WO2008136012A1 - Oral medicinal preparations - Google Patents

Oral medicinal preparations Download PDF

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Publication number
WO2008136012A1
WO2008136012A1 PCT/IN2007/000253 IN2007000253W WO2008136012A1 WO 2008136012 A1 WO2008136012 A1 WO 2008136012A1 IN 2007000253 W IN2007000253 W IN 2007000253W WO 2008136012 A1 WO2008136012 A1 WO 2008136012A1
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Prior art keywords
capsaicin
mixture
formulation
solvent
extract
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PCT/IN2007/000253
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French (fr)
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Rajesh Shah
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Rajesh Shah
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/81Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids

Abstract

A formulation comprising a potentized mixture of an extract of capsaicin and an extract of dihydrocapsaicin in a ratio of about 50 : 1 to about 1 : 50 in a solvent where the ratio of combined extract to solvent ranges from about 0.5 to 100 to about 2 :100.

Description

ORAL MEDICINAL PREPARATIONS

FIELD OF INVENTION

This invention relates to oral medicinal preparations.

In particular, it relates to homeopathic medicinal preparation from plant material.

DEFINITIONS

As used in the present specification, the following words and phrases are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise.

Homeopathy is a system of alternative medicine that aims to treat "like with like." Homeopathic formulae are based on the theory that even when a remedy is diluted with water to the point where no starting material remains, then also it is very effective clinically.

Potentization in homeopathy is a process making a remedy more potent by serial dilutions (even to the extent that it is unlikely to contain a single molecule of the original substance) with powerful shaking by giving strokes, is called Potentization in the science homeopathy.

Potency means capacity of the formulation to produce strong immunological response and/or defense. BACKGROUND AND PRIOR ART

Capsicum is a genus of plants from the nightshade family Solanaceae, native to Mexico, and now cultivated worldwide. Some of the members of Capsicum are used as spices, vegetables and medicines. Capsaicinoids are alkaloids produced as a secondary metabolite by chili peppers (capsicum), probably as deterrents against herbivores. Capsaicinoids found in capsicum are Capsaicin, dihydrocapsaicin , nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin and the like. Capsicum, is commonly used in food products to give them added spice or "heat" (piquancy) because of the burning sensation caused by capsaicinoids when it comes in contact with human flesh. The degree of heat found within a food is measured on the Scoville scale.

Typically, capsaicin and dihydrocapsaicin account for 60 to 75% and 20 to 25% of the total capsaicinoids mixture present in seeds and fleshy fruits of plants of genus Capsicum. These two compounds are twice as potent as other capsaicinoids.

Pure capsaicin is a hydrophobic, colorless, odorless and crystalline to waxy compound. Capsaicin can be readily obtained by ethanol extraction of the fruit of capsicum frutescens or capsicum annum. It is known by the chemical name N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-trans-6- enamide with molecular formula CIgH27NO3 It is practically insoluble in cold water, but freely soluble in alcohol, ether, benzene and chloroform. Alcoholic beverages also dissolve capsaicin due to the solvent characteristics of ethanol. Capsaicin is a nonpolar molecule, and is therefore hydrophobic. The lipophilic capsaicin is able to mix freely with the fats and oils.

Dihydrocapsaicin is an analog and congener of capsaicin in chili peppers (Capsicum). lit is known by the chemical name 8-methyl-N- vanillylnonamidenon with molecular formula C18H29NO3 Like capsaicin it is an irritant and has about the same pungency as capsaicin. Pure dihydrocapsaicin is a lipophilic, colorless, odorless crystalline to waxy compound.

