range of 0.01 weight percent to 3 weight percent. It is normally preferred to include the carnosic acid at a level which is within the range of 0.05 weight percent to 1.5 weight percent with levels of 0.1 weight percent to 1 weight percent being most preferred. The carnosic acid is naturally found in Libiatae plants, such as rosemary, maijoram, and sage. United States Patent 5,859,293 and United States Patent 5,256,700 disclose techniques for extracting high purity carnosic acid from rosemary and sage. For example, United States Patent 5,256,700 discloses a process for obtaining carnosic acid comprising extracting a vegetable material selected from the group consisting of sage and rosemary with an apolar solvent to obtain an extract containing apolar compounds including carnosic acid, contacting the extract with an adsorbent material having an affinity for polar compounds for adsorbing the carnosic acid to separate the carnosic acid from the apolar compounds of the extract, desorbing the adsorbent material with a polar solvent to obtain the camosic acid in the solvent and then evaporating the polar solvent from the camosic acid to obtain a residue containing the carnosic acid.

Some methods for the preparation of carnosic acid by chemical synthesis have also been proposed in the literature by W. L. Meyer et al. [Tetrahedron Letters 1966, 4261; 1968, 2963; J. Org. Chem. 41, 1005 (1976)]. However, the syntheses involved arc long and complex and, for economic reasons, cannot be applied to an industrial process. In addition, -24 -these syntheses lead to racemic mixtures of carnosic acid precursors and not to the pure enantiomers. It should also be pointed out that these works stop at the preparation of carnosic acid precursors and omit to describe the final preparation step(s). Another method of obtaining camosic acid has been described in the literature by Brieskom and Domling [Arch. Pharm. 302, 641 (1969)], comprising thc catalytic rcduction of carnosol. Once again, the application of this process on a large scale is not be envisaged because carnosol is not readily availablc on a commercial basis. For thcsc reasons thc carnosic acid used in thc skin crcams formulations of this invention will normally be obtained by cxtraction from a Libiatac plant, such as rosemary or marjoram. Accordingly, rosemary or marjoram extract will typically bc uscd in thc practicc ofthis invcntion as thc sourcc of carnosic acid.

However, to reduce the possibility of allergic reactions to the skin cream formulation the skin cream formulation will preferably be free of rosemary, sage, maijoram and other Libiatae plants.

Carnosic acid will typically be incorporated into the pharmaceutical serums of this invention as the extract of a Libiatae plant, such as rosemary or maijoram. In most cases the extract of the Libiatae phmt will be included in the pharmaceutical serum at a level of about 0.5 weight percent to about 30 weight percent. The extract of the Libiatae plant will typically be included in the pharmaceutical serum at a level of about 1 weight percent to about 15 weight percent, and will more typically be included at a level of about 2 weight percent to about 10 weight percent. It is normally preferred to include the extract of the Libiatae plant in the pharmaceutical serum at a level of about 3 weight peitent to about 8 weight percent. Such a sink rejuvenation serum can optionally contain up to about 5 weight percent glycerin and up to about 5 weight percent propylene glycol. It is typically preferred for such compositions to contain from about 0.05 weight percent to about 3 weight percent glycerin and from about 001 weight percent to about 3 weight percent propylene glycol. It is typically more preferred for such compositions to contain from about 0. I weight percent to about 1 weight percent glycerin and from about 0.05 weight percent to about 0.5 weight percent propylene glycol.

In another embodiment of this invention idebenone is included in the pharmaceutical serums of this invention as an antioxidant. Idebenone will typically be present in such -25 -pharmaceutical serums at a level which is within the range of about 0.0! weight percent to about 5 weight percent. The idebenone will preferably be present in such pharmaceutical serums formulation at a level which is within the range of about 0.05 weight percent to about 3 weight percent and will more preferably be present at a level which is within the rangc of about 0.1 weight percent to about 1 weight perccnt.

