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WO1993023061A1 - Usilisations therapeutiques de substances vegetales acres et des composes derives - Google Patents

Usilisations therapeutiques de substances vegetales acres et des composes derives Download PDF

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Publication number
WO1993023061A1
WO1993023061A1 PCT/US1993/004763 US9304763W WO9323061A1 WO 1993023061 A1 WO1993023061 A1 WO 1993023061A1 US 9304763 W US9304763 W US 9304763W WO 9323061 A1 WO9323061 A1 WO 9323061A1
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analog
diseases
applying
compound
amount sufficient
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PCT/US1993/004763
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WO1993023061B1 (fr
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Jeff J. Staggs
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Staggs Jeff J
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Priority to GB9423318A priority Critical patent/GB2286120B/en
Priority to US08/338,489 priority patent/US6063381A/en
Priority to DE4392300T priority patent/DE4392300T1/de
Publication of WO1993023061A1 publication Critical patent/WO1993023061A1/fr
Publication of WO1993023061B1 publication Critical patent/WO1993023061B1/fr
Priority to US09/571,644 priority patent/US6593371B1/en
Priority to US10/620,794 priority patent/US20050058729A1/en

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    • C—CHEMISTRY; METALLURGY
    • C06—EXPLOSIVES; MATCHES
    • C06D—MEANS FOR GENERATING SMOKE OR MIST; GAS-ATTACK COMPOSITIONS; GENERATION OF GAS FOR BLASTING OR PROPULSION (CHEMICAL PART)
    • C06D7/00—Compositions for gas-attacks
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/16—Oxygen or sulfur directly attached to an aromatic ring system with two or more oxygen or sulfur atoms directly attached to the same aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
    • A01N43/26—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings
    • A01N43/28—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3
    • A01N43/30—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3 with two oxygen atoms in positions 1,3, condensed with a carbocyclic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
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    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08—Magnoliopsida [dicotyledons]
    • A01N65/18—Euphorbiaceae [Spurge family], e.g. ricinus [castorbean]
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08—Magnoliopsida [dicotyledons]
    • A01N65/38—Solanaceae [Potato family], e.g. nightshade, tomato, tobacco or chilli pepper
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/40—Liliopsida [monocotyledons]
    • A01N65/48—Zingiberaceae [Ginger family], e.g. ginger or galangal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/008—Preparations for oily hair
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to a new class of general antiinfective compounds obtainable from plant species of the pepper, and ginger families, and chemically related species that are also useful in the treatment of tissue injury, and skin disorders.
  • Pathogenic bacteria, viruses, rickettsia, and fungi may cause disease in their host organism whether plant, animal, or man.
  • mycoses Fungal diseases of man and animals, often referred to as mycoses, may be classified into two broad categories. Deep tissue, or systemic mycoses involves the wide dissemination of pathogenic fungi growing in internal organs, and tissue, and superficial mycoses, which generally represent different types of pathogenic fungi than' those that infect the skin, hair, nails and mucosa.
  • Deep tissue mycoses including aspergillosis, actino ycosis, blasto ycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, nocardiosis, paracoccidioidomycosis, entomophthoromycosis and occasionally Candida, may infect the lungs, brain, bones, spinal fluid, liver, heart, kidneys, and other internal organs, as well as the skin. Depending on severity, deep tissue mycoses may cause .illness that ranges from asymptomatic to life threatening.
  • Superficial mycoses also called der atophytosis, describe disorders such as ringworm, athlete's foot, favus and Candida, which infect the skin, hair, nails and mucosal linings. There are perhaps three dozen or so known species of pathogenic fungi, and yeasts responsible for causing these diseases.
  • Tinea is another term used to describe ringworm. It is usually followed by another term which describes the particular location of the infection. Hence, athletes foot is often referred to as “tinea pedis”. Scalp ringworm is also known as “tinea capitis”; body ringworm as “tinea corporis”, jock itch as “tinea cruris” etc. Though not considered to be. life threatening, as some deep tissues mycoses can be, superficial mycoses assuredly take a fair toll of man and animals in misery, inconvenience, and expense.
  • a young woman who develops bald patches on her scalp due to ringworm may feel that she has a serious illness. It is also likely that she may feel the same about a ringworm infection of the fingernails, where the nails assume a serious, unsightly appearance as a result of thickening, brittleness and discoloration typical of the disease. Add to this a year and a half of systemic treatment to see results, and she may feel that she indeed has a very serious illness.
  • Antibiotic drugs such as penicillin, tetracycline, and sulfa ect., though often effective in the treatment of bacterial infections, are useless against infections caused by viruses, rickettsia, and fungi. Fungal disorders, for example require treatment with a separate group of antimicrobial drugs, known as antifungals, or antimycotics.
  • Antimycotic drugs (fig. 14 - 16) were first introduced in the 1950's with nystatin (1954), amphotericin B (1958), and griseofulvin (1959). These drugs were originally administered systemically. Tolnaftate (fig. 17) was introduced in 1965 as the first effective topical antifungal treatment. Since the 1970's, a number of "azole” derivative antifungals such as clotimazole (fig. 20), miconazole (fig. 21), econazole (fig. 22), ketoconazole, and others have made their appearance as antimycotics for both systemic, and topical administration. The more current trend has been toward the developement of a "triazole” (fig. 23) class of antifungals, including such derivatives as fluconazole (fig. 24), terconazole (fig. 25), and itraconazole ect..
  • Prior art treatments for superficial mycoses require repeated application before improvement can be seen in the patient.
  • Currently available over the counter treatments containing clotrimazole, miconazole, tolnaftate, or undecylenic acid, recommend up to sixty applications of the product in order to provide full benefit. More treatments are often required.
  • Ringworm being highly contagious, can spread through a herd within a few short weeks, not allowing enough time for treatment and recovery in the weeks prior to going to market, even if they are treated.
  • treating food animals for ringworm is an unreasonable notion.
  • the cost involved in applying a medicine, perhaps fifty times, to a single head of livestock could never be justified. For this reason, treatment is withheld, to the disadvantage of both the rancher and the animal, which in addition to suffering discomfort, spreads the disease to other animals, perpetuating the cycle further.
  • no viable solution is offered by pharmaceutical manufacturers which would otherwise enjoy a new, very large potential market.
  • Systemic antifungal drugs are also used to treat superficial mycoses, in addition to the deep tissue diseases. Drugs like amphotericin B, clotrimazole, enconazole, griseofluvin, ketoconazole, miconazole, and nystatin, are administered internally, usually orally, or by injection. Like the topical antifungals described earlier, most of the systemics treatments require multiple doses in order to be effective. Systemic treatments are the most costly of all, requiring the supervision of a physician. They are most dangerous to the patient, with undesirable side effects that can further endanger the health of the patient. The risk of damage to internal organs, and adverse reactions to other medications, are factors that must be carefully weighed by physicians administering systemic antifungals. With this, other less severe, yet unpleasant side effects, include nausea, vomiting, headache, dizziness, fever, diarrhea, and many other adverse effects that contribute to the misery and ill health of the patient.
  • Amphotericin B (fig. 14), given by injection in the treatment of systemic fungal infection, carries with it the risk of liver and kidney damage, and can also result in blood disorders. It interacts negatively with many cardiac medications, and diuretics, as well as other antibiotics.
  • Griseofulvin (fig. 16), usually taken orally, for fungal infections of the skin, hair, and nails, has a risk of liver damage. Reduced bone marrow function, with lowered white cell levels is another possible adverse effect of treatment. Drug interactions with anticoagulants, and barbiturates reduce effectiveness, and the risk to pregnancy often forbids treatment.
  • Ketoconazole taken orally for systemic fungal infections, also carries the risk of liver damage as a result of treatment.
  • the effectiveness of ketoconazole is diminished by interaction with various antacids, and other gastric medications.
  • Ketoconazole increases the potency of other drugs, and is reduced in potency by some antibiotics.
  • Miconazole (fig. 21), taken by injection for fungal infection of the lungs, brain, kidney, and lymph nodes, can alter blood chemistry resulting in anemia. Miconazole also interacts negatively with medications for diabetes, epilepsy and anticoagulants. The effectiveness of amphotericin B is reduced by miconazole.
