Medigreen Biotechnology Corporation

Medigreen Biotechnology Corporation has an R&D team that
is skilled in evaluating R&D projects, and in developing and marketing new products efficiently in the shortest time frame. Medigreen Biotechnology Corporation has a group of professional researchers who specialize in immunology, food/health food products, Chinese herbal medicine, in terms of development regulations, pharmaceutical chemistry, and analytical chemistry, and they all have many years of experiences in identifying and analyzing the active components of Chinese herbal medicine and evaluating potential Chinese herbal medicine. Moreover, Medigen Biotechnology Corporation, which is our juridical board, is specialized in the development of new small chemical drugs and has a vast experience in pharmacy.

Their experienced R&D team is a strong backup for us in the development of new products.

I. Introduction

Asthma is a chronic disease worldwide. According to World Health Organization (WHO) statistics, the incidence of asthma is gradually increasing around the world. There are about 100-150 million asthma sufferers at present and the number of sufferers increases by 50% each year. Every year, 180,000 people around the world die from asthma. The prevalence of asthma increases with a modernized society. More highly developed regions have more asthma patients.

For example, the highest prevalence of asthma is in Europe and North Am eric a ; the number of asthma sufferers in these regions is doubling every 10 years. In developed countries, 15% of children and adolescents under the age of 16 require asthma treatment and 20-30% in developing countries.In Taiwan , asthma is one of the ten leading causes of death. Prevalence is as high as 8.5%, so it is currently a disease of high incidence in Taiwan .. The incidence for children aged from 7-12 is as high as 12-13% in Taipei . Presently, one in every three Taiwanese children is allergy-sensitive.

II. The variety of current asthma medications

Most asthma medications in the market contain steroids, hormones or similarly derived compounds, which are highly destructive to the immune system. Long-term use of this kind of medication can lead to even more severe complications, including abnormal growth and tumors. The dosages for inhalation-type drugs are lower, which produces less undesirable side effects, so this type of drug has become the mainstream of asthma treatment. However, since steroids are the major ingredients of inhalation drugs, the presence of side effects still needs to be overcome.

III. Anti-asthma product 1217B: Research Objectives

Anti-asthma product 1217B ingredients include a combination of various plant extracts, which avoids side effects from steroids and hormones. This formula is able to prevent and reduce the onset of asthma and soothe asthma symptoms such as lung inflammation and coughing in the mornings and at nights. In 2005, the preclinical animal model efficacy test, acute toxicity test, 28-day feeding toxicity study, genotoxicity study and CMC (chemical, manufacture and control standards) were completed. The medication received ( FDA IND ) approval from the United States F.D.A. in May 2006, with human clinical trials expected to start between 2006 and 2007 as a step towards the development of new plant-based medications.

In terms of intellectual property, this anti-asthma medication received a patent in the U.S. in 2005; it is expected to receive patents from Europe , China and Taiwan in 2006 and 2007.

To the complete scientific research data, and total patent protection along with the safety, efficacy and unity of the product, are added the enormous advantage that unlike anti-asthma medications currently available in the market, this medication has no side effects. This novel medication will be developed around the world to benefit both asthma-sufferers and the allergy-sensitive.

IV. Anti-asthma medication 1217B: C haracteristics and latest research

(1) Product characteristics

1.	The medication formula combines pure plant extracts, thus avoiding the side effects produced by other anti-asthma medications currently on the market.
ii.	It can prevent and reduce the onset of asthma, soothing asthma symptoms such as lung inflammation and coughing in the mornings and at nights.
iii.	A special point to note, is that the ingredients act on the immune system and the regulation of cytokine secretion, which is a different mechanism from the majority of the anti-asthma medication currently on the market.
iv.	It is not a systemic immunosuppressant, so the side effects are reduced.

(2) Techniques

i.	Chemical constituent identification: a strict quality control system, from raw materials, and formula fingerprint, through to the end product.
ii.	Approved natural extraction techniques: GMP process validation, and complete CMC techniques and experience are used for the whole plant raw materials.
iii.	Biochemical activity analysis of asthma treatment: the development of the drug pharmacology investigation model is focused on the factors that worsen asthma.
iv.	Asthma treatment efficacy evaluation is based on an animal model: the animal model was established by focusing on the symptoms found in human asthma patients, so further investigation can be made into the medication's efficacy and into possible pharmacological mechanisms.