Palmitoyl pentapeptide stimulates human fibroblasts to produce collagen and elastin which fight wrinkle formation and can reduce or climinate existing wrinkles. Howevcr, as with all active ingredients in antiwrinkle formulations palmitoyl pcntapcptidc needs to be delivcred deep into thc dermis of thc skin structure to attain a maximum level of effectiveness. In still anothcr embodiment of this invcntion pharmaceutical scrums can bc compounded with palmitoyl pcntapcptidc to facilitate its topical delivery dccp into thc dermis of human paticnts. In such an embodiment of this invcntion thc palmitoyl pcntapcptidc can accordingly bc included in the pharmaceutical serum at a level which is within thc rangc of about 0.05 weight pcrccnt to about 8 weight pcrccnt. In such pharmaceutical serums the palmitoyl pentapeptide will more typically be included at a level which is within the range of about 0.5 weight percent to about 6 weight percent, and will preferably be include at a level which is within the range of about I weight percent to about weight percent. The palmitoyl pentapeptide will more preferably be included in the pharmaceutical serums of this invention at a level which is within the range of 2 weight percent to 4 weight percent.

In a further embodiment of this invention a hair growth stimulant is included in the pharmaceutical serum of this invention as the pharmaceutical agent. In most cases the hair growth stimulant will be a antihypertensive vasodilator medication, such as minoxidil(6-(1-piperidinyl)-2,4-pyrimidinedia mine 3-oxide) which is included in the serum at a level which is within the range of about 0.5 weight percent to about 12 weight percent. The hair growth stimulant will more typically be included in the serum at a level which is within the range of about 1 weight percent to about 8 weight percent. The hair growth stimulant will most typically be included in the serum at a level which is within the range of about 2 weight percent to about 5 weight percent. Such hair growth serums can be topically applied to an arca of skin where hair growth is desired to facilitate such hair growth. In most cases the -26 -hair growth serum will be applied repeatedly to the area of skin over an extended period of time during which hair growth and hair maintenance in the area is desired. In most cases the hair growth serum will be applied at least once a day and can optionally be multiple times each day, such as twice a day. For instance, the hair growth serum can be applied every morning and in the evening during the treatment period which can cxtend over many years.

In another embodiment of this invention a vitamin A derivative selected from the group consisting of retinol and retinoic acid is included in a skin rejuvenation serum.

Retinol based skin rejuvenation serums will typically contain retinol a level which is within thc range of about 0.1 weight percent to about 15 weight percent. Such serums will more typically contain from about 0.5 weight percent to about 12 weight percent retinol and will more typically contain from 1 weight percent to 10 weight percent retinol. It is preferred for such skin rejuvenation serums to contain from about 3 weight percent to about 8 weight percent retinol. On the other hand, retinoic acid based skin rejuvenation serums will typically contain from about 0.005 weight percent to about 0.5 weight percent retinoic acid.

Such skin rejuvenation serums will more typically contain from about 0.01 weight percent to about 0.4 weight percent retinoic acid and will preferably contain from about 0.02 weight percent to about 0.3 weight percent retinoic acid. Such skin rejuvenation serums will more preferably contain from about 0.03 weight percent to about 0.2 weight percent retinoic acid and will most preferably contain from about 0.04 weight percent to about 0.1 weight percent retinoic acid.

In a further embodiment of this invention an antimicrobial agent is included in the pharmaceutical serum of this invention. Some representative examples of antimicrobial agents that can be use include 2,4,4trichloro2?hydroxydiphenyl ether (or triclosan), 344' trichlorobanilide, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, hexaniidine isethionate, metronidazole and its salts, miconazole and its salts, itraconazole, terconazole, econazole, ketoconazole, saperconazole, fluconazole, clotrimazole, butoconazole, oxiconazole, sulfaconazole, sulconazole, terbinafinc, ciclopirox, ciclopiroxolaminc, undccylcnic acid and its salts, bcnzoyl peroxide, 3-hydroxybcnzoic acid, 4-hydroxybcnzoic acid, phytic acid, N-acetyl-L-cystcinc acid, lipoic acid, azelaic acid and its salts, arachidonic acid, resorcinol, 2,4,4-trichloro-2-hydroxydiphcnyl ether, 3,4,4-trichlorocarbanilidc, -27 -octopirox, octoxyglycerine, octanoylglycine, caprylyl glycol, IO-hydroxy-2-decanoic acid, dichiorophenyl imidazole dioxolane and its derivatives, described in patent WO 93/18743, famesol and phytosphingosines, and mixtures thereof The preferred antibacterial agents are triclosan, phenoxyethanol, octoxyglycerine, octanoylglycine, I O-hydroxy-2-decanoic acid, capiylyl glycol, farncsol and azclaic acid. Such antimicrobial agcnts will typically bc included at a level which is within the range ofO. I weight percent to 20 weight percent and will more typically bc included at a lcvcl which is within thc range of prcfcrably from 0.2 wcight percent to 10 wcight percent rclativc to the total wcight of thc pharmaceutical serum.

