Grouppe Kurosawa: Natural Medicine - Infectious Disease, Traditional Medicines and Microemulsions (print)

Infectious Disease,
Traditional Medicines and Microemulsions

Introduction to the Problem

According to the World Health Organization, the population of the world is increasingly contracting and dying of infectious and somatic diseases, such as HIV, TB, malaria, cancer and heart disease. In 1998, 9,800,000 people died in WHO member states of infectious and parasitic diseases. This figure represents almost half the total overall mortality in developing countries. Most of the infectious disease mortality can be attributed to three diseases—AIDS, TB, and malaria. These diseases cause over 300 million illnesses and 5 million deaths per year. Cancer caused an additional 7,200,000 deaths in 1998. These deaths occur primarily to the poor because they do not have the financial resources to purchase modern drugs.

The alarming increase in the incidence of infectious diseases has become a matter of national and international security. In an age of international air travel, infectious diseases can no longer be quarantined to specific geographical areas. TB is particularly dangerous because one person on average infects between 10 and 15 others every year. Overall, one third of the world’s population is currently infected with the TB bacillus. In 20 years, one billion additional people will become newly infected with TB. Malaria is a serious health problem for 40% of the worlds population. The disease kills 1,000,000 people per year. Mosquito control can drastically curtail the spread of malaria, but no one is going to stop the practice of sex. Sexually transmitted diseases are an increasingly pervasive problem for both developing and developed countries. Programs to encourage the practice of “safe sex” using condoms are having some impact in developing countries, but it is unrealistic to depend on these programs as long term preventative measures. In the United States, the death rate from HIV went down when anti-HIV drugs were introduced into the market. Unfortunately, the infection rate continued to increase. Complacency, epitomized by cries that the “plague was over”, contributed to a newly relaxed attitude toward practicing safe sex. Recently, the rate of new HIV infections in some US cities has reached that of South Africa, a country with one of the highest HIV infection rates in the world. Currently, 36 million people are estimated to be living with HIV. 22 million people have already died from AIDS. Affordable treatments for TB and malaria do exist, but the developing world has largely been denied access to drugs that can treat cancer or HIV infections.

AIDS, TB, and malaria will eventually destroy much of the developing world. In an age when increasing threats of bio-terrorism are commonplace, it is critical that Western governments understand that they cannot ignore the plight of the less fortunate. If the health care dichotomy between Western and developing nations widens much further, the resentment the world’s poor feel toward the more fortunate Western countries could escalate into retaliation. When entire societies are economically collapsing because of the prevalence of infectious disease, it is a natural human emotion to seek a “scape-goat” or to attribute blame to others. If these emotions translate into acts of bio-terrorism, the results would be catastrophic for the world.

Modern pharmaceutical drugs have alleviated a tremendous amount of human suffering. Unfortunately, the drug discovery processes utilized by most Western pharmaceutical companies were not designed to develop inexpensive drugs. The people who often need modern medicines the most are often the very ones who can least afford to purchase them. Many international pharmaceutical companies have been severely criticized for their unwillingness to suspend their international patent rights to allow developing countries to make generic copies of patented medicines for their own internal use. Pharmaceutical companies are in business to make money. If they can do so and still save lives, all to the better. Unfortunately, most large pharmaceutical companies are public companies. They cannot give away their profits in the name of humanity. They can and will be sued by their own investors for fiduciary irresponsibility. This is a difficult concept for many people outside corporate boardrooms to understand. Modern medicines, typified by those developed in a research laboratory, are not going to effectively control most of the diseases affecting the worlds poor. The time frame from discovery to manufacture is too long, and the number of new pathogens previously unidentified grows incrementally every year. Traditional medicines, such as extracts from medicinal plants, have been used for thousands of years to treat a wide diversity of infectious and somatic diseases. They are increasingly seen as viable alternatives to synthetic medicines. Unfortunately, there have been serious limitations to the use of plant extracts as therapeutic agents. Dried herbs and powders are rarely compositionally consistent, and may in fact be toxic if consumed inappropriately. In the last 10 years, there has been a renewed interest in identifying compounds from plants, fungi and bacteria that can be used to treat disease. The National Library of Medicine Database lists thousands of scientific studies that have been conducted on plant and microbial extracts in the hope of finding suitable compounds for treating many of the diseases ravaging the worlds population. Many of these studies have identified very promising therapeutic compounds. However, the identification of promising natural medicinal compounds is only phase one of the problem. The scientists that discovered them cannot turn these compounds into pharmaceutical-grade products. This is the traditional role of the pharmaceutical industry.

Traditional Medicines

Traditional medicinal practitioners in China, Japan, Korea and many other countries have relied for centuries on herbs and medicinal plants as treatments for disease. Although Western medicine has acknowledged that some medicinal plants contain potentially valuable medicines, Western scientists and pharmaceutical companies in particular have largely ignored “traditional” medicines. In some cases, the reasons are nationalistic. Western medicine tends to believe that its science and practices are superior to those practiced in Eastern and developing cultures. In many cases, this is true. Many herbal extracts have minimal effects on the diseases they are purported to treat. Other extracts are toxic and should not be used in large doses. Modern medicine demands proof—not tradition—in evaluating the effectiveness of specific medicines. The two, proof and tradition, are not mutually exclusive.