  • Nystatin (fig. 15), taken orally for Candida disorders, is of little use in the treatment of systemic fungal infections. Though having far fewer adverse side effects than the other antifungal drugs, it is ineffective against most fungal infections except Candida, and aspergillus, making it of limited usage.
  • Topical treatment of superficial mycoses is much safer than internal treatments.
  • the prior art has failed to produce topical antifungal medications effective enough to deal with more serious infections. This necessitates the use of systemic treatments, which are more dangerous, costly, time consuming, and associated with many other unpleasant illnesses to treat even superficial mycoses.
  • Deep tissue mycoses find their greatest opportunity in immunocomprimised patients. These include cancer, organ transplant patients, and others on immunosuppressant medication, and particularly with patients suffering from immune disorders such as acquired immune deficiency syndrome, otherwise known as AIDS. These patients, who are very ill indeed, are highly susceptible to infection from these diseases, as their natural defenses against the pathogenic microbes is greatly reduced. The adverse effects of treatment with currently available prior art systemic antifungals, are devastating to immunocomprimised patients, to the point of being themselves life threatening to the patient. To those patients in greatest need of treatment for deep tissue mycoses, the medication is most dangerous to administer.
  • my invention includes a method for treating fungal infections, otherwise known as mycoses, in which cure is complete with as few as one single application of my medication. Rather than making scores of applications, usually required by prior art antifungal medications, my medication usually requires just one treatment to affect full cure. The effectiveness of my medication is nothing short of incremental, and is truly generations ahead of currently available antifungals. /->
  • plants of the pepper family, and plant species with similar chemistry contain active agents that provide complete cure when applied to areas infected with mycotic diseases. These agents may be administered in the wide range of commonly used drug vehicles and carriers, with results that are absolutely unprecedented when compared to prior art treatments.
  • Tinea in its various forms, otherwise known as athlete's foot, jock itch, favus, and ringworm, along with other types of dermatomycoses such as Candida, may be completely healed after a single treatment with my medication.
  • Topical treatment of these diseases in the form of an infusion, bath, douche, shampoo, lotion, drops, tincture, plaster, powder, aerosol, or other carriers, all provide outstanding results.
  • Antifungal drugs such as amphotericin B, clotrimazole, griseofulvin, ketoconazole, miconazole, nystatin and others, in addition to being expensive and time consuming, have many bad side effects that can further endanger the health of the patient.
  • These drugs taken internally, carry the risk of damage to liver and other internal organs, and adverse effects upon blood chemistry. Patients receiving such treatments must be monitored for changes in blood and organ function, as a safeguard against serious damage that can result from treatment.
  • Prior art systemic antifungals also interact adversely with a large number of other medications, another area that requires close attention by the attending physician. Beside this, other adverse effects include nausea, vomiting, diarrhea, fever, headache, and other unpleasant symptoms that accompany the discomfort of the disease.
  • Topical applications of my treatment generally require less active agents, than what might be commonly consumed in a meal that includes any of the pepper species. In addition to that, there is no long term, chronic exposure to the medicine, as is required with prior art topical antifungals, that have only a long term therapeutic effect, if any at all!
  • the prophylactic action of pepper constituents continues to protect damaged tissue from reinfection, by maintaining its antifungal action for days after treatment, in addition to it's direct, and immediate fungicidal action. This further aids rapid healing, by allowing diseased tissue to regenerate, rather than concentrate energy on combating disease
  • Pepper also appears to act as an immunostimulant, by precipitating leukocytes, and other mononuclear cells, along with a variety of antifungal compounds from the blood, and surrounding tissue, to the area of infection. Though done primarily through inducing inflamation, pain and discomfort are not required in order to receive the full therapeutic benefit. Pepper compounds are also believed to aid in the delivery of these antifungal immune resposes of the body, and increase their potency in addition to its own antifungal actions.
  • the infant has developed approximately six ringworm lesions about the back of the scalp, and back, and right side of the neck. The first few lesions were noticed a month before.
  • the mother of the infant has about six ringworm lesions on the right arm, most on the outside bicep. The appearance of the lesions was first noticed approximately three months before.
  • the father of the infant has approximately eight ringworm lesions on the left arm, most on the outside bicep.
  • the right arm has four lesions, also on the outside of the bicep. Four other lesions appear on the shoulders, and lower back. The man first noticed lesions of this type approximately eight years earlier.
  • the ringworm lesions have the same general appearance.
  • the lesions are ring shaped, with slightly raised outer borders that are sometimes crusty.
  • the lesions are red, with a smooth, and sometimes scaly interior.
  • a clear, sticky fluid sometimes covers the lesion.
  • the average diameter of the ring is about 15mm (.6"), with some as large as 20mm (.8").
  • the lesions appear, and remain for several weeks, sometimes disappearing, leaving lighter colored skin at the site of the prior lesion.
  • the man is first to be treated with a preparation of capsicum, wherein a plaster is applied to three lesions on the left bicep. A very slight, momentary tingling sensation is reported. The sensation lasts for about the first five minutes after application, and is not uncomfortable.
  • the plaster is left on the skin for about one hour, then rinsed off with water. Afterward, the lesions appear redder than they did prior to application of plaster. After six hours, the lesions appear to be whiter, with the coloration being more similar to the skin tone of the healthy skin, than prior to treatment. At twenty hours, all three lesions appear healed, as it requires very close examination to reveal the site of the prior lesion. The characteristic patch of lighter colored skin that normally accompany lesions that have healed by themselves is not present.
  • the infant girl is also treated with the capsicum plaster in the same manner as both her parents, and is healed in the same way, with the disappearance of all lesions within about one day. It is also interesting to note that the infant girl displays no sign of discomfort when the medication is applied, and does not cry, or even appear to take notice of the treatment.
  • the woman soaks her feet in a bath, prepared from infusion of capsicum, for fifteen minutes. The woman reports a warm, tingling sensation that lasts about ten minutes. This treatment is administered at 8:00 p.m.. The woman retires for the evening at 10:00, and does not experience any of the itching characteristics of the previous evenings. For three weeks the woman reports not a single recurrence of the itching on the feet. She continues to wear the same footwear as before, and does not take any kind of sanitary, or other precautions to avoid reinfection.
  • the woman's feet are treated with a lotion of capsicum, using raw aloe vera gel as the lotion carrier. Lotion is applied to the feet, and rinsed off with water at the end of half an hour. The treatment is administered at 8:00 in the evening, before the woman retires for the evening at 10:00. The woman reports no itching that evening, nor afterwards, for many months. She disposes of the comfortable shoes, she had bought for work, and has no further recurrence of athlete's foot symptoms. The woman is completely healed of athlete's foot after just one single treatment with my medication!
  • the sixth case involves a five year old girl, who is completely healed of a recalcitrant case of dry athlete's foot. Prior to treatment, the child's feet are peeling severely in the areas between the toes, and on the entire sole of the foot. Loose skin, in pieces as large as about 4mm (1/8") square are hanging around the lower edge of the ball of the foot. The entire sole of the foot is calloused, and has a wrinkled appearance. /7
  • Deep cuts occur periodically on the ball of the foot and around the base of the toes, particularly the great and small toes.
  • the child often complains that her feet hurt from the cuts, but oth. r /ise describes no other discomfort or symptoms.
  • the gi ⁇ has had these symptoms for about three years, since age two years.
  • the feet are nearly, completely healed. There are no cuts or scabbed cuts, and no pealing or loose skin. The callouses are nearly, completely reduced, and the skin has a healthy color /S and texture, and no longer has a wrinkled, ragged appearance. It is not possible to determine that the girl has ever had athlete's foot, as her feet are healthy and normal. The child is excited that her feet are "like new again”.
  • the girl's feet have returned to the pretreatment condition.
  • the skin on the sole of the feet is thickened and calloused.
  • the skin on the soles and between the toes is peeling and has a ragged appearance. Cuts appear periodically at the base of the toes, on the heel and at the ball of the foot. The dry athlete's foot is back in full force.
  • the girl's feet Prior to treatment, the girl's feet have again returned to their original, recalcitrant condition that was noted prior to the first treatment.