(3)Experiment Results

Breathing was improved, because the methacholine caused bronchoconstriction -Lung function

ii.

Naive	Sensitized	1217B
Naive: the normal lung tissue, with pink color evenly distributed. Sensitized: ovalbumin sensitive mice without treatment 1217B: ovalbumin sensitive mice fed with BMEC-1217B DEX: ovalbumin sensitive mice fed with dexamethasone		DEX
Incomplete bronchi (without clear lines) and soaked inflammatory cells (indicated with the arrow) were observed in lung tissues from ovalbumin sensitive mice

iii.

Naive	Drug1217B
DEX	NS

Title of technology : 1217B- Asthma treatment

1217B is a botanically derived potential drug candidate that i nhibits the synthesis of several key pro-inflammatory mediators involved in the pathophysiology of allergic asthma and has been found to improve lung functionality in a mouse model of allergic asthma.

Description

Inhaled corticosteroids are currently the first line of treatment for asthma. However, these medications lack specificity in their effects and are often associated with side effects. There remains a need for the development of improved therapeutics for allergic asthma.

1217B, a complex mixture of botanical extracts, has been derived from four traditional Chinese medicinal herbs. It was studied for its pharmacological activity regarding the release of cysteinyl leukotrienes, IL-4 and TNF a in vitro and the airway hyperreactivity in an antigen sensitized-challenged mouse model in vivo . Preliminary results indicate that 1217B can inhibit the synthesis of several key pro-inflammatory mediators involved in the pathophysiology of allergic asthma and can also improve lung function in a mouse model of allergic asthma. Safety studies have also been performed on cardiovascular, respiratory, and nervous systems using 1217B, and results indicate that no side effects are caused. I n vitro tests and in vivo animal tests data are available on request .

Patent No

US patent issued, and EU, China , Germany , England and Taiwan patents are pending

Development status

USA FDA IND. I n vitro tests and in vivo animal tests data are available on request.

Type of business relationship sought

CAM oriented (alternative therapy) companies that are interest in marketing 1217B to help a sthma patients.
Biotechnology companies that are interested in developing 1217B into a drug following FDA guidelines.
Companies or research institutes that are seeking collaboration for commercial or scientific purposes.

This product helps relieve the side effects, such as leukopenia and the reduction of platelet, after cancer chemotherapy and radiotherapy, and can increase the quality of patient's life. The main active components of this product come from the extracts of Western and Oriental herbals, and have been proven to reduce the side effects resulting from cancer chemotherapy and radiotherapy. According to statistics, there are more than 10 million new cancer patients around the world every year. In addition to the removal of tumor by operation, most of these patients will undergo radiotherapy or chemotherapy to completely eliminate cancer tumors. Unfortunately, radiotherapy and chemotherapy often cause serious side effects, and will greatly lower the quality of the patient's life. Our product not only reduces the side effects caused by chemotherapy, but it also increases the number of leukocyte and platelet which helps lower the risk of recurring hemorrhage and infection during therapy. The greatest competitiveness of this product lies in the fact that it is a food product, nontoxic, orally taken, convenient to carry, and does not require in-patient treatment. This product has a potential to be developed into medicine, and has been verified by Ministry of Economy's industry specialty project, acquiring governmental subsidy for medicine development.

Title of technology: CA-88-Cancer chemotherapy and radiotherapy auxiliary treatment

CA-88 is a botanically derived auxiliary treatment that has been shown to exhibit healthful benefits for patients undergoing cancer chemotherapy and radiotherapy .

Description

CA-88 is a botanically derived compound that has been shown in preliminary studies to help relieve leukopenia, nausea, parageusia, quadriplegia, anesthesia and hearing loss, side effects that are associated with cancer chemotherapy and radiotherapy. CA-88 was developed based on the results of in vitro assays, in vivo animal model s and preliminary human studies. The product is a food product, nontoxic, orally taken, convenient to carry, does not require in-patient treatment, and has potential to be developed into medicine. In animal and preliminary human studies, CA-88 showed potential for elevating immune function to inhibit growth of cancer cells. Preventative cancer functionality was also exhibited on studies in a conventional BALB/c mouse, while preliminary toxicity studies showed no deleterious effects of the compound on the test subjects. I n vitro tests , in vivo animal tests and preliminary human clinical trial data are available on request .

