KR20080108994A - Composition for treating bacterial, viral, fungal diseases, inflammation and pain - Google Patents

Abstract

The present invention is directed to compositions and methods of treating bacterial, viral, fungal diseases; inflammation or inflammatory-related disorders; pain; and skin conditions. The composition comprises an organic solvent extract, which is prepared by the method comprising the steps of: (a) mixing methionine with water, (b) adding an aqueous hypochlorite solution to the methionine solution and mixing, (c) adding a water-immiscible organic solvent to (b) and mixing, and (d) separating the organic solvent phase from the water phase to obtain the organic solvent extract. ® KIPO & WIPO 2009

Description

Composition for the treatment of bacterial, viral, fungal diseases, inflammation and pain {COMPOSITION FOR TREATING BACTERIAL, VIRAL, FUNGAL DISEASES, INFLAMMATION AND PAIN}

The present invention is a bacterial, viral, fungal disease; Inflammation or inflammation-related disorders; ache; And compositions and methods for treating skin conditions. The composition is prepared by organic solvent extraction of the reaction product of methionine and hypochlorite.

The human body is vulnerable to many different forms of infection of various sources. Virus infections, usually in the form of a common cold, affect nearly every year. Coughing and sneezing associated with a cold may simply be annoying, but other common viral infections can be much more serious. Influenza, for example, is the leading cause of hospitalization and death among Americans, with an average of 36,000 deaths and 114,000 inpatients per year.

Bacterial infections can be dangerous as well. Staphylococcal infections caused by Staphylococcus family and bacteria are the cause of many serious postoperative complications. Staphylococcal infections are also a major cause of food poisoning cases, including toxic shock syndrome (Toxic Shock Syndrome (TSS)), pneumonia, bone infections (osteomyelitis), lactation mastitis, endocarditis (internal heart infection), and bacteremia (blood infections) and It may be the cause for the same life-threatening conditions. Other healthy people typically do not get seriously ill from staphylococcal infections, but are immune, including elderly people, newborns, and people with chronic diseases such as diabetes, cancer, lung disease, kidney disease, or HTV / AIDS. Weakened individuals are particularly at risk.

Individuals with weakened immune systems are also at risk from fungal infections. Fungal infections cause conditions in the form of sinus infections, athlete's foot, and yeast infections in millions of people.

As used herein, the general term “pain” refers to all categories of pain as follows: traumatic pain due to injury, postoperative pain, inflammatory pain; Pain associated with diseases such as cancer, AIDS, arthritis, herpes, migraine; Pain associated with neuropathy such as diabetic neuropathy, burning pain, brachial plexus extraction, laryngeal neuralgia, fibromyalgia, gout, and other forms of neuralgia, neuropathic and idiopathic pain syndromes; Pain of varying severity, that is, mild, moderate and severe pain; Acute and chronic pain; And certain organ pains such as eye and corneal pain, bone pain, heart pain, skin / burn pain, visceral (kidney, gallbladder, etc.) pain, arthralgia, toothache and muscle pain.

Connective tissues suffer from constantly shinning stresses and injuries. Acute or chronic shocks and naturally occurring degenerative diseases all cause painful inflammation in the joints of the neck, back, arms, buttocks, ankles and feet. This pain is common and often incapacitating.

Current pain therapies include the use of opioid narcotic analgesics such as morphine and fentanyl, nonsteroidal anti-inflammatory agents (NSAIDS) such as aspirin, ibuprofen and cyclooxygenase inhibitors, or ion channel blockers such as lidocaine and novacaine do. These therapies all have limitations, for example, they cause resistance, dependence, constipation, respiratory depression and sedation (opium). NSAIDS have gastrointestinal side effects, increase bleeding time, and are not effective in treating severe pain.

Inflammation is a local reaction of living tissue due to injury that can be caused by various endogenous and exogenous factors. Exogenous factors include physical, chemical and biological factors. Endogenous factors include inflammatory mediators, antigens, and antibodies. Endogenous factors often develop under the influence of exogenous damage. Inflammatory responses are often followed by alterations in the structure and permeability of the cell membrane. At the tissue and organ level, inflammation is labeled with pain, edema, reddening, temperature rise, and in some cases loss of function.