Capsaicin is currently used in therapeutics, in topical ointments to relieve the pain of peripheral neuropathy such as post-herpetic neuralgia caused by shingles. Therapeutically capsaicin has been used as a topical analgesic, explored as a cure for diabetes and is also able to kill prostate cancer cells by causing them to undergo apoptosis. Tumors formed by human prostate were treated with capsaicin and the tumours were found to about one-fifth the size of untreated tumors. Capsaicin is able to trigger apopotosis in human lung cancer cells as well. It is also used in certain medical studies as a measure of a persons tolerability to pain before that person is tested with a new drug, for example a painkiller. Capsaicin may also be used as a cream for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains and sprains. Pain is initiated when the peripheral terminals of a particular group of sensory neurons, called nociceptors, are activated by noxious chemical, mechanical, or thermal stimuli. These neurons, whose cell bodies are located in various sensory ganglia, transmit information regarding tissue damage to pain processing centers in the spinal cord and brain (Fields Pain (McGraw-Hill, New York, 1987).

Capsaicin has long been used as an experimental tool because of its selective action on small diameter afferent nerve fibers C- fibers and A- delta fibers that are believed to signal pain. In animals, capsaicin appears to trigger C- fiber membrane depolarization by opening cation channels permeable to calcium and sodium. Capsaicin, works to relieve pain by causing a localized degradation of the C neuron endings, and it is the only analgesic known to relieve pain by this mechanism.

The receptor for capsaicin is called the vanilloid receptor subtype 1 (VRl) because capsaicin is chemically defined as part of the vanilloid group. VRl is a cation channel that can also be activated by noxious heat (thermal stimuli) or mechanical stimuli, in addition to its chemical activation of capsaicin. The activity of capsaicin results from its binding to, and activating, an ion channel called vanilloid receptor 1, or VRl. Under normal circumstances, when the VRl ion channel is activated it opens for a short time, causing the C neurons to transmit a pain signal toward the brain. When capsaicin binds to, and activates VRl, it causes a series of events within the cell that degrade the pain-sensing endings, or terminals of the C neuron, thereby preventing the neuron from transmitting pain signals.

The effects of capsaicin are confined exclusively to the region of application because of low distribution to other areas of the body after capsaicin is administered locally. For example, after injection into a joint space or after application in a surgical procedure to the cut surfaces of skin, muscle and bone, capsaicin enters the blood slowly by diffusion from its site of initial application. Thereafter, capsaicin is highly metabolized, or broken down, by the liver into various inactive compounds, none of which retain any of the analgesic properties of capsaicin. As a consequence, capsaicin does not usually act at sites in the body distant from its initial application, nor is the body exposed to any derivatives of capsaicin that could act in a similar manner.

By contrast, opioids and many other analgesics like NSAID( nonsteroidal anti inflammatory drugs) must be given orally or parenterally, thereby subjecting the patient to circulation of high concentrations of the drug. These high circulating concentrations may exert undesirable side effects by acting on parts of the body unrelated to pain perception. For example, opioids may cause constipation when used for long periods of time. Opioids also may cause alteration of mood and alertness, and can cause patients to feel drowsy, euphoric or sleepy. NSAID cause gastric irritation and burning in the epigastrium. US patent application No. 20030157185 discloses a topical treatment for treatment of neuropathy, provided with a method of treating the symptoms of diseases related to restricted blood flow and nerve impairment by the topical application of a composition containing vasodilators, stimulants of the lymphatic system, mobilizer of white blood cell activity and a pain relieving amount of capsaicin. The treatment is particularly useful for patients suffering from fibromyalgia, diabetic neuropathy, and toxic neuropathy

US patent No. 5885597 discloses a pain relieving topical composition, consisting of an effective amount of a combination of at least one corticoid analgesic, at least one arylpropionic acid type analgesic, and at least one p-aminobenzoic acid ester type local anesthetic; in amount effective in enhancing the effectiveness in relieving pain of the combination of capsaicin, and an amount effective to increase the transmission thereof of through the skin of at least one phospholipid and at least one poly oxy ethylenepolyoxypropylene copolymer.