In still another cmbodimcnt of this invention thc pharmaccutical serum can include an agcnt for stimulating the synthcsis of dcrmal or cpidcrmal macromolecuics and!or for prcventing thcir dcgradation as thc pharmaccutical agcnt. Among thc activc agcnts for stimulating dcrmal macromolcculcs or for prcvcnting thcir dcgradation, mcntion may bc made of thosc that act: cither on collagen synthesis, such as cxtracts of Ccntclla asiatica; asiaticosidcs and dcrivatives; ascorbic acid or vitamin C and its dcrivativcs; synthctic peptides such as lamin, biopeptide CL or the palmitoyloligopeptide sold by the company Sederma; peptides extracted from plants, such as the soybean hydrolysate sold by the company Coletica under the trade name Phytokine®; and plant hormones such as auxins and lignans; or on elastin synthesis, such as the extract of Sacchammyces cerivisiae sold by the company LSN under the trade name Cytovitin®; and the extract ofthe alga Macrocystis pyrifera sold by the company Secrna under the trade name Kelpadelie®; or on glycosaminoglycan synthesis, such as the product of fermentation of milk with Lactobacillus vulgaris, sold by the company Brooks under the trade name Biomin yogourth®; the extract of the brown alga Padina pavonica sold by the company Alban Muller under the trade name HSP3; and the extract of Saccharomyces cerevisiae available especially from the company Silab under the trade name FirmaliftR) or from the company LSN under the trade name Cytovitin®; or on fibronectin synthesis, such as the extract of the zooplankton Salina sold by the company Scporga undcr thc tradc namc GP4G®; thc ycast cxtract availablc cspecially from thc company Alban Mullcr undcr thc tradc namc Driclinc®; and thc palmitoyl pcntapcptidc sold by thc company Scdcrma undcr thc trade namc Matrixil; or on the inhibition of mctalloprotcascs (MMPs), such as, morc particularly, MMP 1,2, 3 or 9. -28 -

Mention may be made of: retinoids and derivatives, oligopeptides and lipopeptides, lipoamino acids, the malt extract sold by the company Coletica under the trade name Collalifi®; extracts of blueberry or of rosemary; lycopene; isoflavones, their derivatives or plant extracts containing them, in particular extracts of soybean (sold, for example, by the company Ichimaru Pharcos under the trade name Flavosterone SB®), of red clover, of flax, of kakkon, or of sage; or on the inhibition of serine proteases such as leukocyte elastase or cathepsin G. Mention may be made of: the peptide extract of Leguminosa seeds (Pisum sativum) sold by the company LSN under the trade name Parelastyl®; heparinoids; and pseudodipeptides such as 2-[acetyl-(3-trifluoromethylphenyl)amino] -3-methylbutynylamino) acetic acid.

Among the active agents that stimulate epidermal macromolecules, such as fihlagrin and keratins, mention may be made especially of the extract of lupin sold by the company Silab under the trade name Structurine®; the extract of beech Fagus sylvatica buds sold by the company Gattefosse under the trade name Gatuline®; and the extract of the zooplankton Sauna sold by the company Seporga under the trade name GP4G®.

The pharmaceutical serum of this invention can optionally contain an agent for stimulating the proliferation of fibroblasts or keratinoeytes and/or keratinoeyte differentiation as the pharmaceutical agent. The agents for stimulating the proliferation of fibroblasts that may be used in the composition according to the invention may be chosen, for example, from plant proteins orpolypeptides, extracts, especially of soybean (for example an extract of soybean sold by the company LSN under the name Elesemyl SH-VEG 8 or sold by the company Silab under the trade name Raffermine®); and plant hormones such as giberrellins and cytokinins.

The agents for stimulating the proliferation of keratinoeytes that may be used in the composition according to the invention especially comprise retinoids, such as retinol and its esters, including retinyl palmitate; phloroglueinol; extracts of nut cakes sold by the company Gattefosse; and extracts of Solanum tuberosum sold by the company Sederma.

The agents for stimulating keratinoeyte differentiation comprise, for example, minerals such as calcium; the extract of lupin sold by the company Silab under the trade name Photopreventine®; sodium beta-sitosteryl sulphate sold by the company Seporga -29 -under the trade name Phytocohesine®; and the extract of corn sold by the company Solabia under the trade name Phytovityl®; and lignans such as secoisolariciresinol. The composition according to the invention comprising these compounds is preferably intended to be used for preventing or treating signs ofageing of the skin.