Inflammation is affected by various exogenous and endogenous agents. Endogenous factors, ie mediators, antigens, and autogens, determine the nature and type of inflammatory response, especially its transition in the injury zone. When tissue damage is limited to the production of mediators, an acute form of inflammation develops. If an immune response is also involved in the process, long-term inflammatory processes will develop through the interaction of antigens, antibodies, and autoantigens. Various exogenous agents, such as infections, injuries, radiation, and also damage the cell membranes that initiate biochemical reactions, provide the direction of molecular level inflammatory processes.

Nonsteroidal anti-inflammatory agents (NSAIDS), such as aspirin, can block certain linkages of the inflammatory process, but these agents cannot stabilize the damaged cell membranes, making the effects of the agent on the inflammatory process limited and insufficient.

Bacterial, viral, fungal diseases; Inflammation or inflammation-related disorders; ache; And compositions and methods for the treatment of skin conditions are desired. The composition must be easy to manufacture and economical, the method must be effective and free of significant side effects.

Summary of the Invention

The present invention relates to an organic solvent extract prepared by the reaction of an aqueous methionine solution with an aqueous hypochlorite solution and extraction of the reactive product using a water-immiscible organic solvent such as mineral oil. The reactive product is stable for at least several months at room temperature in a water-immiscible organic solvent.

The invention also relates to bacterial, viral, fungal diseases; Inflammation or inflammation-related disorders; ache; Or to a method of treating a skin condition. The method comprises administering a composition containing an organic solvent extract prepared according to the invention to a subject in need thereof. The composition can be applied in any acceptable systemic dosage form, including topical, oral and parenteral (eg, intravenous, intramuscular, subcutaneous or rectal). Topical administration and oral administration are preferred.

Detailed description of the invention

The present invention describes organic solvent extracts useful for treating various diseases or disorders. The organic solvent extract is prepared by a process comprising the following steps: (a) mixing methionine with water, (b) adding an aqueous hypochlorite solution to the methionine solution and mixing at a temperature between 0 ° C. and ambient temperature Step (c) adding a water-immiscible organic solvent to (b) and mixing, and (d) separating the organic solvent phase from an aqueous phase to obtain an organic solvent extract.

The organic solvent extract is prepared by first preparing a reactive product, and then stabilizing the product by extracting the reactive product into a water-immiscible organic solvent.

The reactive product is prepared by first mixing methionine with water to form a suspension. Methionine can be L-methionine, D-methionine, or mixtures thereof. The mixing is preferably carried out under an inert gas such as argon. Mixing times are typically from a few seconds to several minutes. The mixing can be carried out by any mixing means, for example by a blender.

An aqueous solution of hypochlorite, such as sodium hypochlorite, is added to the methionine solution and mixed thoroughly. The reaction mixture is then left until it is clear, and excess methionine forms a foam at the top. Optionally the foam is removed. The reaction is carried out at a temperature between 0 ° C. and ambient temperature, preferably at a low temperature such as 0-5 ° C. The reaction is preferably carried out under an inert gas such as argon.

The reactive product is not stable in water and is extracted with a water-immiscible organic solvent. Water-immiscible organic solvents useful in the present invention are preferably semi-polar or nonpolar solvents having a polarity of about 0.1-7.5, such as mineral oil, hexane, heptane, methylene chloride, vegetable oil, or ethyl acetate to be. More preferred are nonpolar solvents. The extraction is carried out immediately after the methionine / hypochlorite reaction, preferably within 5 minutes, preferably within 2 minutes, more preferably within 1 minute.

The water-organic solvent mixture is allowed to stand. The organic phase is separated from the aqueous phase by any method known to those skilled in the art, such as pouring or pipetting, to obtain an organic solvent extract. Optionally any insoluble residues in the organic solvent extract are removed by filtration, decantation, centrifugation, or any method known to those skilled in the art. The reactive product is stable in the organic solvent at room temperature (22-28 ° C.) for at least 1 month, preferably 3 months, more preferably 6 months or 1 year.

In a typical reaction, 700-800 ml of distilled water, 20-100 g of methionine, and 300-500 ml of 3-12% hypochlorite are used. In a typical extraction, about 200-300 ml or more water-immiscible organic solvents are used. The amount of the reagents may increase or decrease depending on the ratio.