  • the girl's feet are peeling severely on the bottom and sides of the toes, and on the ball of the foot.
  • the skin in this area is thickened, and calloused, with deep cracks sometimes resulting in painful cuts.
  • the skin has a wrinkled, dry, and ragged appearance, with intermittent red blotches, occupying about half the total surface area. Small cuts appear periodically around the base of the great and small toes, which often cause pain, especially when walking.
  • capsaicin consisting of about .03 percent capsaicin (from oleoresin) in turpentine oil is applied to the right foot. There are no cuts on the right foot at this time, and the girl reports no discomfort from the medication.
  • a woman of sixty is cured of a dry variety of athlete's foot. Prior to treatment, the woman's feet have peeling skin between the toes, and thickened soles with cuts on the underside of the heal.
  • the woman's feet are soaked in a capsicum tea for fifteen minutes at a time, once a day, for five days. On the second day, the woman complains that her feet are very dry, and that one of the cuts on her heel is making walking difficult because of the pain. By the fourth day, she indicates the cessation of those symptoms. After eight weeks, the feet are examined and the skin appears healthy, with no sign of peeling or thickening of the skin. The woman indicates that after the fourth day of treatment, she did notice the reimmergence of symptoms at the time of the eight week examination, and felt cured since.
  • a skin scraping sent to a laboratory reveals the presents of fungal hyphae, not of the ringworm variety.
  • the boy is given griseofulvin orally, but must discontinue treatment after one week as a result of severe nausea.
  • the boy is then given tolnaftate topically, and has shown no significant improvement in the condition over a period of several weeks.
  • the boy is then given lotion prepared with capsicum, and instructed to apply the medication once every other day after bathing until symptoms disappear. All other treatments are also discontinued.
  • the treatment is discontinued after only two weeks, and the boy is healed without relapse after many weeks of observation even until the time of this writing.
  • the active principals found within capsicum, and piper species, and related families provide an important research tool in the systemic treatment of deep tissue mycoses, such as aspergilliosis, actinomycosis, nocardiosis, cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, entomophthoromycosis, candidiasis, and others.
  • Pepper extracts may be given by injection into the blood, spinal fluid, or directly into diseased tissue. Analogs of these active constituents may be developed for cral administration, however, some modification of t.-e molecular structure may be required to prevent decomposition of the active agents that occur as a result of digestive processes.
  • Pepper on the other hand, being itself a food compound consumed by man, is good for the body, not harmful as the prior art antifungals can be. All of centuries, throughout the world has used these plants for food, and from long experience of thousands of years, knows them to be safe and healthful to the body. Pepper compounds, being far less toxic than prior art antifungals, will not induce further illness in the patient, like prior art treatment, as dosages are usually less than the amounts commonly eaten at one time by those who enjoy the fruit, or spice.
  • Solanacea, piperacea, and related species of plants are widespread throughout the world, and are grown in virtually every country of the world. Their active constituents have all been synthesized, and some can be obtained very cheaply from existing commercial sources. Pepper extracts are versatile, and work very well in all conventional drug vehicles and carriers, allowing for the maximum amount of product embodiments.
  • a medication such as put forth by the current invention, counters this trend of escalating health care costs being economically, as well as medically therapeutic. It is very safe, and of unprecedented effectiveness. It provides far more complete, and rapid cure of disease than prior art medications, and at a cost of just pennies on the dollar.
  • the concepts set forth by the invention further serve as a model by which government medicaid, and medicare programs would save hundreds of millions of dollars each year in expenditures. Nationally, the total savings in Gross National Product for the United States could exceed 20 billion dollars annually if the treatment for dermatophyte infections alone were fully implemented.
  • Fig. 1 is a molecular diagram, of phenol.
  • Fig. 2 - 13 show molecular diagrams of compounds of the current invention ' .
  • Fig. 2 is a molecular diagram of ortho-methoxyphenol.
  • Fig. 3 is a molecular diagram of vanillyl.
  • Fig. 4 is a molecular diagram of
  • Fig. 5 is a molecular diagram of vanillylamide.
  • Fig. 6 is a molecular diagram of the capsaicinoids.
  • Fig. 7 is a molecular diagram of piperidine.
  • Fig. 8 is a molecular diagram of the pungent alkaloid principals of pepper.
  • Fig. 9 is a molecular diagram of eugenol
  • Fig. 10 is a molecular diagram of curcumin.
  • Fig. 11 is a molecular diagram of gingerol.
  • Fig. 12 is a molecular diagram of resiniferatoxin.
  • Fig. 13 is a molecular diagram of tinyatoxin. «£/
  • Fig. 14 - 25 show molecular diagram of common prior art antifungal drugs.
  • Fig. 14 is a molecular diagram of amphotericin B.
  • Fig. 15 is a molecular diagram of nystatin.
  • Fig. 16 is a molecular diagram of griseofulvin.
  • Fig. 17 is a molecular diagram of tolnaftate.
  • Fig. 18 is a molecular diagram of ciclopirox.
  • Fig. 19 is a molecular diagram of imidazole.
  • Fig. 20 is a molecular diagram of clotrimazole.
  • Fig. 21 is a molecular diagram of miconazole nitrate.
  • Fig. 22 is a molecular diagram of econazole nitrate.
  • Fig. 23 is a molecular diagram of triazole.
  • Fig. 24 is a molecular diagram of fluconazole.
  • Fig. 25 is a molecular diagram of terconazole.
  • a medicinal preparation of pepper, and its active constituents may be administered in a wide range of conventional drug vehicles and carriers.
  • Capsicum, and black pepper are available commercially as oleoresin, in a wide range of concentrations, and pungencies, and may be used in place of the plant product described below.
  • pepper or “pepper compounds” are used somewhat generically to indicate a "pungent botanical”.
  • Other botanicals such as those of the Zingiberacea family including ginger (Zingiber officinale), turmeric (Curcuma longa), cardamon (Elettaria cardamomum) , Melegueta pepper (Aframonum melegueta), members of the Euphorbia genus including Euphorbia resinifera, poinsetta (Euphorbia pulcherrima) , clove (Eugenia aromatica) , allspice (Pimenta officinalis) and others having similar constituents may be prepared in the same way as pepper by following the general procedures outlined below in the capsicum pepper illustration below.
  • the individual compounds responsible for the pungent quality of red peppers, and other capsicums may be obtained directly from ground red pepper, according to procedures described in the article "Separation and Quantitation of Red Pepper Major Heat Principals by Reverse Phase High-Pressure Liquid Chromatography" by Patrick Hoffman et. al., in the Journal of Agricultural Food Chemistry 1983, Vol. 31, pages 1326 - 1330.
  • the major capsaicinoids (fig. 6) include:
  • Nonanoic acid vanillylamide C 17 H 2q 0,
  • capsaicinoids are identified in research literature as trace elements within capsicum, and may be used in medicinal preparations as well, along with other analagous compounds.
  • Capsaicinoids may be generally classified as acid amide derivatives of phenol (fig. 1). The characteristic pungent, irritating sensory effects of these compounds are typical of acid amides, whether derived from phenol, or piperidine (fig.7).
  • Phenol (fig. 1), though lacking pungent flavor, is highly corrosive, caustic, and toxic, deriving many of its properties from its basic benzene structure. While this gives phenol certain antimicrobial properties, it is generally considered to be unsuitable for therapeutic use in man, and animals, due to it's high toxicity, and irritating effects on tissue.
  • methoxyphenol With the addition of a methoxy goup (OCH-.) to phenol, methoxyphenol is formed.
  • OCH-. methoxy goup
  • fig. 2 ortho-methoxyphenol
  • the effect of this methoxy group in part is an increase in aromacy, and a decrease in toxicity, and caustic properties otherwise existing in phenol, yet without apparent decrease in antimicrobial properties.
  • the attachment of hydrocarbon groups to the ring structure, to form higher analogues apparently increases the antimicrobial properties of ethoxyphenol, and phenol. It is presumed that the meta, or para isomers of methoxyphenol have similar properties to the ortho, in like manner to the similarities between the phenol isomers.
  • the vanillyl structure on which the capsaicinoids are constructed is also typical of the pungent principals found in ginger (zingiberacea) species of plants.
  • gingerol Collectively known as gingerol (fig. 11): shogaol, paradol, zingerone, gingerol and other analogs, have a different side chain than the capsaicinoids, and lacking an ammonia (NH ) group, are neither amines, or amides like the capsaicinoids or piperidines. Hydrolysis of gingerols yield vanillyl, and a fatty acid side chain, both of which demonstrate like therapeutic properties to the capsaicinoid hydrolytes.
  • NH ammonia
  • turmeric (Curcuma longa L. ) contains the compound curcumin (fig. 10), actually a vanillal derivative differing from vanillyl by one hydrogen (H) atom having an (CH) substituent, rather than a methylene (CH_) in the para position.