The pharmaceutical serum of this invention can optionally further contain a dcrmo-decontracting agent as the pharmaceutical agent. The dermo-decontracting agents that may be used in the pharmaceutical serum ofthis invention includc alvcrine and its salts, manganese gluconate, Diazepam, thc hexapeptide argireline R sold by thc company Lipotec, certain carbonylated secondaiy and tertiary amincs, adcnosine, and also sapogenins and the natural extracts, in particular of Wild Yam, containing them.

The pharmaceutical serum of this invention can optionally further contain agents for acting on the capillary circulation as their pharmaceutical agent. The active agents acting on thc capillary circulation (vasoprotective or vasodilating agents) may be chosen from flavonoids, ruscogenins, eseulosides, escin extracted from common horse chestnut, nicotinates, heperidine methyl chalcone, essential oils of lavender or of rosemary, and extracts of Ammi visnaga. The amount of these active agents may vary within a wide range.

In general, these active agents are present in a concentration ranging from 0.01% to 15% and preferably from 0.05% to 10% by weight relative to the total weight ofthe pharmaceutical serum.

The pharmaceutical serum of this invention can optionally further contain agents acting on the energy metabolism of cells as their pharmaceutical serum. The active agents concemed are those acting on the energy metabolism of the skin, for instance, and in a non-limiting manner, ATP synthesis, and also those involved in the respiratory chain of the cell or in the energy reserves. Mention may be made of coenzyme Q 10 ubiquinone), cytochrome C, creatine or phosphocreatine The alkyl lactate will typically be present in the pharmaceutical serums of this invention at a level which is within the range of about 5 weight percent to about 80 weight percent and will more typically be present at a level which is within the range of about 10 weight percent to about 70 weight percent. The ailcyl lactate will commonly bc present in thc pharmaceutical serum of this invention at a level which is within the range of about 10 weight percent to about 60 weight percent and wiH more commonly be present at a level which is within the range of about 15 weight percent to about 60 weight percent. Inmost cases, the alkyl lactate will typically be present in the pharmaceutical serum ofthis invention at a level which is within the range of about IS weight percent to about 50 weight percent.

Thc Simmondsia chincsis sccd oil will typically bc prcscnt in thc pharmaccutical serum of this invention at a level which is within the range off about 5 weight percent to about 80 pcrccnt and morc typically bc prcscnt at a lcvcl which is within thc rangc of about wcight pcrccnt to about 70 pcrccnt. Thc Simmondsia chincsis sccd oil will commonly bc prcscnt in thc pharmaccutical scrum ofthis invcntion at a lcvcl which is within thc rangc of about 10 weight percent to about 60 percent and morc typically will bc present at a level which is within thc rangc of about 15 weight percent to about 50 percent. In most cases, thc Simmondsia chincsis sccd oil will bc prcscnt in thc pharmaccutical scrum ofthis invention at a lcvcl which is within thc rangc of about 15 wcight pcrccnt to about 45 pcrccnt and in many cascs will preferably bc prcscnt at a lcvcl which is within thc rangc of about 15 wcight percent to about 40 percent.

The level of pharmaceutical agent which is present in the pharmaceutical serums of this invention will very greatly with the nature of the phamiaceutical agent and the therapeutic result which is desired. However, the pharmaceutical agent will typically be present in the pharmaceutical serums of this invention at a level which is within the range of 0.00! weight percent to 40 weight percent and will more typically be present at a level which is within the range of about 0.0! weight percent to 35 weight percent. The pharmaceutical agent will commonly be present in the pharmaceutical serums of this invention at a level which is within the range of 0.02 weight percent to 30 weight percent and can be present at a level which is within the range of about 0.025 weight percent to 25 weight percent. For instance, the phannaceutical agent can be present in the pharmaceutical serums of this invention at a level which is within the range of 0.05 weight percent to 25 wcight pcrccnt. In some cascs thc pharmaceutical agcnt will bc prcscnt at a relatively low level which is within thc rangc of 0.01 wcight percent to 0.5 weight percent or which is within thc rangc of 0.02 weight pcrccnt to 0.3 wcight percent. In othcr cascs thc pharmaccutical agcnt will bc prcscnt at a relatively lcvcl which is within thc range of 0.1 -3! -weight percent to 25 weight percent or which is within the range of 5 weight percent to 25 weight percent or which is within the range of 10 weight percent to 25 weight percent or which is within the range of 15 weight percent to 25 weight percent.

