FIELD OF INVENTION

UNIQUE POTENT DIETARY FOOD SUPPLEMENT (ANDAM-1) FROM ANDAMAN FRUIT (Morinda Citrifolia commonly known as 'Noni') BY FREEZE DRYING METHOD, TREATMENT FOR CURING CANCER, CARDIOPROTECTIVE & HYPERLIPEMIA WITH OTHER PROPERTIES/POTENTIAL HEALTH DIEASES.

BACKGROUND OF INVENTION:

The invention relates to a unique one, first of its kind for the preparation of Dietary Food Supplement in POWDER FORM from fresh fruit of noni of Andaman Islands origin (India) duly incorporated with suitable macro-nutrients & micro nutrients and suitable pharmaceutical excipients and possesses ANTICANCER, CARDIOPROTECTIVE HYPERLIPIDEMIE and other properties with no side effects.

PRIOR ART :

Scientific Research on Morinda Citrifolia Linn (Noni or Indian Mulberry) since 1990 to 2005, highlights the use of roots, Bark stem, leaves, fruits of Noni for isolation of various form of pharmaceutical Chemicals for treatment of Virtually all types of disease of HUMAN and Pet animals. They are as follows:-

NONI RESEARCH 2001 -2010

1) Morinda Citrifolia & Cancer Prevention: In-vivo study (conducted in a living cell or organization), TAHITIAN Noni - Juice reduced DNA adducts (chemical changes in DNA that result in damage) caused by carcinogen, 7, 12- dimethylbenz (a) anthraeene(DMBA). TNJ showed stronger anti oxidant activities' compared to vitamin C Grape seed powder & Pyonogenola. TNJ's antioxidant contributes to the mechanics of reducing DNA adduct formation, (study by Wang W-Y, July 2001)

2) Protective effect of "Noni" on Carbon Tera Chloride CC1 ₄ _ Induced liver injury in Female sd Rats. In an in - vivo study, Tahitan Noni -Juice showed hepatic protection in rats damaged liver caused by CC1 _4. The antioxidant level was examined and the results indicated by the scavenging free radicals and blocking Lipid preoxidation.

3) Agricultural Food chemistry. 49(9 : 4478. 4481: 2001 in the Article

"FLAVONAL GLYCOSIDES AND Novel Iridoid Glycoside from the leaves of MORINDA CITRIFOLIA L. (Noni) research conducted by Mr. S. Sang, Mr. X Cheng, Mr. N. Zhn et.al. stated "One New IR1DOID GLYCOSIDE (defensive compounds produced by plants) and five known FLAVONAL GLYCOSIDES (which functions on antioxidants) were isolated from the leaves of MORINDA CITRIFOLIA. Their antioxidants (free radical scavenging) potential was measured, and all compounds showed antioxidant activity.

4) THE WORLDNUTRA, 2004 conference poster session # 30 TOTAL Antioxidant capacity (TAC) of Noni Products as Affected by Processing & storage:-

"Tropical Noni (MORINDA CITRIFOLIA L) fruits are processed commercially into juice and powders for disease preventation and therapies. The total antioxidant capacity (TAC) of fresh squeezed noni(Vitamin C)/ 100 ml assayed by scavenging the free radical traditional fermentatuin decreased the TAC of noni-juice by 70%. Noni Juice stored at 24° C for 2 months reduced TAC by 80% Fresh Noni Juice stored at 18°C for 2 months exhibited no significant changes of TAC. The TAC of NONI POWDERS dehydrated by hot air or freeze drying was reduced by 45% & 20% respectively.

5) QUALITY OF LIFE RESEARCH - official Journal of the International Society for Quality of Life Research (ISOQOL) 14(a): P-70/134Z. 2005

Abstract presented at 12 ^th Annual Conference of the International Society for Qualtiry of Life Research (ISOQOL), Quality of life (QOL) Assessment in a Phase I Trial of Noni-

Authors: B.I.Issell., C.A. Gotay, I. Pagano, Cancer Research Centre of Hawaii University of Hawaii, Honululu, HI

# The Objective of this study was to identify the maximally tolerated dose (MTD) of noni. Noni Fruit extract is a popular dietary supplement that is widely used as complementary and alternative medicine (CAM) by CANCER patients. 29 patients were assessed. The distribution of performance status, extent of diease and prior treatment did not vary across dose levels. A multi level regression analysis of noni dose (2,4,6,8, 10 g) and a week of study showed a statistically significant[t(35)=2.84, P=0.006] decrease in pain interference with activities as measured by the question 19 on EORTC QLQ -C30 scale. Also consistent marginally significant dose-response effects were found for global health status, physical functioning and fatigue.