  • This analog differs further with a side chain unique from the others. Cardamon, allspice, clove, black pepper, and many others contain eugenol, another vanillyl analog with yet another I ; 'rocarbon side chain.
  • this organic hydrocarbon group is a chain acid (R'), varying from about 8, to 14 carbon atoms, depending upon the particular capsaicinoid.
  • the piperidines represent a group of analogous alkaloid compounds from which most of the pungent principals found within plants of the piperacea family, of which black pepper (piper nigrum) is a member, are found. Also classified as acid amides, the piperidines, like the capsaicinoids found in capsicum species, are primarily responsible for the characteristic sharp, pungent taste of black pepper.
  • the piperidine ring (fig. 7) structure is diverse from that of phenol (fig. 1). Though also a six membered, carbocyclic compound, piperidines instead contain one nitrogen (N) hetero atom within the ring. Piperidine is heteroparaffinic, and contains no double bonds. The hetero nitrogen atom within the ring is a contributor to the pungency of these compounds.
  • the attachment of a hydrogen (H) atom to the hetero nitrogen atom within the ring forms the amine structure.
  • Attachment of a hydrocarbon group, in the form of a side acid chain (R" fig. 8) attached to a benzene structure establishes the acid amide structure.
  • These compounds include; piperine C-, 7 H 1 g N0 3 (fig.
  • Chavicine for example is hydrolysed to piperidine, which receives an additional hydrogen (H) atom to form a primary amine, and chavicic acid, which receives the hydroxy (OH) group to form the fatty acid.
  • Hydrolysis of these capsaicinoid, and piperidine acid amides, as well as the other listed compounds may be accomplished with chemical catalysts, or by boiling a liquid preparation of these compounds with water. Hydrolysis does not appear to diminish the pungency of these compounds, and in some cases actually appears to enhance both their pungency, and therapeutic action.
  • the carbonyl group (C 0) side chain substituent, common to all the above compounds (except eugenol) is also believed to be a contributor to antimicrobial activity.
  • the newer triazole (fig. 23) class includes fluconazole (fig. 24), terconazole (fig. 25), itraconazole, and others.
  • capsicum Other active agents found within capsicum include citric acid, vitamins A, B. , B , C, and E, iron, potassium and niacin in significant quantities, along with other lipids, and carotenoids including capsanthin, capsorubin, and others.
  • An infusion of pepper may be prepared by soaking
  • Infusion should be allowed to soak at least ten minutes before use for best results. According 'to preference, infusion may, or may not be strained to remove plant residue before use.
  • a tea of is a more potent version of infusion above, using about 16 cm (1 teaspoon) of ground pepper for each liter (quart) of sensibly comfortable water. Tea may also be prepared from boiling water, or itself be boiled in water before use. Boiling pepper in water assures complete hydrolysis of the pungent principals, which are also active agents.
  • a tincture may be prepared by soaking ground red, or black pepper in a solution containing approximately 60% ethanol, and 40% water. Pure ethanol, and other solvents such as acetone, chloroform, vinegar (acetic acid), and others may also be used.
  • the fluid volume of the solution may be about three, or four times that of the dry volume of the ground pepper.
  • a preparation of pepper drops may be obtained by reducing tincture through heat, or passive evaporation. Drops made by this method are similar in purity to some grades of commercially available oleoresin of capsicum, and black pepper.
  • a plaster, or poultice may be prepared by mixing ground pepper with water, until it has a paste-like consistency that will assure good adherence to the skin, or cloth to which it is applied.
  • a lotion, cream, or shampoo may be obtained by adding to any commercially available shampoo, cream, or lotion, a portion of drops, or tincture equal to approximately 25% of the volume of lotion, cream, or shampoo carrier.
  • a douche is prepared from infusion, or tea that is strained of the plant residue material before use.
  • a suppository is made from drops in cocoa butter, or gelatin in the same strength as douche, or lotion.
  • An injection is prepared from a purified version of infusion, tea, drops, etc., administered intravenously, in tissue, or mixed with, and injected into the spinal fluid.
  • a powder is pepper in ground form, or extracts mixed, and/or bound within a binding powder carrier such as talc.
  • Pepper, and any of its active constituents may be administered as a general antiinfective in the treatment of disorders including fungal, and bacterial infections.
  • Pepper extracts may be administered within conventional drug vehicles, and carriers, and are recommended for use in four basic concentrations. £ ⁇ ?
  • Recommendations for treatment given below are general, and may be altered to suit specific conditions. If one recommended concentration for some reason appears unsuitable, the next graduation should be used.
  • an infusion may be used in the treatment of milder microbial infections including dermatophyte infections, particularly when tissue damage is minimal. Infusion works well as a scalp rinse, a bath for the feet, and skin, and as a douche in the treatment of Candida, and other vaginal disorders. Infusion is also recommended if patient sensitivity to the higher concentrations becomes significant.
  • a tincture, a powder, a poultice, and a preparation of drops are recommended in the treatment of severe dermatophytosis.
  • High concentrates such as these, are preferred where tissue damage is significant, and where infection sites are causing considerable discomfort for the patient.
  • Drops work well for topical treatment of nail infections, ringworm lesions, and infected hair.
  • These high concentrates generally produce cure after the first dose when treating skin lesions, and have a prophylactic action of greatest duration, lasting up to about five days after application. As it is usually necessary to induce substantial healing of the skin as a measure against recontamination, and reinfection of dermatophytes, the higher concentrates appear to be most effective as prophylactics as well.
  • a tea represents a moderate concentration of pepper compounds. It may be used in the same manner as infusion, or in the treatment of more severe cases of dermatophytosis. Tea should be used if infusion fails to bring immediate relief of secondary symptoms, such as itching in athlete's foot, Candida, or jock itch, within one hour of the first treatment.
  • Tea may also be used in place of the higher concentration carriers, such as drops or tincture. It is often equally effective in curing severe cases of dermatophytosis, in which there is significant tissue damage, as the high concentrates. In this case, tea is preferred over the high concentrates, particularly if the patient sensitivity to the medication is causing significant discomfort.
  • Tea is also suitable as a gargle, or mouth rinse for thrush, or other fungal infections of the throat, and oral cavity.
  • a lotion, or shampoo may be prepared with any commonly available lotion, or shampoo, and applied to infected areas in its intended manner.
  • Other therapeutic agents in addition to pepper extracts, may be added to shampoo and lotion.
  • a topical anesthetic such as lidocaine, or benzocaine may be added to lotion to reduce severity. If skin is very dry, emollients may also be added to lotion.
  • a pepper aerosol may be inhaled in the treatment of throat, and respiratory infections.
  • aerosol should be derived from a lower concentration such as infusion, as pepper is extremely irritating to the nose, throat, lungs, and eyes, especially when airborne. This is especially true of capsicum aerosol. For this reason, aerosol is somewhat limited in it's medicinal application.
  • the irritating effects of pepper aerosol, and particularly capsaicum, is greater when distributed within an etheric tincture solution, such as alcohol, ether, chloroform, or acetone. Once airborne, even minute concentrations have a tear gas, or macelike effect on the eyes, and respiratory system.
  • a cayenne pepper ethanol tincture (60% ethanol/40% water works well) aerosol from a hand held dispenser is sufficient to render a fifteen hundred square foot enclosed area uninhabitable to humans, and animals, as choking, coughing, and burning irritation to the eyes and respiratory system make habitation of the room intolerable.
  • Pepper powder is also very irritating when airborne, and like aerosol, has a more limited medical application than the other carriers. If used as a foot powder for example, it is best to fix the pepper compounds within a powder binder such as talc, to prevent, or lessen escape of airborn particulate.
  • a powder binder such as talc
  • the first therapeutic action of pepper extracts upon administration is that of an irritant, or as I prefer to call an inflamatory.
  • the irritant constituents of capsicum namely the capsaicinoids (fig. 6), their hydrolytes, and the other acid amide piperidines (fig. 7 & 8), and their hydrolytes found in black pepper, and related compounds are all instrumental in precipitating a rapid inflamatory response in the area of administration. This is observed, for example, when applied to skin in the treatment of various forms of tinea. The area of treatment often turns red, or pink, and feels warm or hot. Burning, or warm tingling is sometimes reported by patients after topical administration of pepper extracts, usually the result of excessive dosage, or exposure to open cuts in tissue.
  • the therapeutic value of inflammation is the stimulation of the body's own immune response in the ⁇ s. area of infection. This precipitates a varied array of fungistatic serums, including leukocytes, and other mononuclear cells in the area of infection. These fungistatic serums inhibit the growth of pathogenic fungi.