The pharmaceutical serum of this invention can also include a wide variety of other oils. These additional oils arc typically vegetable oils (oils of plant origin), mineral oils (liquid petroleum jelly), oils of animal origin (such as lanolin), synthetic oils (perhydrosqualene), or a silicone oils (cyclomethicone). The vegetable oils that can be included in the pharmaceutical serum of this invention include avocado oil, soybean oil, coconut oil, shea butter, almond oil, eucalyptus essential oil, olive oil, hazelnut oil, walnut oil, peanut oil, corn oil, caster oil, soy oil, eanola oil, rapeseed oil, cottonseed oil, palm oil, sesame oil, sunflower oil, safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil, hempseed oil, flaxseed oil, rape seed oil, evening primrose oil, rosehip oil, and melaleuca oil. Some represcntative examples of animal based oils that can optionally be utilized include lanolin, various fish oils, such as herring oil, cod-liver oil, and salmon oil.

Typically, the pharmaceutical serum ofthis invention will be void of these additional oils since they are not believed to serve any beneficial purpose and dilute the levels of the more desirable components of the serum, such as the Simmondsia chinesis seed oil and the alkyl lactate which facilitate the delivery of the pharmaceutical agent into the skin. Accordingly, in cases where such oisl are included in the pharmaceutical serum their total level will normally be limited to be within the range of 0 weight percent to about 25 weight percent and will more typically be limited to be within the range of 0 weight percent to 10 weight percent, based upon the total weight of the pharmaceutical serum. In cases where such additional oils are included they will normally be present in a total amount which is within the range of about I weight percent to about 5 weight percent.

Fatty alcohols (cetyl alcohol), fatty acids, petrolatum, and waxes (carnauba wax or ozokerite) can also optionally be included in the pharmaceutical serum of this invention.

Petrolatum or mineral oil components, which when selected will generally be LiSP or NF grade. The petrolatum may be white or yellow. The viscosity or consistency grade of petrolatum is not narrowly critical. Petrolatum can be partially replaced with mixtures of hydrocarbon materials, which can be formulated to resemble petrolatum in appearance and -32 -consistency. For example, mixtures ofpetrolatum or mineral oil with different waxes and the like may be combined. Preferred waxes include bayberry wax, candelilla wax, ceresin, jojoba butter, lanolin wax, montan wax, ozokerite, polyglyceryl-3-beeswax, polyglyceryl-6-pentastearate, microcrystalline wax, paraffin wax, isoparaffin, vaseline solid paraffin, squalene, oligomer olefins, beeswax, synthetic candelilla wax, synthetic carnauba, synthetic beeswax and the like may be blended together. Typically, the pharmaceutical serum of this invention will be void of petrolatum and waxes since they are not believed to serve any beneficial purpose and dilute the levels of more desirable ingredients. Accordingly, in cases where petrolatum and/or waxes are included in the pharmaceutical serum their total level will normally be limited to be within the range of 0 weight percent to about 25 weight percent and will more typically be limited to be within the range of 0 weight percent to 10 weight percent, based upon the total weight of the pharmaceutical serum. In cases where petrolatum and/or such waxes are included they will normally be present in a total amount which is within the range of about 1 weight percent to about 5 weight percent.

The pharmaceutical serum of this invention can be made by simply mixing the desired constituents under conditions that are adequate to attain an essentially homogeneous mixture at a temperature which is typically within the range of about 10°C to about 100°C.

In most cases this can be accomplished by mixing the constituents at room temperature (18°C to 23°C). However, in some cases it is desirable to heat the components being mixed to a slightly elevated temperature which is within the range of about 30°C to 60°C to facilitate mixing.

This invention is illustrated by the following examples that are merely for the purpose of illustration and are not to be regarded as limiting the scope ofthe invention or the manner in which it can be practiced. Unless specifically indicated otherwise, parts and percentages are given by weight.

Example 1

In this experiment an antifungal scram of this invention was prepared by adding 25 mlofjojoba oil (filtered and unrefined), 25 ml of peppermint oil, 25 ml of tea tree oil, 25 ml of isoamyl lactate, and 25 nil of undccylcnic acid to a 250 ml beaker. Then, the mixture of -33 -liquids were well mixed with a stirring rod to make the antifungal serum.