No effects were found on the BFI and CES-D. No Toxic events attributable to noni and no tumor regressions were seen.#

Conclusion: QOL measures may be useful for selecting dosing for subsequent phase ΐί/ΙΙΙ efficiency trials, particularly for CAM agents that are commonly used but of unproven value.

6) ACTA PHARMALOGICAL SINICA. 23(12): 1 127-1 141. 2002

Morinda Citrifolia (NONI) : A literature review and Research advances in Noni Research:

"ANTITUBERCULAR Constituents from hexane fraction of Morinda Citrifolia Linn. (Rubiaceae). Authors: Saludes, Jonel P, Garson M.J, S.G. Franzblau, A.M Aguinaldo.

A crude Ethanoe extract and Hexane fraction from Morinda Citrifolia Linn (Rubiaceae) show antitubercular activity. The major constituents of hexane fraction are E-phytol, Cycloartenol, Stigmasterol,sitosteral, campesta-5,7,22-trien 3-ol and ketosteroids stigmasta-4-en-3-one and stigmasta -4-22-dien-3-one. E-phytol a mixture of the Ketosteroids and the epidoxysteroid derived from campesta-5M22-trien-3-01 all show pronounced anti tubercular activity. 7) Immunostimulant activity of noni(Morinda citrifolia) on T and B lymphocytes

July 2010, Vol. 48, No. 7, pages 724-731 (doi: 10.3109/13880200903264434)

Smita Nayak, Sushma Mengi

Morinda citrifolia Linn (Rubiaceae) is a traditional medicinal herb that has been purported to be beneficial in the treatment of infevtions due to its immune enhancing properties. However, detailed studies highlighting the effect of different compounds isolated from the plant on the immune system are lacking. In this study, the stimulatory effects of the extracts on lymphocytes were assessedby in vitro (MTT assay) and in vivo(cell mediated immune response) techniques. Results of the MTT study indicated that the hydroalcoholic (0.5 and l .Omg/mL) and aqueous extracts (0.5 and l .Omg/mL) significantly (p<0.05) increased in vitro splenocyte proliferation to the extent of 43.6, 54.5,32.7 and 36.4% respectively. Moreover, the hydroalcoholic (200 mg/kg) and the aqueous (200mg/kg) extracts significantly (p<0.05) increased the cell-mediated immune response to the extent of 33.52 and 18.56%, respectively. The fractions F I, F ΙΪ and F 111 failed to elicit a significant stimulatory effect on lymphocytes in the in vitro and in vivo studies. The effect of the extractives of M.citrifolia fruits on B-cells was measured by the delayed type hypersensitivity method. The study revealed that the hydroalcoholic ectract (200 mg/kg) and fraction F 1(40 mg/kg) significantly increased that the humoral response to the extent of 33.33 and 35.12% respectively. The results of this study confirm the cellular and humoral immunostimulant properties of M.citrifolia fruits and justify its usage in traditional medicine.

3 A) Medicinal Active Components found in "NONI JUICE"

Medical value are formed throughout the plant i.e. leaves flowers barks and stalks were traditionally used to treat wide range of diseases but it is the fruit which stores the essence of the plant NONI FRUlT contains 140 plus neutraelntical compounds and other active constituents including enzymes alcoloid anthraquinones phytonutrients minerals and vitamins are identified so far as furnished below.