  • Inflamation also increases the rate of skin shedding, which combats penetration of the fungus, or other organism into the skin.
  • the microbe In this mode of action, the microbe is essentially "cast off" with the diseased tissue. Perhaps or this reason, those varieties of dermatophytosis that are accompanied by inflamation often eventually heal on their own.
  • the noninflamatory varieties such as dry athlete's foot, however become chronic, and are very difficult to heal. The lack of participation of the immune responses of the host prevents healing, and cure.
  • Pepper compounds are believed to act as an adjuvant to these fungistatic serums, by facilitating their pathways through the blood vessels, and skin of the host, and through the cell wall of the fungi, or other pathogen. Being composed primarily of lipids, capsicum for example is believed to increase the permeability of the cellular walls of both the host, and fungi. In addition to aiding the delivery of antifungal serum, the increase in cell wall permeability also facilitates the delivery of undecylenic acid, another antifungal compound found in sweat, into the fungi. With the aid of increased permeability provided by pepper compounds, these antifungal compounds, which are normally fungistatic, become fungicidal.
  • the direct antimicrobial properties of pepper and another of the notably pungent botanicals ginger may be observed in vitro, in addition to those observed in vivo in the actual treatment of disease.
  • Example A A series of in vitro tests are conducted on 3 tincture samples prepared from the ground spice of cayenne pepper (Sample A), black pepper (Sample B), and ginger (Sample C) . Each spice is measured, and mixed with pure ethanol in an amount three times the measured volume. The mixtures are stored for 18 hours at room temperature (22°C), and agitated on 5 separate occassions over the period. The mixtures are then strained of residue, and submitted for testing. Also included is Sample F; a tincture prepared with commercially pure capsaicin (8-methyl-N-vanillyl-6-nonenamide) at a concentration of 25mg./ml. pure ethanol.
  • Samples A, B, C, & F of the current invention show greatest activity against those fungal strains most resistant to the drug standard Amphotericin B!
  • C. albicans ATCC 38247, C. kefyr ATCC 28838, and T. glabrata ATCC 15545 show particular sensitivity to Samples A, B, C, & F in this screen.
  • capsaicin though the most toxic compound found in any significant amount in capsicum peppers, is much less toxic than Amphotericin B!
  • Sample F has a concentration of pure capsaicin at 25 mg./ml. - about 40 times the total capsaicinoid content of Sample A, yet is still short rX of the Sample A performance accross the board!
  • This can only mean the presence of another antifungal compound, and/or a synergistic relationship between the mix of capsaicinoids and other compounds within the botanical that account for the total antimicrobial effect.
  • the therapeutic actions of these botanicals are not generally improved by extensive isolation of their individual constituents, and that the total therapeutic mechanisms involved are quite complex, involving a substantial number of compounds in addition to the phenols, and piperidines present. In this respect, high purification of individual constituents has the undesireable effect of to some degree dismantling the full therapeutic action of the compound.
  • Sample F is the exception containing a purified isolate (capsaicin) of the primary pungent principal found in red pepper and other capsicums. Sample F also has perhaps 3 times the capsaicinoid, and 6 times the capsaicin content of the most pungent species of capsicum known to exist in nature. Yet accross the board. Sample F falls short of the basic botanical extract Sample A even though it has 40 times the capsaicinoid concentration of Sample A!
  • phytoalexins Other possible antimicrobial agents found in pepper plants, that may play a role in producing curative results, are known as phytoalexins.
  • Phytoalexins such as the compound capsidiol, found in plants of the solanacea family which includes capsicums, are a group of antimcrobial agents, not normally present in the plant, that are produced by the plant, only in response to trama caused by heat, cold, mechanical injury, or attack by insects, or microbes.
  • Capsidiol, and other of the phytoalexins produced by solanacea species are known to have antifungal properties against fungi that are pathogenic to solanacea species of plants.
  • capsidiol, or another ph toalexin produced in response to their challenge has antifungal action against fungi that are pathogenic to man, as well as those pathogenic to plants. It is therefore possible that capsidiol, or another phytoalexin may play a role in curing fungal disorders in man and animals, as well as plants.
  • Dehydration is another possible therapeutic action of pepper compounds.
  • pepper extracts appear to dry the skin to a degree that may be inhospitable to fungi. Perhaps the result of increased permeability, or the formation of salts on the skin, the skin, though drier, is not ? uncomfortably so, and may have at least a fungistatic effect as a result of reduced hydration.
  • pepper extracts are another important therapeutic feature of the current invention.
  • pepper compounds In addition to having immediate fungicidal action in the treatment of superficial mycoses, pepper compounds remain in the skin for perhaps ten days after treatment, to prevent reinfection. Patients often report the reoccurrence of the warm, tingling sensation in treated areas while bathing, days after treatment. Exposure to water appears to also restimulate its therapeutic action as well. If feet, or skin become moist, and sweaty, the therapeutic action is intensified, at the same pathogenic fungi would otherwise proliferate. This provides a shield against reinfection due to recontamination, and protects the skin while it heals.
  • Pepper compounds also function as a vulnerary, aiding, and accelerating the healing and regeneration of tissue.
  • tissue damage can be severe in certain forms of dermatophytosis, such as favus, nail infections, and athlete's foot, it becomes necessary to heal the damaged tissue before full cure is possible.
  • Pathogenic fungi finding opportunity in damaged skin for example, will often continue to reinfect those areas unless the skin is healed. This is one reason prior art medications are so ineffective towards cure. It becomes necessary to heal the skin to safeguard against repeat infection, as healthy, whole skin is the best protection against reinfection.
  • capsicumfor example is particularly high in vitamins, and other nutrients, they also appear to have a healing effect on damaged tissue.
  • a medication such as described above is an invaluable wound healing treatment, particularly for the immune suppressed, and should be used to treat cancers, and other neoplasms.
  • Pepper compounds are also unbelieveably effective in the treatment of burns, and abrasions. On several occassions I have treated burns with pepper lotion with results as incremental as with lacerations. The improvement in the healing of the skin is quite notable within hours, with continued improvement in the following days that is nothing short of astonishing. This also is very important to burn patients, and is likely to excellerate recovery to a degree that will save the lives of many that would otherwise die from their injuries.
  • Pepper compounds could be injected into deep tissue to excellerate the healing of buises and contusions. This would be of great benefit to athletes, and accident victims.
  • pepper compounds are perhaps due to the high concentration of antioxidant compounds such as vitamin E, aromatic amines, phenols, and amino phenols found in pepper, particularly capsicum. These antioxidants may interfere with the action of digestive enzymes secreted by the fungi, .that are necessary for ingestion of nutrition, in effect starving the fungi. It is also possible that high concentrations of citric acid, or vitimins found in pepper, are directly toxic to the fungi.
  • vitamin C a known oxidant
  • the very high concentration of vitamin C may also interfer with the ability of the fungi to digest, and ingest nutrition, by instead oxidizing it's food compounds before they can be absorbed, also depriving the fungi of food.
  • capsicum is so high in vitamin A, the B complex, C, D, and E, it can be used to treat several nutritional disorders including scurvy, pellagra, beriberi, rickets, xerophthalmia, and a host of related diseases.
  • Significant amounts of iron, and potassium make it excellent for correcting fluid absorption, and retention imbalances that result from dehydration due to diarrhea, and vomiting.
  • Infusion or tea of capsicum may be given to correct dehydration due to diarrhea. Soaking the ground powder only briefly in cool water, to produce a cold tea, or infusion should be sufficient to release the water soluble C, and B vitamins, and mineral salts, without releasing as many of the pungent principals, which may make ingestion difficult.
  • Pepper compounds also appear to possess keratolytic actions, which aid healing of these general forms of dermatitis, by aiding in the breakdown of keratin in the skin. This also makes them useful in the treatment of warts, corns, callouses, acne, wrinkles, and cancers. Keratolytic action may also have an antimicrobial effect, by perhaps interfering with the ability of pathogenic microorganisms such as fungi to digest, or ingest the keratin on which they feed.
  • pathogenic microorganisms such as fungi to digest, or ingest the keratin on which they feed.
  • a four year old girl, with chronic seborrhea of the scalp was completely healed of the disorder after just three treatments with capsicum drops. The girl has two lesions, approximately 25mm (1") diameter on the top portion of her scalp, that she has had since infancy. The lesions are tightly packed with thick, yellowish white scales approximately 2mm (1/16") in diameter. The area above the lesions is covered with loose scales