Patent No.

USA , EU, Canada , Australia and Taiwan patents filed

Development status

Drug development – pre-clinical. I n vitro tests , in vivo animal tests and preliminary human studies are available on request .

Health food development – food product launched in 2005. I n vitro tests , in vivo animal tests and human clinical trial data are available on request .

Type of business relationship sought

CAM oriented (alternative therapy) companies that are interest in marketing CA-88 to help cancer patients.

Biotechnology companies that are interested in developing CA-88 into a drug following FDA guidelines.

Companies or research institutes that are seeking collaboration for commercial or scientific purposes.

This product consists components in the extracts from two herbs. It is used for preventing and treating the gastric ulcer caused by Helicobacter pylori or alcohol. According to IMS HEALTH, anti-ulcer medicine is one of the three best-selling therapeutic medicines in the world, the total sales in 2003 being an impressive 20 billion plus US dollars. At present, ulcer medicines are mainly Western medicines (anti-acid plus antibiotics), but no herbal medicine or foodstuff with high efficacy and low side effect. Our product, which is a food product, is effective even taken alone without antibiotics. Comparing with the nowadays two-in-one, three-in-one, or four-in-one standard treatment of anti-acid plus antibiotics, it is more convenient for users.

It can also reduce the possibility of developing drug resistance or other side effects caused by the use of antibiotics (for example, the destruction of the balance of bacterial flors). Recurrent and chronic ulcer patients, patients who refuse to use Western medicine or antibiotics, and patients who often eat out or who have weak intestines and stomachs, are our targeted customers for this product. This product is a food product, containing no antibiotics, is very safe, has no side effects, and is very competitive in price, making it a very competitive product. Recent studies has founded that the infection of Helicobacter pylori could increase the risk of stomach cancer and cardiovascular disease. This should make good selling point for our product.

Title of technology : MIC-31- Gastric ulcer treatment

MIC-31 is a botanically derived potential drug candidate for gastric ulcer prevention and therapy.

Description

MIC-31 is used for preventing and treating the gastric ulcer caused by Helicobacter pylori and alcohol. Infection with H. pylori is now found to be the cause of 90% of duodenal ulcers and 80% of gastric ulcers. MIC-31 was developed based on the results of in vitro assays, in vivo animal models and preliminary human studies. Both a nimal studies and preliminary human studies have shown that MIC-31 creates significant gastroprotective action against the ulceration caused by Helicobacter pylori . I n vitro tests , in vivo animal tests and preliminary human clinical trial data are available on request .

Patent No

PCT and Taiwan patents filed

Development status

Drug development – pre-clinical.

Health food development – food product launched in 2005. I n vitro tests , in vivo animal tests and human clinical trial data are available on request .

Type of business relationship sought

CAM oriented (alternative therapy) companies that are interest in marketing MIC-31 to help ulcer patients.

Biotechnology companies that are interested in developing MIC-31 into a drug following FDA guidelines.

Companies or research institutes that are seeking collaboration for commercial or scientific purposes.