Acetic Acid Acubin Alazarin Alkaloids(xeroninepyuxeronone)Anthraquinones Asperuloside Beta-sitosterolButanoic AcidBenzoic Acid Benzyl Alchoholl-butanol Calcium Caproic Acid, Caprylic Acid, Damnacanthal,Decanoic Acid, CE-6-do deceno-gamma-lactone (z,z,z)-8,l l,14- eicosatrieonic Acid Elaidic Acid, Ethyl decanonate,Ethylhexanoic Acid,2- heptanone,Hexanal,Hexanamide, Hexanedioic Acid, Hexanoic Acid, I-hexamol,3-hydroxy-2- butanone, iron, Lanric Acid, I-asperuloside, Limonene, Linoleic Acid, Morindone, Morindine, 2- methylbutanoic acid,3-methyt-2-buten-l-ol, 3-methyl-3-buten-l-ol, Methyl deconate, Methl palmitate, 2-Methylpropanoic Acid, 3-methylthiopropanoic acid, Minerals, Myristic Acid, Palmitic Acid, Polysaccharide, Phytonutrients, Potassium, Serotonin, Scepoletin Selenium, Terpene Compounds, trace elements, undecanoic acid (z,z)-2, 5-um decadien-l -ol, Vitamins ((Vitamin A,C, betacarotene, Niacin, Ruboflouin,Thiarnine), Vomifol. Noni is anti cancer agent more effective than 5 OOother botanical isolated testedin converting cancereous cells back into normal cells. 3B. The illness and disease cured by NONI are as follows:

Addictions, Aging , AIDS, Allergies, Asthma, Artherosclerosis, Blood Vessel, Broken bones, Burns, Bruises, Cancers, Cataracts, Cell regeneration, Chronic back pain, Chronic fatigue, Colitis, Cuts, Depression, Detoxofocation, Diabetes, Digestive problems, Energy boost, Fibromyalgia, Headache & Migraine, Heart disease, Stroke, High blood pressure,

High cholesterol Immunity-T cell count, Increase energy, Infectious disease,

Inflammation, Insomania, Intestinal parasites, kidney health, lupus, Menstrual cramps, Multiple slerasis, Weight problem,(over/under weight), esteoarthiritis, Pain, Psoriasis, Crohn's Disease, Respiratory ailments, Senility, Sexual Viability, sinus, Skin problems, Eczema acnes, Tumor, Mamary breast, Cancer, Prostrate tumor, Oborty, Central nervous system, obesity, Muscle Contraction, Nausea, Endocrine regulation, Hypertension, Austism, Alzheimer's disease, anxiety disorders, drug and alcohol addiction, patterns of violent behaviour, powerful body detoxifying agent and is a natural antioxidant to help rid the body of toxins, Tuberculosis etc.

4. OBJECT OF INVENTION:

Scientific Name of plant "Morinda Citrifolia Linn" belonging to Family RUBICEAE or Indian Mulberry commercially known as "NONI" grows widely throughout Pacific Island, Australia, Indonesia, South-eastern Asia & Tropical countries. It is noted for its extremely wide range of environmental tolerances viz. it can grow in infertile acidic and alkaline soils,very dry to wet areas; it can tolerate exposure to wind, fire, flood, saline soil conditions as well as lava flow.

All parts of plant have traditional and/or modern uses including roots and bark (dyes, medicines) trunks (firewood, tools) & leaves and fruits (food, medicines).

The tree has attained significant importance worldwide in recent years through a variety of health and cosmetic products made from its leaves and fruits-. The plant is adapted to the propics 1 to 800M(MSL) having mean annual temperature 20 to 35° C with annual rainfall of 250 to 4000mm. Growthrate-moderate,0,75 to 1.5mts/year and attains 3-8 meters height at maturity. It is associated with a wide range of coastal & littoral shrubs, as well as with numerous cultivated plants.

"Noni Fruits" are large, fresh and ovoid. The fruit matures from dark green to 12cm, creamy- white-yellow. It has lumpy surface covered by polygonal shaped sections. The flesh is usually milky white, juicy with a fetid odour. The seeds are triangular shaped and reddish brown have an air-sac at one end. The fruit is not quite palatable because of its bad taste and smell. Juice extraction is difficult due to large amount of foam and multiple seeds in the fruits. The challenge is to extract Noni juice in a natural way to remove its pungent smell and taste, and yet preserving its natural state without destroying its highly sensitive medicinal compounds.

4.1) The object of invention is conversion of NONI FRUIT JUICE to HUMAN DIETARY FOOD SUPPLEMENT IN POWDER FORM in -order to cure the disease and illness as enunciated in ( stated in para 3B) above. 5. STATEMENT OF INVENTION

# The invention of manufacturing New Dietary Supplement. ANDAM-1 is as follows:

5. a/Step 1 : Fresh Noni fruits were collected from Andaman Island (INDIA) in the month of May. It may be observed that the fruits can be collected throughout the year.