  • the two seborrhea lesions are treated topically, with capsicum drops, prepared from heat evaporated tincture.
  • the dosage is once a day for three consecutive days.
  • Another illustration of the keratolytic properties of pepper compounds involves a 12 year old boy, afflicted with a large plantar wart on the heel of his foot, in which the boy is completely healed after a single treatment with a pepper extract.
  • the boy has a large, brownish colored plantar wart on the upper inside portion of the heel of his right foot.
  • the wart has caused the boy mild, to extreme discomfort, particularly when walking.
  • the wart has been treated with several over the counter, and physician prescribed topical medications that yield no noticable improvement in the condition.
  • the boy is accustomed to shaving the wart off at the skin surface at regular intervals to reduce the size, and hence the degree of discomfort associated with its rapid growth.
  • the wart continues to grow back causing the usual discomfort.
  • the wart Prior to treatment with pepper drops, the wart is examined, and appears to occupy a brownish, rough area of the heal approximately 25mm. (1") in diameter at the base. The central portion is raised, forming a nodule approximately 6mm. (1/4") above the skin surface.
  • the wart is treated topically with one (1) drop of pepper drops that were prepared from a standard 4:1 red pepper acetone tincture that was reduced 40 times by room temperature evaporation. Upon application, the boy reports no notable sensation from the treatment.
  • the current invention provides an antimicrobial treatment, with a degree of effectiveness in the treatment of fungal diseases that is many generations ahead of the prior art.
  • Naturally occuring compounds found in pepper plant species of the solanacea family, which include the capsicums C. frutescens, C. annuum, C. Baccatum, and the piperacea family which includes the peperoma, and piper genera, and the well known retrofractum, nigrum, and longum species among others, and related compounds, are found to have profound therapeutic actions in the treatment of fungal disorders. These compounds may be administered in most commonly used drug delivery vehicles, and carriers, with outstanding results.
  • a single topical treatment with my medication is all that is usually necessary to provide complete cure for most superficial mycoses including ringworm, inflamatory athlete's foot, jock itch and Candida.
  • the onset of effect is immediate, with cessation of symptoms usually within the first hour of treatment, and complete healing within the first few days.
  • Prior art systemic treatments which require the attendance of a dermatologist, and daily multiple doses of the medication over a period of several months, can cost hundreds of dollars to treat, and are often unsuccessful in providing complete cure.
  • prior art systemic antifungals have many adverse effects, which are not only unpleasant, but can themselves cause serious health problems.
  • the risk of damage to internal organs, blood composition and adverse interactions with other medications are factors that must be carefully weighed by physicians administering prior art systemic antifungals. With this, other less sever, yet unpleasant side effects include nausea, vomiting, headache, dizziness, fever, diarrhea, and many other disorders that contribute to the misery and ill health of the patient.
  • Pepper compounds are safe, being a food, consumed by man for thousands of years, and do not induce illness in the patient as prior art antifungals often do. Pepper is widespread throughout the world, and is grown in virtually every country. Its active constituents, most of which are pungent acid amide compounds, easily obtainable from the ground product, have all been synthesized, and many are available from commercial drug and chemical manufacturers.
  • the high effectiveness, low toxicity, and very low cost of My medication will greatly broaden the size of the veterinary market for treatment of mycoses.
  • the high effectiveness, low toxicity, and very low cost of my medicine also makes feasible the creation of a significant market for treatment of mycoses within the livestock industry. Being highly contagious, and finding opportunity under certain common weather conditions, dermatophytoses such as ringworm for example, can become epidemic within a herd, within a very short time, disqualifying them from sale at the feed lots.
  • Pepper, and it's active constituents provide an important research tool in the treatment of deep tissue fungal disorders, as well as the superficial varieties.
  • Pepper extracts may be given by injection into the blood, spinal fluid, or directly into diseased tissue for the treatment of aspergillosis, actinomycosis, crytococcocis, entomophthoromycosis, histoplasmosis, blastomycosis, coccidioidomycoses, paracoccidioidomycoses, candidiaisis, and other deep tissue fungal disorders.
  • Analogs of pepper's active constituent may also be developed for oral administration to prevent decomposition as a result of digestive processes.
  • Pepper's ability to induce an inflamatory response in the area of administration provides an important research tool for studying immunostimulation in the treatment of disease. Since inflamation precipitates a varied array of antifungal serums, including leukocytes, and other mononuclear cells to the site of infection, this antimicrobial effect is believed to play a major role in pepper's extremely success at curing microbial infections of the keratin layers. These properties are valuable in the systemic treatment of disease as well, and particularly so for immunocomprimised patients.
  • pepper extracts towards pathogenic fungi make it an excellent prospect for experimentation with other pathogens such as bacteria, in the development of new antiseptics and antibiotics.
  • Pepper's affinity for the skin also makes it a good candidate for the treatment of staphylococcus, and other bacterial infections of the skin. It's low toxicity also favors its use in the treatment of systemic bacterial infections including all types from ear infections to tuberculosis.
  • pepper compounds include clothing, and shoe liners made from capsicum wool, or any other fabric impregnated with pepper compounds as a safeguard against harboring these pathogens within one's clothing.
  • clothing and shoe liners made from capsicum wool, or any other fabric impregnated with pepper compounds as a safeguard against harboring these pathogens within one's clothing.
  • socks, or shoes with liners impregnated with pepper may be worn to prevent contamination leading to infection.
  • Pepper offers promise in a wide variety of agricultural applications as well. Crop fields may be sprayed or dusted with pepper preparations, or added to irrigation water to facilitate a variety of important operation.
  • the antimicrobial properties of pepper will protect the plant from fungal, bacterial, and viral disease. It will also protect harvested produce from spoilage. In these two respects, crop yield is increased, and allowable storage time extended, as microbes take a far less significant tole of the harvested crop.
  • Pepper's action as an irritant further serves increased crop yields by performing as a repellent for crop destroying animals and insects, in addition to acting as an insecticide.
  • capsicum preparations in particular perform like mace, or tear gas, producing extreme burning and irritation of the eyes, nose throat, lungs, and all mucous membranes in incredibly low concentrations.
  • Crops in fields treated with capsicum and related plant species will have an intolerably offensive taste and odor, that will repel rodents, birds, insects, and microbes that otherwise damage crops.
  • pepper preparations will act as a preservative by continuing to stem these destructive influences, even after delivery to market.
  • the irritating constituents of pepper are also useful for military and law enforcement purposes, as safe alternatives to mace and tear gas, in addition to their therapeutic, and agricultural uses.
  • an etheral solvent such as alcohol
  • capsicum pepper When dispersed in a fine mist, or vapor containing an etheral solvent such as alcohol, capsicum pepper in particular produces extreme, and intolerable irritation to the eyes, and respiratory system, along with uncontrolable choking, and coughing in the most minute dosages!
  • An invisible, and odorless vapor containing a single squirt from a typical fine mist cosmetic bottle containing cayenne pepper ethanol tincture is sufficient to render a fifteen hundred square foot room uninhabitable to humans.
  • tear gas-like canisters specially suited for the purpose, very large areas of atmosphere could be covered with very few distribution units.
  • Pepper derivatives whether used to treat crops, or livestock, are perfect for use in the food industry. Being itself a food compound, generally recognized as safe (GRAS) by the U.S. Food and Drug Administration, pepper will pose no health risks to consumers of these food products. Whether applied topically to livestock, or added to their feed, or injected as a systemic antibiotic, pepper derivatives will not raise crucial safety concerns, as all prior art systemics have.
  • GRAS safe
  • Other possible areas for investigating pepper and its derivatives include treatment of trees for Dutch elm disease, and other disorders, and treatment of rare painting and artifacts as a preservative, and as disinfectant, and as a treatment against parasitic worms.
  • pepper compounds in the treatment of tumors, cancer, and other diseases involving cellular mutation of tissue, along with immune disorders such as AIDS, has excellent prospects for the developement of many new drugs, and treatments.