Patent application No. WO2004056305 discloses a method for providing pain relief in humans and animals by administering an injectable or implantable dose of capsaicin or capsaicin analogue to a site for the treatment of acute or chronic pain, nociceptive and neuropathic pain, pre-and post-operative pain, cancer pain, pain associated with neurotransmitter dysregulation syndromes and orthopedic disorders. Patent application No.WO0168082 discloses method and use of capsaicin or its analogs and an anesthetic for the treatment or prevention of ocular pain or inflammatory reaction in eye. The method involves administering a therapeutically effective amount of capsaicin in the eye or an analogue or a mixture thereof, wherein prior to the administration eye is pretreated with a therapeutically effective amount of at least one anaesthetic.

In all these formulations, capsaicin or its analogs are used locally thereby providing only temporary and symptomatic relief at the site of injection/infiltration or topical application of the dose. In the abovesaid applications capsaicin or its analogs are mainly in combinations with other drugs such as steroids, which increases side effects due to systemic absorption of the drug.

Hence there is a need for a novel capsaicin formulation which can be administered orally, which has a curative effect rather than a symptomatic effect and has a longer effect.

OBJECTS OF THE INVENTION

One of the objects of the invention is to provide a novel formulation of capsaicinoids to relieve various pains.

Another objective is to provide a novel formulation of capsaicinoids which can be orally administered. Yet another objective is to provide a novel formulation of capsaicinoids which has a curative effect rather than a symptomatic.

Yet another objective is to provide a novel formulation of capsaicinoids which has better therapeutic efficacy.

Yet another objective is to provide a novel formulation of capsaicinoids which requires low dose.

Yet another objective is to provide a novel formulation of capsaicinoids which has minimum side effects.

Yet another objective is to provide a novel formulation which is easy to manufacture.

SUMMARY OF THE INVENTION

According to this invention there is provided a formulation comprising a potentized mixture of an extract of capsaicin and an extract of dihydrocapsaicin in a ratio of about 50 : 1 to about 1 : 50 [nohereinafter called capsaicin analog] in a solvent where the ratio of capsaicin analog to solvent ranges from about 0.5 to 100 to about 2 :100.

Typically, the solvent is at least one solvent selected from a group of solvents consisting of benzene, alcohol, chloroform, diethyl ether and water. Preferably, the solvent is distilled water.

Typically, the potency of the formulation is Ic to 5 million c.

Typically, the extract of capsaicin is an alcoholic extract.

Typically, the extract of dihydrocapsaicin is an alcoholic extract

According to this invention there is also provided a process for the preparation of the formulation comprising the following steps:

(i) mixing of an aqueous extract of about 0.75 to 1.25 milligram capsaicin and 0.75 to 1.25 milligram of dihydrocapsaicin with 90 to 100 milliliters of a solvent in suitably sized vial; (ii) homogenizing the mixture by shaking the mixture of step (i) thoroughly ; (iii) administering 12 - 20 powerful strokes to the mixture of step (ii) to obtain a potentized mixture of potency

Ic; (iv) mixing of about 0.75 to 1.25 milliliter of potentized mixture of potency Ic of step (iii) with about 90 to

100 milliliter of solvent in another vial; (v) homogenizing the mixture by shaking the mixture (iv) thoroughly; (vi) administering 12 - 20 powerful strokes to the mixture of step (v) to obtain a potentized mixture of potency 2c;

(vii) repeating the steps (iv) to step (vi) to obtain different potency capsaicin medicines in the range of 30 to 5 million c.

Typically, the proportion of capsaicin to solvent is between 1 :99 to 50:50.

Typically, the shaking is carried out either manually or by a suitable mechanical device.

Typically, the stroking is carried out either manually or by a suitable mechanical device.

DETAILED DESCRIPTION OF THE INVENTION

Detailed description of the ingredients:

The botanical references of the fruit used for formulation is as follows:

Botanical name \Capsicun annum

Sanskrit name :Katuvira

Common names xayenne, chili, chile, chillies, chili pepper, red pepper, red chilli, tabasco pepper, African pepper, bird pepper. Habitat xapsicum is native to Mexico and now cultivated worldwide,

Parts Used -.fruit. Constituents : the pungent constituents found in capsicum are the capsaicinoids. The major capsaicinoid are capsaicin 48.6%, dihydrocapsaicin 36%, nordihydrocapsaicin 7.4%,homodihydrocapsaicin 2%, and homocapsaicin 2%, ( approximate percentages) . Capsicum also contains ascorbic acid, red carotenoids, thiamine, proteins and fixed oils.