5.b/step 2 : The fruits were thoroughly washed with De-mineralized(DM) water and cut into small pieces.

S.c/Step 3 : All the pieces were dipped into a solution containing suitable preservatives for half an hour.( 30 minutes)

S.d/Step 4 : Then all the pieces were deep frozen at -80 ° C for hours(i.e freeze bried). S.e/Step 5 The deep frozen fruits from Step 4 were dried in a Lyophilizer at -45 X! and 30mm/Hg (vacuum Pressure) until its moisture content becomes 6%(by weight).

5.f/Step 6 : The dried material (so obtained by Step 5) was ground asceptically and passed through mesh size 10 to 12.

5.g/Step 7 Suitable food grade pharmaceutical excipients were mixed with the powder, thoroughly in a de-humidified condition.

S.h/Step 8 Dietory Powder of "Noni" was powdered into pouches and is thus ready for marketing.

6) SUMMARY OF INVENTION (VIDE 6A & 6B)

Furnished below are the composition of the constituents i.e macro & micro nutrients of our invented "Freeze Dried Powder" vis-a-vis "pure noni Juice". It may be mentioned that the "Freeze dried Powder'Of Noni is highly potent than Noni Juice; the former therefore can be used as Dietary Supplementary Food to both humans and Pet animals, as invented by us.

6A) COMPARATIVE STUDY OF MACRO AND MICRO NUTRIENTS PROFILE FOR NONI FRUIT "FREEZE DRIED POWDER" + NONI FRUIT JUICE

NB: - (1) Freeze dried Powder or as invented by us:

With the Freeze Dried Powder, suitable food grade exciepients are mixed thoroughly in a dehumidified condition, to form the " Dietary Powder of Noni" duly stored in special condition and in parked pouches before it is to be dispatched to markets.

6B) Research Findings of Noni Extract in curing various disease; (summary of Invention)

1) ANTITUMOR AND ANTICANCER EFFECT OF NONI EXTRACT

• In 1992, Hirazumi, reported anticancer activity from the alcoholic precipitate of Noni fruit on lung cancer in C57 BI/6 mice.

• The noni-ppt was shown to significantly prolong the life of mice upto 75% with 1 implanted Lewis lung carcinoma compared with the control group.

. · Recent study by Dr. Wang demonstrate that a cytotoxic effect of Noni on cultured leukemia cell line t various concentration.

• The cytotoxicity was shown by inducing cancer cell necrosis at high doses and apoptosis at lower doses.

• The synergistic effects of Noni with known anticancer drugs have also been found. CANCER PREVENTIVEEFFECT OF NONI AT THE INITIATION STAGE OF

MAMMARY BREAST CARCINOGENESIS

The cancer preventive effect of Noni at the initiation stage of mammary breast carcinogenesis, induced by DMBA(7- 12-Di-methyl Benz-Anthracene), was examined in female Sprague-Dawley(SD) rats.

Noni was continuously supplied for 90 days after DMBA administration. All the animals were sacrificed 8 ^th month after DMBA administration to examine the pathological changes in the mammary glands by light microscopy.

Compared to controls; the DMBA treated group showed a variety of lesions, including epithelial hyperplasia(12.5%), benign tumors(25%), and in situ carcinomas(25%).

No benign tumors or carcinomas were found in the noni group, which showed normal histology or mild hyperplasia.

These results indicate that Noni may prevent mammary breast cancer at the initiation stage of chemical carcinogenesis.

ANOTHER CANCER PREVENTIVE EFFECT AT THE INITIATION STAGE OF CARCINOGENESIS BY NONI

Prevention of chemical carcinogen-DNA-adduct formation Female SD rats by noni was investigated

Three animals from each group received intra-gastrically 25 mg/kg of DMBA containing 5% dimethysulfoxide in corn oil.

After sacrifice DNA was isolated from rat liver, lung, heart and kidney and DNA adducts were analysed by ² P-post labeling technique.

The noni group showed a reduction in both the number and level of DMBA-DNA adducts from each of the four organs studied.