Most herbal medicines are processed into dried plant leaves, ground powders, and pastes. Very few traditional medicines are used in the form of fresh plant extracts. This is understandable, because fresh, non-dried, plant materials will eventually degrade, or oxidize into products that render the active ingredients useless. Unfortunately, the very process of preparing plant extracts for storage destroys much of their potential utility as medicinal drugs. For example, when plant leaves are dried, the plant cells lose water and collapse. Once plant material is dried, it can never be re-hydrated. Many medicinal molecules are trapped in the dried cellulose mass and cannot be extracted by stomach acid when eaten. Humans do not have the ability to enzymatically degrade cellulose. Many medicinal molecules are actually polar and non-polar lipids. They are not soluble in water, even in the acidified water of the stomach. If they are extracted from plant material by stomach acid, they will largely be degraded by lipases in the intestine. Other molecules, regardless of their solubility, will never be absorbed by intestinal cells because they don’t have the correct molecular structure. Many molecules that do get absorbed are immediately modified by sulphation or other modifications in the intestinal cells and liver and rapidly returned to the lumen of the intestines for destruction by intestinal bacteria. A synthetic or natural drug that has activity in a culture dish may do nothing in the body. Pharmaceutical companies know this problem all too well. Many promising synthetic drugs never make it to market because the stomach or intestines cannot absorb them, they are destroyed by stomach acid, or they are too rapidly cleared from the blood to be effective.

Plant extracts are by definition a composition of many different compounds. Often, the therapeutic utility of a natural herb or plant extract cannot be attributed to a single compound. It is the interaction of different compounds that often makes a plant extract therapeutically useful. The most desirable synthetic drugs are those that are highly specific in their mode of action. For many diseases, this specificity of action is not only desirable, it is necessary. The best example of target specificity are Cox-1 and Cox-2 enzyme inhibitors. Aspirin and other non-steroid anti-inflammatory drugs inhibit both Cox-1 and Cox-2 enzymes. The excessive use of these drugs often results in inflammation of the stomach lining since Cox-1 enzyme products maintain the integrity of the gastric mucosa. Cox-2 enzyme products have recently been linked to rheumatoid arthritis and many different types of cancers. A Cox-2 specific drug was definitely warranted and has recently been developed. Nevertheless, the very power of many natural products is their multiplicity of action, a trait completely antithetical to national drug approval authorities.

Most plant extracts contain both oil and water soluble therapeutic compounds. Many essential oils, the volatile compounds that constitute the fragrance of plants, are very well known to have potent anti-microbial properties. Tea Tree Oil, for example, is a complex blend of volatile compounds that has powerful anti-microbial properties. While many modern antibiotics are highly specific in their properties, anti-microbial essential oils often kill both gram negative and gram positive bacteria, fungi and protozoans will equal ease. During World War II, the production of Tea Tree Oil was so important to the Allied war effort in the South Pacific that the men responsible for extracting and processing the oil were exempt from military service. With the advent of modern antibiotics, the use of products such as Tea Tree Oil as antiseptics stopped. There is a renewed interest in the use of anti-microbial oils now that antibiotic-resistant bacteria are becoming an increasing health problem. While dried plant material is easy to transport and store, it no longer contains essential oils. They are lost during the drying process. The technology described herein was designed to capture both water and oil soluble components from plant extracts without losing them to evaporation or heat denaturation.

The traditional method of purifying plant essential oils involves steam distillation. The plant extract is literally cooked to release the volatile oils, which are subsequently captured in water traps. This extraction process destroys the non-volatile components of the plant extract. Since many plant extracts contain therapeutically useful water and oil soluble compounds, we developed a process of simultaneously extracting oil and water soluble compounds from plant cellulose without heat or denaturation. This process is a trade secret. Once extracted, the normally incompatible water and oil soluble phases can be combined into a therapeutically useful and highly stable microemulsion. Oil soluble components are dissolved into carrier oils that substantially improve their half-lives in the body. Since the liver or kidneys do not rapidly clear micro-droplets of oil, the potency of the dissolved compounds is substantially increased. Water-soluble components can similarly be packaged into nanometer-size liposomes in order to increase their half-life and biological potency. Using the microemulsion technique, water and oil soluble components from different plant extracts can be combined in order to attain a specific therapeutic goal. Microemulsions can be introduced into the body orally, topically to the skin, nasally, as an aerosol for direct entry into the lungs, or via an intravenous “drip”.

The Nature of Emulsions

Emulsions are nothing more than stable suspensions of oil and water based molecules. Milk is an excellent example. It consists of fat globules suspended in water containing freely soluble proteins such as casein and lactalbumin. Most emulsions are unstable, and, like whole milk, will separate into oil and water phases. The microemulsions described herein are extremely stable and will never separate into different phases. Further, and most importantly, the oil and liposome droplets are extremely small—less than 0.2 microns in diameter. This allows the emulsion to be filtered sterilized and injected intravenously into the body. Ordinarily, oils must be sterilized by steam autoclave at 120 degrees Celsius for 20 minutes before they can be injected into the body. The vast majority of therapeutically active ingredients purified from medicinal plants cannot withstand the autoclave sterilization procedure. Non-sterile plant extracts can be orally ingested, but the body often does not absorb the desired therapeutic components. Natural compounds should be formulated so they can be injected or introduced directly into the lungs, as necessary. This requires sterilization. Oils can only be sterilized by heat or by filtration in the form of microemulsions. These oil and liposome droplets are smaller than bacteria and can be freely passaged through large pharmaceutical filters.

Chronic diseases are complex processes that can rarely be controlled by single chemotherapeutic agents. Although oil and water based components could be introduced separately into the body, it would be more effective to introduce them together in the form of a stable microemulsion. The oil and liposome droplets in a miocroemulsion are small enough to traverse the entire capillary network of the body without encountering the risk of blocking blood flow to the tissues. These nano-droplets can penetrate virtually every organ of the body, including lymph nodes and the deep vasculature of solid tumors. They are too large to be removed by the kidneys and too small to fix complement or be readily removed by the liver. They are an ideal delivery vehicle that finally allows Nature’s medicines to be optimally, and economically used in the treatment of infectious and somatic disease.