Action xarminative, digestive irritant, stomachic, stimulant, rubefacient, analgesic, antispasmodic, astringent, hemostatic and emetic.

In accordance with the present invention there is provided a formulation comprising a potentized mixture of an extract of capsaicin and an extract of dihydrocapsaicin in a ratio of about 50: 1 to about 1: 50 [nohereinafter called capsaicin analog] in a solvent where the ratio of capsaicin analog to solvent ranges from about 0.5 to 100 to about 2: 100.

In accordance with the present invention there is also provided a method for the preparation of an analgesic comprising Capsaicin alkaloid and Dihydrocapsaicin. Typically, one milligram of the Capsaicin alkaloid extracted in ethanol and one milligram of Dihydrocapsaicin also extracted in ethanol are mixed with about 99 ml of distilled water (or alcohol) in an one dram size vial. The resultant mixture was thoroughly shaken and 15 powerful strokes administered with a mechanical device. This mixture is labeled as Capsaicin analogs Ic (Ic potency)

In the next step ImI (or such small part) of Capsaicin analogs Ic is mixed with 99 parts (or such high proportion) in another vial to undergo potentization with about 15 mechanical strokes to arrive at Capsaicin analogs of 2c potency. Likewise, the procedure is repeated to reach to 3c, 4c....30c..50c,..100 c, 1000c, 50000c, up to 5 million c potencies. This mechanical process of serial dilution and shaking is called potentization in homeopathy.

This new preparation uses a combination of Capsaicin and Dihydrocapsaicin, which are separated with a special method and measured by procedure called high performance liquid chromatography (HPLC). They are specific alkaloids which are well defined substance as compared to the earlier homoeopathic preparation from '20 grains of powdered pods'. The preparation in accordance with this invention is prepared by a process called potentization, whereby series of dilutions are carried out with a device, leading to an infinitesimal dose form which hardly contains any measurable molecule of the original capsaicin alkaloid any longer. The medicine prepared in accordance with this invention has been found to provide remarkable results in the treatment of various conditions including Cancer pain, pain in Osteoarthritis and rheumatoid arthritis, acute or chronic gastritis, pain of Cervical Spondylitis, pain as a result of Mastitis, bronchitis, Peptic Ulcers, Trigeminal Neuralgia, any deep rooted pain such as pain arising from Calcaneal Spur or Prolapsed Intervertebral Disc or Ankylosing Spondylitis, in the treatment of Peripheral Neuropathy or pain due to Oral Lichen Planus.

EXAMPLES:

Provided herein below are some cases studies involving the use of Capsaicin analogs in accordance with this invention: Case 1 : Cancer pain

A 65 years old female presented with multiple cancer growth affecting bones and lungs. There was constant burning pain in the hip, back and all bones as well as several joints. The pain did not allow her to have peaceful sleep. She was treated with conventional analgesics for the pains without any relief including capsaicin plain medicines. Then she was prescribed Capsaicin analogs 17c, four times a day for two weeks. She started getting relief in pain within two days, and achieved pain relief by over 70% in two weeks time. The treatment was continued for about six months in subsequent higher potencies for long term relief. Case 2: Osteoarthritis

A 68 year old female, a known case of Osteoarthritis of both knees, was under medical care since over one year. She had received conventional homeopathic medicine of plain capsaicin with little relief. The pain in the knees was worse on movement, climbing and at night. She was prescribed Capsaicin analogs 17c, three times a day for three weeks. Her pain was relieved by over 60%. The medicine was continued in subsequent higher potencies for four months to achieve 80 to 90% pain relief.