The quantative estimate after radioactive counting indicated that noni reduced the amount of DNA adduct formation by 80% in kidney, 42% in liver, 41% in lung and 26% in heart.

Page 7 of 17

PROACTIVE EFFECT OF NONI ON LIVER INJURY INDUCED BY A LIVER CARCINOGENfCCLT)

In a study, the preventive effect of noni on carbon tetrachloride(CCL|)-induced liver injury in female SD rats was examined by light microscopy (LM) and electron microscopy(EM) examination.

Liver sections placebo and noni groups demonstrated normal lobular architecture and normal ultra structure at the LM level.

There was a significant decrease in the number of swollen, lipid containing, and apoptotic hepatocytes in the noni + CCL ₄ group, compared to the placebo + CCL ₄ at the EM level. 5) CARDIOPROTECTIVE & HYPOLIPIDEMIC ACTION OF NONI

• Noni appears to be cardioprotective by reducing risk of atherosclerosis and lowering blood pressure.

• The extract up-regulates the low-density lipoprotein (LDL) receptor, which leads to accelerated LDL clearance from, the circulation.

• Furthermore, a Japanese study indicated that noni strongly inhibited the activity of angiotensin I converting enzyme.

• Noni regulates serum lipids by lowering the cholesterol, triglyceride, low-density lipoprotein(LDL) and very low-density lipoprotein(VLDL) levels, and restores the cardioprotective high-density lipoprotein(HDL).

• It also reduces platelet aggregation and the sensitivity of the heart to adrenergic stimulation and improves the contractility of the heart by exerting a positive inotropic action.

7) BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING

7.1) FLOW SHEET DIAGRAM OF INVENTION OF A ^' NEW DIETARY SUPPLEMTNT (ANDAM-1) as per above steps of manufacture is enclosed in the following page 6 of 17 and the experimental results pertaining to the steps of steps is here as under:

7.2) The freeze dried methanol and water partitions were scanned on 260-700mm by JASCO V- 650 spectro photometer a) Fig 1: The graph shows spectra analysis of water extract of noni,(vide pg 7 of 17) b) Fig 2: The graph shows the spectra analysis of methanol analysis of Noni,(vide pg.

8 of 17)

7.3) HPLC Analysis of methanol extract of Noni in Fig 3 with results in tabular form is given, (please vide page 9 of 17)

7.4) HPLC Analysis of water Extract of Noni in Fig 4 with results as tabulated therein.(please vide page 10 of 17)

2) While the small cut pieces of Noni Freezed dries at -80°C for 12 hours as, per Step 4 were dried as in Step 5, at -45° C at 30 mm Hg (vacuum pressure) in a Lyphoilizer until its moisture content becomes 6% (w/w). This can be achieved by "LASER" or "MASER" (under controlled condition of heating to raise from -80° C to -45°C i.e. by -35°C incremental temperature), without tampering the potency of the constituents, of Noni. The related graphs ot item ana D.I

explanatory for solvent extraction of Noni-fruit juice by ethnol (CH ₃ OH) & water (H ₂ 0) as per above steps of Invention.

7. A) Deviations in the invention are:

1) The oral dosage noni formulation as per the Patent Document No.

US20020172730 and US20050238735 claims Noni Oral Extract formulation. (in the invention) which reduces or eliminates strong disagreeable taste while simultaneously increasing the efficiency of a NONI ORAL EXTRACT DOSE. The "solution" as indicated in Step 3 under statement of Invention para 5.c is our Trade Secret. ·

8. DETAILED DESCRIPTION OF THE INVENTION WITH REFERENCE TO BIBLIOGRAPHY, REFERENCES, PATENT FILED . PATENT SEARCH. PATENT OBTAINEDA BIBLIOGRAPHY.

"Noni" the wonder plant of the nature is rendering healing services to cure illness and diseases of human and pet animals since 2000 years or before, it was a native plant of Polynesia. The Polynesian tribals were aware of its redmedial measures for health cure. Now it is most sought after because of its medicinal value, skin care, cosmetic applications apart from those explained under para 3B. A lot of literature and studies/ articles/ research papers are available today in various countries. The stated research papers addresses to a particular aspect of curing a type of disease only, considering the part of plant (roots, bark, stem, leaves, stalk, fruits) being the focal point. Noni Juice product is also used as cosmetics and treatment of skin tumors.