The organic solvent extract of the present invention is useful for the treatment of various diseases or disorders. The organic solvent extract may be used as it is or may be administered in the form of a pharmaceutical composition additionally containing a pharmaceutically acceptable carrier. In one embodiment, the organic solvent extract can be incorporated into any acceptable carrier including creams, gels, lotions or other types of suspensions which can stabilize the active ingredient and deliver it to the affected area by topical application. . In another embodiment, the pharmaceutical composition may be in dosage form such as tablets, capsules, granules, granules, powders, syrups, suppositories, injections and the like. The pharmaceutical composition may be prepared by conventional methods.

In one embodiment, the invention provides a method of treating a bacterial disease, such as staphylococcal infection.

In another embodiment, the present invention provides a method of treating a viral disease, such as influenza infection.

In another embodiment, the present invention provides a method for treating fungal diseases such as athlete's foot, yeast infection, and sinus infection due to fungal infection.

In another embodiment, the present invention provides a method of treating a skin condition such as skin damage, skin spots, or warts caused by burns or sun.

In another embodiment, the present invention provides a method of treating an inflammation or inflammation-related disorder. The present invention alleviates symptoms associated with inflammation or inflammation-related disorders such as pain, edema, redness, temperature rise, or in some cases loss of function.

In another embodiment, the present invention provides a method for alleviating symptoms of pain regardless of their cause. "Pain" as general terms treatable by the methods of the present invention include traumatic pain, neuropathic pain, organ pain, and disease related pain. Traumatic pain includes pain due to injury, postoperative pain and inflammatory pain. Neuropathic pain includes neuropathic and idiopathic pain syndromes and pain associated with neuropathy such as diabetic neuropathy, burning pain, brachial plexus extraction, laryngeal neuralgia, fibromyalgia, gout, and other forms of neuralgia. Organ pain includes eye, cornea, bone, heart, skin / burn, visceral (kidney, gallbladder, etc.), joint, tooth, and muscle pain. Disease-related pain includes pain associated with cancer, AIDS, arthritis, herpes and migraine headaches. The present invention relates to pain of varying severity, i.e. mild, moderate and severe pain; Reduces acute and chronic pain. For example, the present invention is effective in treating pain, arthralgia, myalgia, tendon pain, and burn pain resulting from inflammatory arthritis or degenerative arthritis.

The method of the present invention comprises administering a composition containing an organic solvent extract prepared according to the present invention to a subject in need thereof. The compositions of the present invention are applicable in any acceptable systemic dosage form, including topical, oral, parenteral (eg, intravenous, intramuscular, subcutaneous or rectal), and other systemic routes of administration. Dosing of the composition may vary based on the extent of injury and the individual response of each patient. Topical administration and oral administration are preferred.

For topical application, it is preferred to apply the composition on the affected area and then rub it into it. The composition can be applied 1-5 times a day, preferably 1-3 times a day, and preferably 3 times a day. The active compound passes through the skin to the unpleasant site. Those skilled in the art will appreciate that a wide variety of delivery mechanisms besides topical application, such as ingestible tablets, ingestible liquids, inhalers and aerosols, are also suitable.

The following examples further illustrate the invention. These examples are merely intended to illustrate the present invention and should not be construed as limiting.

Example  1. Manufacture of products

In the blender, 720-750 ml of distilled water at 0-4 ° C. and 20 g DL methionine fine powder (Degussa Corp., Richfield Park, NJ) were combined and mixed for several seconds under argon. After the methionine solid was uniformly suspended in distilled water, 370-400 ml of 0-4 ° C. Clorox bleach (6% sodium hypochlorite) were added and mixed under argon at blend speed for 30 seconds. The reaction was allowed to rest for 30 seconds to 1 minute until the solution became clear and a foam formed on top. The foam was excess methionine and was optionally removed.

The solution was immediately poured into (<2 minutes) extraction blender and 240 ml of mineral oil (STO Oil Corp., San Marcos, TX) at room temperature were added and then blended at low speed for 20 seconds under argon.

The water-oil mixture was allowed to stand for 3-4 hours, after which the oil phase was removed and filtered through 20-micron filter paper. The filtrate was stored in an open container for 3 days to allow argon to dissipate, so that the oil filtrate was ready for use as a product.

Example  2. Hepatotoxicity  exam

Rat populations were subjected to an in vivo assessment of the hepatotoxicity of the product of Example 1.