Case 3: Acute gastritis

A 28 years old lady, presented with complain of burning in epigastric region after food, for last six months. She was almost addicted to the conventional antacids. She was prescribed Capsaicin analogs 17c, thrice a day for two weeks and her burning pain reduced by 50%. Then her intake of conventional antacids was reduced and she was prescribed Capsaicin analogs 30c, thrice a day for a month. Her symptom was reduced to only occasional burning. The conventional antacid administration was completely stopped. After two more weeks of therapy of Capsaicin analog 30c she was totally symptom free.

Case 4: Osteoarthritis

A 75 years male, presented with pain in various joints with osteoarthritis changes and osteoporosis. He also has severe gastritis and was not able to tolerate conventional pain killers as they aggravated the symptoms of gastritis. He was first given plain capsaicin prescribed Capsaicin analogs 17c for a month, then 30c for another month and then 50c. His pain as well as gastritis improved by over 90%.

Case 5: Cervical Spondylitis

A 56 years old male, presented with severe Cervical Spondylitis, since five years. He complained of pain in the neck, extending to the right side up to his little finger; with restricted neck mobility. He was prescribed Capsaicin analogs 30c, thrice a day for seven days. His pain reduced by 50%. The medicine was continued in 50c potency for a month. His pain reduced further and neck movements improved remarkably.

Case 6: Acute Gastritis

A 25 years male, presented with Acute Gastritis, upper abdominal pain since three weeks. He was prescribed Capsaicin analogs -17c, four times a day for a five day period. His pain disappeared.

Case 7: Chronic Gastritis

A 50 years old male patient, presented with Chronic Gastritis since six months. He was prescribed Capsaicin analogs 17c, three times a day for two weeks. He improved by 70%, the medicine was continued for a month. He was free from symptoms thereafter.

Case 8: Rheumatoid Arthritis,

A case of Rheumatoid Arthritis, presented with severe acute pain in multiple joints, with swelling. He was prescribed Capsaicin analogs 17c, every two hours for two days. His pain reduced by over 70%, Case 9: Mastitis

A case with pain in breasts since a month, resulting from physical trauma was prescribed Capsaicin analogs 17c, thrice a day for two weeks. Her pain almost disappeared.

Case 10: Acute bronchitis

A case presented with acute bronchitis, was coughing with pain in the chest, expectoration and body ache. She was prescribed Capsaicin analogs 17c, four times a day for five days. Her cough improved to almost zero and her sense of well being improved.

Case 11: Peptic Ulcer

A 45 years old male, presented with chronic gastritis with peptic ulcer since five years. He was on daily habitual dose of antiulcer medication for last two years. He was prescribed Capsaicin analogs 17c, and then 30c, thrice a day for a month. He felt better and his dose of conventional antacids was reduced. He was then prescribed Capsaicin analogs 100c and within four weeks, he could stop all his conventional medicines for peptic ulcer. He was kept on Capsaicin analogs 200c, for two more months. He was completely free from the disease and then the treatment was terminated.

Case 12: Trigeminal Neuralgia

A 75 years old female, presented with exacerbation of Trigeminal

Neuralgia. She was on high dose of carbamezapine. She was prescribed Capsaicin analogs 30c, four times a day for about five days. Her neuralgia was better within a day and reduced to over 90% in five days.

Case 13:

A 56 years old female, presented with Calcaneal Spur, pain in the heels for over three months. She was prescribed Capsaicin analogs 30c, thrice a day for a week. The pain was better by 50%. The medicine was given in 100c potency and she improved 80%.

Case 14: Prolapsed Intervertebral Disc

A 46 years old female presented with Prolapsed Intervertebral Disc between L5-S1. The pain in the lower lumbosacral was severe and extending downwards, with peripheral numbness. Patient had restricted mobility. She was prescribed Capsaicin analogs 30c, to be taken every two hours. Her pain reduced within about 12 hours to 50%. The medicine was continued in 50c potency and within three days of medication, rest and exercise she was remarkably better.