MEDICINAL FOOD:7:343-348.2004 , The evolution of nitric oxide (NO) scavenging activity of In vitro: A preliminary study- by J.S. Jagecia & M.S. Baliga

The authors concluded that the NONI plant ranked 3 (amongst 17 Indian medicinal plants which are commonly used) is having potent and novel therapeutic agents for scavenging of NO and the regulation of pathological conditions caused by excessive generation of NO and its oxidation product, peroxynitrite.

B) REFERENCES

• Furausawa E, Hirazumi A, story S, and Jensenn J. Antitumour potential of polysaccharide-rich substance from the fruit juice of Morinda Citrifolia (noni) on Sarcoma 180 ascites tumour in miee. Phytotherapy Research. 2003: 17: 1 158-1 164.

• Arpornsuwan T and Punjanon T. Tumor cell-selective antiproliferative effect of the extract from Morinda citrifolio fruits. Phytotherapy research. 2006; 20:515-517.

Page 14 of 18 Yamaguchi S, Ohnishi J, Sogawa M, et al. Inhibition of angiotensin I converting enzyme by noni (Morinda citrifolia) juice. Journal of the Japanese Society of Food Science and Technology. 2002;49(9):624-6273

Kim S-W, Jo B-K, Jeong J-H, et al. Induction of extracellular matrix sythesis in normal human fibroblasts by anthraquinone isolated from Morinda citrifolia (noni) fruit. Journal of Medicinal Food. 2005;8(4):552-555.

Palu Ak, West B, and Jensen J. "Not all Noni liquid dietary supplements are created equal."Am J Hematol. 2005 May; 79(1 ):81

Carr ME, Klotz J, Bergeron M. Coumddin resistance and the vitamin supplemen 'Noni".. [Letter]. American Journal of Hematology. 2004;77: 103.

McClatchey W. From Polynesian healers to health food stores: changing perpectives of Morinda citrifolia(Rubiaceae).Integrative Cancer Therapies. 2002; 1(2): 1 10-120.

Wang M, Kikuzaki H, Csiszar K, et al. Novel trisaccharide fatty acid ester identified from the fruits of Morinda citrifolia (Noni). J Agri Food Chem. 1999;47:4880-4882O PATENTS FILED:

Awaited clearance upto 13/09/2010 ¹

i) US PATENT APPLICATION 5288491 (Filed 1992) ":Noni (Morinda Citrifolia) as a Pharmaceutical Product" by Mr. Herbert Moniz. The invention relates to a method for processing the noni plant into powder.

ii) US PATENT APPLICATION 2010046550(Filed 2001) "N (Morinda Citrifolia) Dietary Fiber - by Mr.L. Wadsworth, J. John, Story, P. Stephen, Jensen, C. Jarkae. A dietary fiber product from the India Mulberry (Morinda Citrifolia Linn.) fruit and the process of extracting and purifying the fiber is disclosed. High fiber products can be prepared by mixing the pulp with ingredients such as dietary fiber, ¾0, sweeteners, flavouring and colouring agents and nutritional ingredients.

D) PATENT SEARCH were done through

i) http:// www.bing.com/search

ii) http:// www.patentstorm.us/search

iii) http:// www.noniresearch.org/united-states

iv) http:// brevets-patents. ic.gc.ca/opic-cipo/cpd

v) http://www.freepatentsonline.com

9E) PATENT OBTAINED:

With respect to "Freeze Dried Dietary Supplement of Noni Fruit Juice in powder form" no patent has vet been obtained by the researchers in this field or has been awarded by any country for NONI POWDER

i) However, Indian Noni (www.indian-noni.net ^' ) ascribes noni as a dietary supplement, obtained from the extracts of Morinda Cirtifolia, an Indian Medicinal Plant. Ancient Ayurvedic Text acknowledges its medicinal attributes.

Page 15 of 18 Noni India - India noni (www.noni-india .com) States that that Noni is natural, nutritional and herbal food supplement giving amazing results.

Indian Noni (www. indian noni .net/faq/faq .htm). This site describes all about noni properties as well as Noni Drink as Herbal Dietary Supplement and benefits of regular use discussed stated above in this invention.

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