i.	World Health Organization (WHO) warns that “obesity will become a global epidemic”
	Increasing obesity has now become a global trend. WHO declared in the opening ceremony of the 33 rd Annual Session of Standing Committee on Nutrition (SCN) on March 13, 2006 , that worldwide around 170 million children are underweight and nearly 300 million adults are obese . WHO hoped that, through this annual session, a program of action could be established in each country to solve both the problems described above at the same time. Of the 170 million underweight children, nearly three m illion die each year. At the same time, a statistics showed that about a billion adults worldwide were overweight, of which 300 million were obese. WHO warned that “being overweight or underweight is not a simple problem as a country's wealth or poverty, but it is related to the development of an individual, a society and a nation”. Statistics indicate that the life expectancy of obese people is nine years shorter than in the normal population . From a general health point of view, problems such as diabetes, hyperlipidemia, gallbladder disease, heart disease, high blood pressure, osteoarthritis, and gout, is more than three times higher for obese people than in the normal population; while the ratio of cancers and hormone imbalances is 1-2 times higher than the normal population. Diabetes caused by obesity has increased 55% in the past 40 years in the U.S. , which was just about the same percentage as the increased number of obese people. Moreover, the chances of getting digestive system diseases, varicose veins, endocrine and metabolic diseases, fatty liver, infertility, and respiratory dysfunction for obese individuals are also higher than for normal individuals. In addition, obese people might be excluded and discriminated against by society, their chances of getting education and jobs might be reduced, interpersonal relationships and married life would be affected, and finally, obese people might get autism and depression. Therefore, the disease of obesity can cause problems on the physiological, mental and social levels, which should not be neglected.
ii.	Weight Loss Market
	According to a statistics from the International Obesity Taskforce (IOTF), 1.7 billion of the world's six billion population is overweight! It is estimated that the global weight loss market is worth US$ 370 billion per year (the market for male treatments stands for US$ 50 billion dollars per year). The obesity rate in the U.S. is 61% , and the U.S. government intends to spend 75 billion U.S. dollars on the problem of obesity in 2003; in the U.S. alone, 500 thousand people directly or indirectly died from obesity in 2003. In addition, the obesity rate in the U.K. is 51% (about half of the adult population are having problems stemming from overweight or obesity); the obesity rate for Russia is 54% and for Germany , 50% . Statistics from the Worldwatch Institute show that, in Europe , more than half of the adult population aged from 35 to 65 is obese. China was listed on world obesity charts for the first time at the 11 th European Congress on Obesity in Vienna . Data from the last 10 years shows that the increase in obesity for Chinese was close to rate of increase in obesity in the U.S. for the past 50 years, which suggests that the obesity problems should not be neglected in the emerging countries, either. According to the information from the 8 th International Congress on Obesity held in California of the U.S. in 2000 , the U.S. ranked first on the global obesity chart. Although European countries did not rank as high as the U.S. , the condition was also very severe. Emerging countries cannot escape the fate of having an obesity phenomenon; 60% of the total population is obese in Mexico , while 1 in 12 males and 1 in 16 females in China suffered from obesity problems, and those figures are increasing rapidly year by year. The cover story of Business Weekly magazine Issue 824 in September 2003, asked the question “Do you know how many people are obese in Taiwan ?” and the answer was a third of the population, which was 6.99 million fat people. According to statistics, the obese population of Taiwan in the past 20 years has increased from 12% to 44% in 2004, which exceeds 10 million people. The Department of Health published a report which showed that weight loss market to be worth NT$100 billion in 2001 and that it had exceeded NT$200 billion in 2004 .
iii.	The Variety of Weight Loss Treatments
	There are six major types of mechanisms for weight loss treatments in the market:
	(1)	Metabolic Blockers
		• Glucose absorption inhibitor: av oid fat ac cumulations. For example HCA from the Garcinia cambogia extract is similar to citric acid, so is able to compete with the activity of ATP-Citrate lyase; thus, the process of conversion of excess glucose to fat will be interrupted. HCA is a mild weight-losing component, so the problem of recurrent obesity may happen easily. • Fat absorption inhibitor: avoid new fat accumulations. For example, Xenical weight loss medication, which acts mainly by the inhibiting the fat-digesting enzymes. Xenical inhibits the action of lipases in the gastrointestinal tract and avoids fat digestion. The undigested fat particles are too big for absorption by the human body, which reduces about 30% of the fat absorption from food. However, long-term use will produce undesired effects, including decreased absorption of fat-soluble vitamins A, D, E, and K, eye or skin complications, calcium absorption or blood coagulation deficits, aging of the skin…etc.