Case 15: Ankylosing Spondylitis

A 29 years old female, was under medical care for Ankylosing Spondylitis. Her pain in the back was not responding to conventional homeopathic treatment. She was prescribed Capsaicin analogs 30c, thrice a day for a week. The pain reduced drastically. The medicine was continued for a month in 100c potency to achieve over 80% improvement in pain. Case 16: Peripheral Neuropathy

A 60 years old female with diabetes, presented with burning palms and sole, pricking and tingling numbness of the feet and hands. She was prescribed Capsaicin analogs 30c, thrice a day for three weeks. She was better by 70% in all her symptoms.

Case 17: Pain in Oral Lichen Planus

A case presented with oral Lichen Planus. She was prescribed conventional homeopathic medicine. Her lesions were reduced but her burning pain in the mouth was not reduced. She was prescribed Capsaicin analogs 30c, three times a day for three weeks. Her pain completely disappeared.

While considerable emphasis has been placed herein on the specific structure of the preferred embodiment, it will be appreciated that many alterations can be made and that many modifications can be made in the preferred embodiment without departing from the principles of the invention. These and other changes in the preferred embodiment as well as other embodiments of the invention will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation

Claims

Claims:
1. A formulation comprising a potentized mixture of an extract of capsaicin and an extract of dihydrocapsaicin in a ratio of about 50 : 1 to about 1 : 50 in a solvent where the ratio of combined extract to solvent ranges from about 0.5 to 100 to about 2 :100 .
2. A formulation as claimed in claim 1, wherein the solvent is at least one solvent selected from a group of solvent consisting of benzene, alcohol, chloroform, diethyl ether and water.
3. A formulation as claimed in claim 1, wherein the solvent is water.
4. A formulation as claimed in claim 1, wherein the potency of the formulation is Ic to 5 million c.
5. A formulation as claimed in claim 1, wherein the extract of capsaicin is an alcoholic extract.
6. A formulation as claimed in claim 1, wherein the extract of dihydrocapsaicin is an alcoholic extract.
7. A process for the preparation of the formulation as claimed in claim 1 , comprising the following steps :
(i) mixing of aqueous extract of 0.75 to 1.25 milligram capsaicin and 0.75 to 1.25 milligram of dihydrocapsaicin with 90 to 100 milliliters of a solvent in a suitably sized vial; (ii) homogenizing the mixture by shaking the mixture of step (i) thoroughly ; (iii) administering 12 - 20 powerful strokes to the mixture of step (ii) to obtain a potentized mixture of potency
Ic; (iv) mixing of about 0.75 to 1.25 milliliter of potentized mixture of potency Ic of step (iii) with about 90 to
100 milliliter of solvent in another suitably sized vial; (v) homogenizing the mixture by shaking the mixture (iv) thoroughly; (vi) administering 12 - 20 powerful strokes to the mixture of step (v) to obtain a potentized mixture of potency
2c; (vii) repeating the steps (iv) to step (vi) to obtain different potency valued capsaicin analog in the range up to atleast 5 million c.
8. A process for the preparation of the potentized formulation as claimed in claim 7, wherein the proportion of homogeneous mixture of capsaicin and dihydrocapsacin to solvent is between 1 :99 to 50:50.
. A process for the preparation of the potentized formulation as claimed in claim 7, wherein the shaking is carried out either manually or by a suitable mechanical device.
10. A process for the preparation of the potentized formulation as claimed in claim 7, wherein the stroking is carried out either manually or by a suitable mechanical device.
PCT/IN2007/000253 2007-05-03 2007-06-22 Oral medicinal preparations WO2008136012A1 (en)

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IN855MU2007 2007-05-03

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140171511A1 (en) * 2011-07-07 2014-06-19 Eva Millqvist Cough Reducing Product

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050020690A1 (en) * 2002-12-18 2005-01-27 Algorx Infiltration of capsaicin into surgical sites and open wounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050020690A1 (en) * 2002-12-18 2005-01-27 Algorx Infiltration of capsaicin into surgical sites and open wounds
US20060269628A1 (en) * 2002-12-18 2006-11-30 Algorx Infiltration of capsaicin into surgical sites and open wounds

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140171511A1 (en) * 2011-07-07 2014-06-19 Eva Millqvist Cough Reducing Product

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