The antifungal serum was subsequently used to treat the toenail of a 59 year old male who was suffering from onychomycosis. The onychomycosis was the result of trauma caused by stubbing the big toe of the patient on a bed post. In this case, the onychomycosis was black in appearance and was located under the toenail. Thc antifungal serum was brushed onto the infected toe of the patient every morning, in the early afternoon, and in the evening every day.

After about one week of treatment the black color of thc fungus lightened and the toenail returned to a relatively normal appearancc. Thc application of thc antifungal serum was continued in thc morning and in the evening for about 6 months to allow the infected toenail to completely grow out leaving only a normal nail structure. There was no reoccurrence of the onyehoniyeosis after another 6 months. In other words, the patient remained free of fungus for 6 months after discontinuing treatment with the antifungal scrum.

Example 2

An antifungal serum was made as described in Example I and was subsequently used to treat a patient with Down's Syndrome who had been suffering from onychomycosis for many years. All ten of toes of this 30 year old male subject were severely infected with onychomycosis. In any case, the antifungal serum was applied to the toenails of the patient at least twice every day. After about 6 months of treatment the onychoniycosis was completely eliminated from all ofthe toes of this patient. However, onychomycosis did reoccur and treathent was resumed on the infected toes. The subsequent treatment again eliminated the onychomycosis after several months of further treatment.

Example 3

An antifungal serum was made as described in Example 1 and was subsequently used to treat a patient with diabetes mellitus who had been suffering from onychomycosis for many years. All ten of toes of this 65 year old male subjcct were severely infected with onychomycosis. In any case, the antifungal serum was applied to the toenails of the patient at least twice every day. After about 6 months of treatment the onychomycosis was completely eliminated from all ofthe toes of this patient. There was no reoccurrence ofthe onychomycosis after another 2 months. In other words, the patient remained free of fungus for 2 months after discontinuing treatment with the antifungal serum.

Example 4

An antifungal serum was made as described in Example 1 and was subsequently used to treat a 75 year old female patient that was otherwise healthy who had been suffering from onychomycosis for about 6 months. She had previously treated the onychomycosis which several over the counter products without success. Most of her toes were severely infected with the onychomycosis. In any case, the antifungal serum was applied to the toenails of the patient at least twice every day. After about 6 months of treatment the onychomycosis was completely eliminated from all of the toes of this patient. There was no reoccurrence of the onychoniycosis after another 6 months. In other words, the patient remained free of fungus for 6 months after discontinuing treatment with the antifungal serum.

Example S

An antifungal serum was made as described in Example 1 and was subsequently used to treat aSS year old female patient that was otherwise healthy who had been suffering from onychomycosis for over 2 years. She had previously treated the onychomycosis which several over the counter products without success. Most of her toes were severely infected with the onychomycosis. In any case, the antifungal serum was applied to the toenails of the patient at least twice every day. After about 6 months of treatment the onychomycosis was completely eliminated from all of the toes of this patient. There was no reoccurrence of the onychomycosis after another 6 months. In other words, the patient remained free of fungus for 6 months after discontinuing treatment with the antifungal serum. -35 -

Example 6

In this experiment a skin rejuvenation serum of this invention was prepared by adding 90 ml ofjojoba oil (filtered and unrefined), 5 nil of rosemary extract, and 5 ml of isoamyl lactate to a 150 ml beaker. Then, the mixture of liquids was then well mixed with a stirring rod to make a skin rejuvenation serum.

Example 7

In this experiment a skin rejuvenation serum of this invention was prepared by adding 88 ml ofjojoba oil (filtered and unrefined), S ml of rosemary extract, 5 ml of isoamyl lactate, 1 ml of glycerin, and 1 ml of propylene glyeol to a 150 ml beaker. Then, the mixture of liquids was then well mixed with a stirring rod to make a skin rejuvenation serum.

Example 8

In this experiment a skin rejuvenation serum of this invention was prepared by adding about 50 ml ofjojoba oil (filtered and unrefined), S ml of rosemary extract, and SO ml ofisoaniyl lactate to a ISO nil beaker. Then, the mixture of liquids was then well mixed with a stirring rod to make a skin rejuvenation serum.