10 rat controls were untreated for histology and control analysis of basal serum enzymes.

In group 2 of 10 rats, standard saline was gavaged twice daily to determine the effect of repeated treatment and gavage on the liver.

Only the mineral oil was gavaged twice daily for the third group of 25 rats.

For the fourth group of 25 rats, the product of Example 1 was gavaged twice daily.

After 28 days, rats were anesthetized and liver tested according to standard methodology. It was concluded that the consumption of the product of Example 1 showed no signs of hepatotoxicity.

Example  3. Treatment of infection

The product of Example 1 was used to treat subjects who exhibited various infections. The results are summarized in Table 1.

object Condition Application method apply result Target 1 Staphylococcus Infection on Leg Topical 3 months Symptom relief Target 2 Sinus conditions Topical 1 week Symptom relief

Example  4. Treatment of joint pain and muscle pain

Subjects with arthralgia, insect bite pain, or burn pain were treated with the product of Example 1. The results are summarized in Table 2.

object Condition Application method Relaxation time Target 1 Hip pain Topical Immediately Target 3 Arthritis pain Topical Immediately Target 4 Back / knee pain Topical Immediately Target 5 Knee pain Topical Immediately Destination 6 Back / knee pain Topical Immediately Target 7 Buttock pain Topical Immediately Target 8 Arthritis pain Topical Immediately Target 2 Hand burn pain Topical Immediately Target 1 Insect bite pain Topical Immediately

Table 2 shows that pain was immediately relieved when topically applied the product to subjects with various pains.

Example  5. Treatment of wounds or injuries

The product of Example 1 was applied topically three times a day to people with burns or skin conditions as shown in Table 3. After application of the product, the symptoms of the subjects were alleviated.

object Condition Application method Application time Target 1 burn Topical 3 days Target 9 Sun spots on the face Topical 3 months Target 10 Purple sunburn Topical 3 days Destination 11 Sun damage Topical 2 months Destination 12 Sun damage Topical 2 months Destination 13 Bleeding facial skin Topical 2 weeks Target 2 mantis Topical 3 weeks Destination 14 Diabetic Ulcers of the Legs and Feet Topical 1 week

The present invention, and methods and methods of making and using the same, are now described in complete, clear, concise and accurate terms, such that any person skilled in the art can make and use the same. What has been described above is a description of preferred embodiments of the invention and modifications may be made therein without departing from the scope of the invention as disclosed in the claims. In order to particularly point out and explicitly claim the subject matter regarded as the present invention, the present specification ends with the following claims.

Claims (12)

Organic solvent extract prepared by the method comprising the following steps: (a) mixing methionine with water, (b) adding an aqueous hypochlorite solution to (a) and mixing at a temperature between 0 ° C. and ambient temperature, (c) adding a water-immiscible organic solvent to (b) and mixing, and (d) separating the organic solvent phase. The organic solvent extract of claim 1, wherein the water-immiscible organic solvent is hexane, heptane, methylene chloride, mineral oil, vegetable oil, or ethyl acetate. The organic solvent extract of claim 2, wherein the water-immiscible organic solvent is mineral oil or hexane. The organic solvent extract of claim 1, wherein steps (a) and (b) are carried out under an inert gas. The organic solvent extract of claim 1, wherein the methionine is D-methionine, L-methionine, or a mixture thereof. A method of treating a bacterial infection in a subject, comprising administering a composition containing the organic solvent extract of claim 1 to a subject suffering from a bacterial infection. A method of treating a viral infection in a subject, comprising administering a composition containing the organic solvent extract of claim 1 to a subject suffering from a viral infection. A method of treating a fungal infection in a subject, comprising administering the composition containing the organic solvent extract of claim 1 to a subject suffering from a fungal infection. A method of treating pain in a subject comprising administering to the subject suffering from pain a composition containing the organic solvent extract of claim 1. The method of claim 9, wherein the pain is joint pain, muscle pain, or burn pain. A method of treating a skin condition in a subject, the method comprising topically administering the composition containing the organic solvent extract of claim 1 to a subject's skin affected area. A method of treating an inflammation or inflammation-related disorder in a subject, comprising administering the composition containing the organic solvent extract of claim 1 to a subject suffering from an inflammation or inflammation-related disorder.