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  • Alternative & Traditional Medicine (AREA)
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  • Dermatology (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract

L'invention concerne une nouvelle classe de composés généraux anti-infectieux extraits du poivre, du gingembre et d'autres espèces végétales contenant les structures cycliques de la vanillyle (fig. 3) et de la pipéridine (fig. 7), qui sont caractéristiques des principes âcres que l'on trouve dans le poivre et le gingembre. Ces structures, les groupes hydrocarbures qui y sont rattachés, et d'autres composés que l'on trouve dans l'extrait végétal sont utilisés pour le traitement local de la dermatophyte, des lésions de la peau et de la prolifération anormale de kératine.
PCT/US1993/004763 1992-05-21 1993-05-19 Usilisations therapeutiques de substances vegetales acres et des composes derives WO1993023061A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
GB9423318A GB2286120B (en) 1992-05-21 1993-05-19 Therapeutic pepper extracts and related compounds
US08/338,489 US6063381A (en) 1993-05-19 1993-05-19 Therapeutic uses of pungent botanicals and their related compounds
DE4392300T DE4392300T1 (de) 1992-05-21 1993-05-19 Therapeutische Gebräuche von beißenden Pflanzen und Ihre Verwandten Zusammensetzungen
US09/571,644 US6593371B1 (en) 1993-05-19 2000-05-15 Treatment for wart and related disorders
US10/620,794 US20050058729A1 (en) 1993-05-19 2003-07-15 Treatment for bacterial infections and related disorders