While certain representative embodiments and details have been shown for the purpose of illustrating the subject invention, it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the subject invention. -36 -

Claims (11)

1. WHAT IS CLAiMED IS: 1. A pharmaceutical serum which is comprised of(1) an alkyl lactate, wherein the alkyl group in the alkyl lactate contains from 2 to about 12 carbon atoms, (2) Simmondsia chincsis seed oil, and (3) a pharmaceutical agent.
2. 2. Thc pharmaceutical scrum as specified in claim 1 whcrcin the ailcyl lactate is isoamyl lactate.
3. 3. The pharmaceutical serum as specified in claim 1 or claim 2 wherein the Simmondsia chinesis seed oil is golden Simmondsia ehinesis seed oil.
4. 4. Thc pharmaceutical serum as specified in claim 1 or claim 2 wherein the Simmondsia chincsis seed oil is filtered.
5. 5. The pharmaceutical serum as specified in any of claim 1 or claim 2 wherein the Simmondsia chinesis seed oil is refined.
6. 6. The pharmaceutical serum as specified in any of the preceding claims wherein the alkyl lactate is present at a level which is withm the range of about 5 weight percent to about 90 weight percent, wherein the Simniondsia chinesis seed oil is present at a level of about S weight percent to about 90 percent, and wherein the pharmaceutical agent is present at a level of about 0.01 weight percent to about 40 weight percent.
7. 7. The pharmaceutical serum as specified in any of the preceding claims wherein the pharmaceutical agent is selected from the group consisting of antilngal agents, hormones, growth factors, antimicrobials, antibacterials, antibiotics, non-steroidal anti-inflammatory agents, immunodilators, anesthetics, plant extracts,vitanins, cortieosteroids, and hair growth stimulants. -37 -
8. 8. The pharmaceutical set-urn as specified in cairn 7 wherein the pharmaceutical agent is minoxidil.
9. 9. The pharmaceutical serurn as specified in dairn 7 wherein the pharmaceutical agent is an antihypertcnsivc vasodilator.
10. 10. The pharmaceutical serum as specified in any of claims 1-6 wherein the pharmaceutical agent is a vitamin A derivative selected from the group consisting of rctinol and rctinoic acid.
11. 11. The pharmaceutical serum as specified in any of claims 1-6 wherein the pharmaceutical agent is a growth factor.13. The pharmaceutical serum as specified in any of claims 1-6 wherein the pharmaceutical agent is an antifungal agent.14. The pharmaceutical semrn as specified in claim 13 wherein the antifungal agent is selected from the group consisting of clioquinol, haloprogin, miconazole nitrate, poridone-iodine, tolnaftate, undecylenic acid, calcium undecylenate, cobalt undecylenate, zinc undecyknate, and dotrirnazole.15. The pharmaceutical serum as specified in any of claim 13 wherein the antifungal agent is tolnaftate.16. The pharmaceutical serum as specified in any of claim 13 wherein the antifungal agent is undecylenic acid.17. The pharmaceutical serum as specified in any of claim 14, 15, or 16 wherein thc alkyl lactate is present at a level which is within the range of about 15 weight percent to about 50 weight percent, wherein the Simmondsia chincsis seed oil is present at a level of -38 -about 15 weight percent to about 50 percent, and wherein the an antifungal agent is pmsent at a level of about 1 weight percent to about 30 weight percent.18. The pharmaceutical serum as specified in any of claim 13 wherein the alkyl lactatc is prcscnt at a lcvcl which is within thc rangc of about 15 weight pcrccnt to about 40 weight percent, wherein the Simmondsia chinesis seed oil is present at a level of about 15 wcight perccnt to about 40 percent, whcrcin thc an antiffingal agcnt is at least onc mcmbcr sclcctcd from thc group consisting ofundecylenic acid, calcium undccylcnatc, cobalt undccylcnatc, zinc undccylenatc prcscnt, and whcrcin the antifungal agcnt is prcscnt at a lcvcl of about 20 wcight pcrccnt to about 25 weight pcrccnt.19. Thc pharmaceutical scrum as spccificd in any of claim 18 whcrcin the pharmaccutical serum is further cornpriscd of pcppcrrnint oil.20. The pharmaceutical serum as specified in claim 19 wherein the pharmaceutical serum is further comprised of tea tree oil.21. A method for treating a human fingernail or toenail which is infected with onychomycosis which comprised applying the pharmaceutical serum specified in any of claims 13 through 20 to the infectednail.22. A method for treating hair loss which comprised topically applying the pharmaceutical serum as specified in claim 8 or 9 to an area of skin where hair growth is desired.