	(2)	Metabolic Inducers
		• Speed up the glucose metabolism: avoid new fat accumulation; promote factors of glucose metabolism to accelerate the processes in the glucose metabolic pathway. For example, the vitamin B group has this function. • Speed up fat metabolism: metabolize the accumulated fat; promote factors of fat metabolism to accelerate the processes in the fat metabolic pathway. Unsaturated fatty acids include docosahexaenoic acid (DHA) , eicosapentaenoic acid (EPA) , and evening primrose oil (EPO) , which are able to promote fat metabolism.
	(3)	Neurotransmitter Inhibitors
		• Prolong the reaction time of norepinephrine and serotonin in the brain to increase the metabolic rate and promote fat consumption in cells. However, the undesired side effects include insomnia caused by an over-stimulated central nervous system (CNS), nausea, constipation or palpitations. An example for this kind of mechanism is Reductil weight loss medication, and it has problems with recurrent obesity. The U.K. Health department announced that two people had died from using Reductil, with more than 200 people suffering undesirable side effects. After the human clinical trial performed with Reductil medication 34 volunteers died, but it was common to see obese people suffering from heart disease or diabetes. Therefore, the mortality rate for Reductil medication is still lower than the 1% mortality rate in the obese population without the medication. Pharmaceutical companies received 28 reports of death from the U.S. , two each from Italy and the U.K. , one each from South Africa and Switzerland . Until now, nearly 9 million people have used Reductil medication, and about two in every 100 thousand users of Reductil treatment die each year. According to other research, about 400 in every 100 thousand people die from obesity related causes each year. • Phenylpropanolamine (PPA) is a major medication for the common cold, the characteristic for this treatment is sympathetic nerve stimulation and inhibition of the feeding center of hypothalamus, which is able to decrease the appetite. The medication's activity is similar to ephedrine and amphetamine, but it is not addictive. The mild undesired side effects include dry mouth, palpitations, insomnia, vision and conscious disturbances; severe effects are suspected to brain hemorrhages and stroke.
	(4)	Body water and waste digesters
		Laxatives are the main items in this category. Common medications include magnesium oxide and sennoside; they mainly act in the gastrointestinal tract, causing intermittent diarrhea in this way, the water and waste contents inside the body will be removed. Undesired side effects will be caused by the condition of long-term diarrhea, which affects nutrition absorption activity leading to anemia and malnutrition. If users are over-dependent on the medication, it will result in constipation and intestinal dysfunction; in more severe cases, dehydration, an imbalance between water and electrolytes, and fainting may happen.
	(5)	Appetite controllers
		• Meal replacements contain several nutrients; if an individual has three meal replacements each day, the calorie intake may be insufficient. Since the standard calorie intake for a dieting person should be 1000-1200 Kcal, people who have three meal replacements per day will easily give up on dieting and resume their normal diet again with recurrent obesity problems. However, the meal replacements are convenient due to the fairly balanced nutritional content. It is suggested that dieters take 1-2 meal replacements each day, so the low-calorie characteristic of the meal replacement can be combined with a normal balanced meal, which will be gradually reduced day by day. Some meal replacements taste bad, which does not satisfy the human desire to eat good-tasting food. • High fiber diet, including whole wheat or grains containing abundant fibers, will absorb water and expand in the stomach to make people feel satiated and decrease the appetite. The food fiber will not be used and digested in the human body; however, fibrous foods are nonfat with an unattractive taste, so people are always reluctant to eat them continuously, but instead increase the amount of their other food intake, leading to obesity. • High protein diet contains mainly food with protein source and excludes glucose and fat intakes; but the unbalanced nutritional intake will lead to abnormal physiological and metabolic activity.
	(6)	Metabolic integrators
		Combined weight loss medication is an all-purpose and most complete formulation, through the promoted biochemical metabolism and inhibition on the integrated regulation , weight loss will be achieved. The complex mechanisms are as follows: inhibiting the new fat formation converted from excessive glucose, promoting glucose metabolism to avoid new fat accumulation, inhibiting excessive fats accumulating, accelerating the metabolism of the accumulated fats and transforming them into energy source. The metabolic integration will be based on safety and balance to regulate the body metabolism; the weight loss mechanism will not be a one-way or a biased complete disruption or acceleration. The biochemical metabolic regulation will be adjusted according to the status of your body.