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US88664092A 1992-05-21 1992-05-21
US07/886,640 1992-05-21

Related Child Applications (1)

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US09/571,644 Continuation-In-Part US6593371B1 (en) 1993-05-19 2000-05-15 Treatment for wart and related disorders

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WO1993023061A1 true WO1993023061A1 (fr) 1993-11-25
WO1993023061B1 WO1993023061B1 (fr) 1994-01-06

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2758087A1 (fr) * 1997-01-09 1998-07-10 Daniel Jean Utilisation des gingerols pour la preparation de compositions deodorantes et antiseptiques et compositions les contenant
WO1998030201A1 (fr) * 1997-01-09 1998-07-16 Societe D'etudes Et De Recherches En Pharmacognosie - S E R P Utilisation des shogaols et des gingerols pour la preparation de compositions deodorantes
WO1998052884A1 (fr) * 1997-05-23 1998-11-26 Eran Nicodemus Bauer Vanillamide d'acide pelargonique renfermant du gaz lacrymogene
WO1998056356A1 (fr) * 1997-06-10 1998-12-17 Reckitt & Colman Products Limited Compositions therapeutiquement actives
US5925376A (en) * 1994-01-10 1999-07-20 Heng; Madalene C. Y. Method for treating psoriasis using selected phosphorylase kinase inhibitor and additional compounds
EP1112745A1 (fr) * 2000-01-03 2001-07-04 Irma Maestri Composition homéopathique
WO2001089571A2 (fr) * 2000-05-19 2001-11-29 Sabinsa Corporation Methode permettant d'augmenter la biodisponibilite de nutriments et preparations pharmaceutiques renfermant de la tetrahydropiperine et des analogues et derives de tetrahydropiperine
GB2455585A (en) * 2008-01-16 2009-06-17 Ali Reza Rezai-Fard Composition for treating a skin disorder
EP2014295A3 (fr) * 2007-06-04 2010-04-14 Velleja Research SRL Compositions topiques pour la prévention et le traitement d'états inflammatoires et/ou infectieux de la région génitale
WO2010062581A2 (fr) * 2008-10-27 2010-06-03 The Regents Of The University Of Michigan Composition botanique pour une réparation cutanée optimisée et utilisations associées
US11306051B2 (en) 2009-10-01 2022-04-19 L'oreal Use of vanillin derivatives as a preservative, preservation method, compounds, and composition

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI290469B (en) * 2000-07-12 2007-12-01 Medical & Pharm Ind Tech & Dev Method for manufacturing product with component capable of efficiently preventing inflammation and platelets agglutination form ginger and medical composition with the efficient component
DE102008009752A1 (de) 2007-10-09 2009-04-16 Jens Tannert Gesundheitsförderndes Mittel und dessen Verwendung

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* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 103, No, 25, issued 23 December 1985, G.M. SARKAR et al., "Antibacterial Studies with the Compounds Isolated from Piper Methysticum Forst", see page 519, the Abstract No. 2108869q; & NATL. ACAD. SCI. LETT., (India), 1985, 8(4), 109-10, (Eng). *
CHEMICAL ABSTRACTS, Volume 112, No. 19, issued 07 May 1990, M. NAIR et al., "Antimicrobial Piper Metabolite and Related Compounds", see page 406, the Abstract No. 175337y; & J. AGRIC. FOOD CHEM., 1990, 38(4), 1093-6, (Eng). *
CHEMICAL ABSTRACTS, Volume 97, No. 11, issued 13 September 1982, S. LINKE et al., "Synthesis, Spectroscopic Examination, and Testing for Antibacterial Activity of Some Pepper Alkaloids. Olefination Reactions with Phosphorylacetamides", see page 802, Abstract No. 92598e; & LIEBIGS ANN. CHEM., 1982, 6, 1142-9, (Ger). *

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5925376A (en) * 1994-01-10 1999-07-20 Heng; Madalene C. Y. Method for treating psoriasis using selected phosphorylase kinase inhibitor and additional compounds
US6264928B1 (en) 1997-01-09 2001-07-24 Societe D'etudes Et De Recherches En Pharmacognosie Use of shogaols and gingerols for preparing deodorant compositions
WO1998030201A1 (fr) * 1997-01-09 1998-07-16 Societe D'etudes Et De Recherches En Pharmacognosie - S E R P Utilisation des shogaols et des gingerols pour la preparation de compositions deodorantes
FR2758087A1 (fr) * 1997-01-09 1998-07-10 Daniel Jean Utilisation des gingerols pour la preparation de compositions deodorantes et antiseptiques et compositions les contenant
WO1998052884A1 (fr) * 1997-05-23 1998-11-26 Eran Nicodemus Bauer Vanillamide d'acide pelargonique renfermant du gaz lacrymogene
GB2337806A (en) * 1997-05-23 1999-12-01 Bauer Eran Nicodemus Pelargonic acid vanillylamide containing tear gas
GB2337806B (en) * 1997-05-23 2001-01-03 Bauer Eran Nicodemus Pelargonic acid vanillylamide containing tear gas
WO1998056356A1 (fr) * 1997-06-10 1998-12-17 Reckitt & Colman Products Limited Compositions therapeutiquement actives
GB2332147A (en) * 1997-06-10 1999-06-16 Reckitt & Colmann Prod Ltd Therapeutically active compositions
GB2332147B (en) * 1997-06-10 1999-10-27 Reckitt & Colmann Prod Ltd Therapeutically active compositions
US6201014B1 (en) 1997-06-10 2001-03-13 Reckitt & Colman Products Limited Therapeutically active compositions
EP1112745A1 (fr) * 2000-01-03 2001-07-04 Irma Maestri Composition homéopathique
WO2001089571A2 (fr) * 2000-05-19 2001-11-29 Sabinsa Corporation Methode permettant d'augmenter la biodisponibilite de nutriments et preparations pharmaceutiques renfermant de la tetrahydropiperine et des analogues et derives de tetrahydropiperine
WO2001089571A3 (fr) * 2000-05-19 2002-03-07 Sabinsa Corp Methode permettant d'augmenter la biodisponibilite de nutriments et preparations pharmaceutiques renfermant de la tetrahydropiperine et des analogues et derives de tetrahydropiperine
GB2380675A (en) * 2000-05-19 2003-04-16 Sabinsa Corp Method of increased bioavailability of nutrients and pharmaceutical preparations with tetrahydropiperine and its analogues and derivatives
GB2380675B (en) * 2000-05-19 2004-11-03 Sabinsa Corp Method of increased bioavailability of nutrients and pharmaceutical preparations with tetrahydropiperine and its analogues and derivatives
EP2014295A3 (fr) * 2007-06-04 2010-04-14 Velleja Research SRL Compositions topiques pour la prévention et le traitement d'états inflammatoires et/ou infectieux de la région génitale
GB2455585A (en) * 2008-01-16 2009-06-17 Ali Reza Rezai-Fard Composition for treating a skin disorder
GB2455585B (en) * 2008-01-16 2010-07-28 Ali Reza Rezai-Fard Capsicum seeds for the treatment of eczema and dermatitis
WO2010062581A2 (fr) * 2008-10-27 2010-06-03 The Regents Of The University Of Michigan Composition botanique pour une réparation cutanée optimisée et utilisations associées
WO2010062581A3 (fr) * 2008-10-27 2010-08-19 The Regents Of The University Of Michigan Composition botanique pour une réparation cutanée optimisée et utilisations associées
US11306051B2 (en) 2009-10-01 2022-04-19 L'oreal Use of vanillin derivatives as a preservative, preservation method, compounds, and composition
US11691937B2 (en) 2009-10-01 2023-07-04 L'oreal Use of vanillin derivatives as preserving agents, preserving process, compounds and composition

Also Published As

Publication number Publication date
DE4392300T1 (de) 1995-12-07
CA2136174A1 (fr) 1993-11-25
GB9423318D0 (en) 1995-02-15
GB2286120B (en) 1997-01-15
GB2286120A (en) 1995-08-09
AU4382693A (en) 1993-12-13

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