iv.	Weight Loss Concepts: Safe, No Side Effects, Gradual Progress
	The correct weight loss method should be based on a balanced diet and a modification from the previous eating and living habit; the best way needs to accompany an appropriate amount of weight loss with food and exercise. The safe range for weight loss is 1 -5 kg /month. Individuals suffered from a long-term high body fat level would require more time to achieve weight loss; it is recommended to control the calorie intake within the required range. During the weight loss period, the metabolic function must be normal and it is inappropriate to have diarrhea or other significant abnormal physiological changes. If the speed of weight reduction is not controlled, the body may be damaged, causing six major symptoms as follows:
	(1)	Recurrent Obesity
		The weight lost within a short period of time will be regained easily; the individual may become even heavier than the previous heaviest weight. If the weight is regained, it will be more difficult to reduce again to the ideal weight. The condition of weight fluctuation, like a yoyo going up and down, always happens to habitual dieters. Excessive weight loss in a short amount of time will dehydrate the body, decrease the amount of muscle and fat tissues, and, of course, the weight will be reduced. However, if recurrent obesity happens, the weight will be regained mostly in the form of fat.
	(2)	Decreased Metabolic Rate
		The basic human metabolic rate provides the need of normal physiological functions and maintains life,(for instance, heartbeat, breath and gastrointestinal peristalsis...etc. ) Basic calorie consumption is required for the processes mentioned above, but individuals who experience rapid weight loss usually get insufficient calories. When the calorie intake is lower than the basic body needs, to keep normal physiological function, the body will adjust the metabolic rate, so the basic body needs and the calorie consumption will be lowered. At this stage, if the individual returns to the normal diet with the previous calorie intake, it will become a relatively excessive calorie intake as seen by the lowered and modified metabolic rate. This is the cause of recurrent obesity and the source of excess calorie intake.
	(3)	Weakened Immunity
		Since most rapid weight losses result from low calorie intake, accompanied with unbalanced nutrition or insufficient nutrient intake, and rapid muscle protein depletion, the body strength will weaken. Consequently, immunity deficiency will occur and the amount of lymphocytes will be decreased; of course, the defense system of the body will be weakened and the individual will catch cold easily with frequent back soreness.
	(4)	Irregular Menstrual Cycles
		For females, the most obvious warning sign of too rapid weight loss is in the menstrual cycle. The normal menstrual cycle is 28-30 days; although it varies individually with different body types, there should be a stable cycle. However, when the weight lost is significant, the most frequent consequence is an irregular menstrual cycle; in a more severe condition, the menstrual cycle will be stopped. Inappropriate dieting has adverse effects on the female hormones, thus stopping the menstrual cycle or causing menstrual cycle disorders.
	(5)	Hair Loss and Poor Skin Condition
		Most rapid weight loss is caused by malnutrition, which causes abnormal metabolism in the body and leads to hair loss, withered hair, and dried hair in severe conditions. Skin condition will also worsen, it will be rough, and acne is more likely when the nutrient intake is insufficient hormone metabolism is abnormal.
	(6)	Body Organ Disorders and Dysfunction
		Under a long-term condition of hunger, the calorie and nutrients intakes are insufficient, at the same time, a large amount of water is lost from the body; as a result, proteins inside the muscle will be digested, leading to liver and kidney dysfunction. Moreover, the repetitive weight loss activity and decreased metabolic rate will affect gastrointestinal function, causing poor digestion or other gastrointestinal diseases.

Medigreen Biotechnology Corporation, working conscientiously and professionally, continues to investigate and develop products for diabetes, liver diseases, cancer, and anti-depression, to benefit the public and create business opportunity.

Period

Title of Project

Type

February,2003 ～July,2003	The initial stage of research project for traditional Chinese herbal medicine extraction AT-21 to reduce the side effect of cancer chemotherapy	Small Business Innovation Research (SBIR)

July, 2003～September, 2004	the Program of Strategic Platform for International Herbal Medicine Regulations, Strategy Five: Herbal Medicine, LeukoGreen	Industrial Technology Development Program

Item

Patent Title

Application Area

Application Date

1	Method of using geranium oil and sophora root extracts as a supporting composition in cancer treatment	America	2002.10

2	The employment of aromatherapy and pagoda tree extraction for the assistant therapy of cancer	Taiwan	2002.10

3	Composition and Method for Supporting Cancer Treatment	PCT	2003.04

4	The use of the compound and its method as assistant therapy in cancer therapy	Taiwan	2003.04.

5	Method of Use of Herbal Composition	America	2003.07