OA11602A - Novel therapeutic antiviral compositions for the treatment of acquired immunodeficiency syndrome (AIDS) disease and its variants. - Google Patents

Description

The invention relates to novel antiviral compositions based on extracts of medicinal plants for the manufacture of virolysis, virostatic and viroextirpant medicaments for the treatment of Acquired Immunodeficiency Syndrome (AIDS) disease and its various variants. .

AIDS is an infectious disease that is hard on the whole planet and especially the African continent. It has been found that AIDS is often accompanied by lymphadenopathic syndromes (biliary lesions, pancreatic lesions, prolonged fever, infectious dermatoses, kaposi sarcoma) which in their final stage are manifested by a collapse of the subject's immune defenses. this pandemic has been isolated since 1983 by Professor LucMontagnier of the Institut Pasteur and identified under the name of LAV (Lymphadenopathy Associated Virus). The virus and its various variants was the subject of OAPI patent No. 08096 issued on August 31, 1986 on behalf of the Institut Pasteur. It is known that a virus of the same type as LAV has been identified in the US and referred to as HTL VIII (Science 1984 Vol 224 4648.497). The OAPI Patent No. 09043 issued to CRUZ Joseph on the 31/03/191 relates to new anviral compositions based on extract from the plant of Mimosa Pudica LINN for therapeutic use for the treatment of AIDS.All research on the virus seek to kill it within the host organism and not to extirpate it through the natural escape routes of the human body (stool, urine). Current antiretrovirals mutate the pathogen into more and more virulent.

For more than twenty years there has been a pandemic, research institutes, governmental and non-governmental organizations, United Nations agencies, in short, the entire Scientific, Political, Social, Cultural and Civil Society Community. is committed to the fight against HIV / AIDS. Further information is provided daily about the community's efforts to find either a vaccine or an antiviral, often with the support of the World Health Organization or other partners such as the Ford USA Foundation. The conventional approach of treatments in HIV infection by the use of antiviral substances such as azidothymidine (AZT), DDC, 3TC, FAZT / 3C, indinavir reduces plasma viral load at the level of the lowest and the longest possible time. The results, even if positive, remain limited. On average, 50% of patients have their plasma viral load drop to 50 copies / ml after about 12 months of treatment. But in the present state of affairs, the problems still unresolved by the use of antiretrovirals are still relevant, especially the impossibility of total eradication. Immune restoration is insignificant even when the CD4 lymphocyte count has greatly increased, the permanence of antiretroviral latoxicity has not yet been resolved. Other problems are still unresolved by the use of antiretrovirals, such as the risk of early development of antiretroviral resistance, the uncertainty as to the duration of maintenance of treatment efficacy. Stresses related to the use of current antiretrovirals should also be noted, as they require patients to take 20 or so drugs a day and their cost is very high compared to the purchasing power of the African populations who are most exposed to HIV. infection of HIV / AIDS. 1 011602

For a long time, men have always used plants as medicines, especially in Africa, Latin America, Asia, or the only unmet problems are dosage and ethnomedical analysis.

Increasingly, the international community is becoming aware of the need to involve healers in the prevention of HIV, and to use traditional medicine as well.

We know that the foundations of the First International Conference on Traditional Medicines and HIV / AIDS held in March 1999 in Dakar, showed the role that healers can play in the prevention, the management of opportunistic diseases, and in the search for a solution. therapy of this pandemic.

The work of an African NGO for the Promotion of Traditional Medicines (PROMETRA) on the involvement of healers in the treatment of HIV / AIDS has been the focus of many international scientific conferences (Yokohama Conference, Japan 1986, Washington DC USA 1996. 12 * "* International Conference on HIV / AIDS, Geneva 1998, Benin 1999: Lusaka 1999, Durban, July 2000, Cameroon 2000). The results of the researches obtained since 1989 by the Experimental Center of Traditional Medicine located in Fatick (Senegal), created by PROMETRA, focused on the plants used by healers.

The center has carried out a great deal of research on various diseases, mainly those considered incurable by conventional medicine. It should be noted that if the treatment is done by traditional plants, the controls of the patients are done by the most rigorous scientific methods, the most advanced current progress known

The new compositions which are the subject of the invention are based on extracts of plants ofMomordica balsamina, Aframomum melegueta, Cyperus articulatus, Ficusiteophylla and Tamarindus indica.

On the 5 plants selected in the invention, studies were carried out and allowed to show for each of them results.

The studies focused on the following aspects: - botanical - chemical - phamacological - clinical. 2 011602

I - STUDIES AND RESULTS

MOMORDICA BALSAMINA

Botanical

Herbaceous liana with slender stems creeping or climbing. The flowers are axillary; the 5 fruits are ovoid orange when mature, with many spines marrow non-pungent.

Chemistry

The leaves contain two acidic resins and a bitter substance, momordicin.They are rich in free C vitamins: 0.04 to 0.05% with or without carotene. It also contains aminobutyric acid which hinders evolution and renders the development of the virus static.

Pharmacology

Extracts of the whole plant give a hypoglycemic, anti-cancer action, the antibiotic activity of leaf extracts is proven.

The abortive proteins (momorcharines) possess, in vitro and in vivo, modulated actions on the immune system.

Momorcharins have an inhibitory action on the human immunodeficiency virus.

AFRAMOMUM MELEGUETA

Botany 20 Rhizomatous plants with upright stems, up to 1 m to 1.50 m tall.

Beautiful flower in spikes located on a peduncle coming out of ground; Red fruits.

Chemistry

Distillation produces essential oils containing caryophyllene, kayene, β-pinene, cineol, geraniol, geranyl acetate and terpineol. The seeds called maniguette contain 0.30% of a yellowish essence odoragrable, aromatic and a very bitter bitter principle: the neighbor paradol of gingerol.Son action polarizes the action of momorcharine by increasing the evolution of the mediuminhibant and neutralizing viral proliferation.

Pharmacology Aframomum are tenicidal purgatives and the decoction is used for baths in the case of deficiency edema. They have vermifugal properties from the roots. They play a big role in the treatment of rheumatism and pulmonary diseases. 3 011602

CYPERUS ARTICULATES

Botanical

Perennial herb, rhizomatous, cylindrical, upright stems up to 1.75 m high and 8 mm in diameter. Leaves reduced to seeds applied against the stem. 5 Flowers: parasols with irregular peduncles.

Chemistry Chemical analysis yielded sesquiterpenes and sesquiterpene alcohols with low odor. Cyperenone in the form of 2,4-dinnro phenylhydrazone was detected and named isopatchoulene -4. It makes it possible to remove the HIV virus from the different infected tissues by promoting its elimination by urine and faeces.

FICUS ITEOPHYLLA

Botanical

Medium tree 8 to 10 m tall with short, twisted trunk. Crown very spread, occasionally flattened. Bark light gray, smooth or partly scaly. The fruits are small, pubescent figs in pairs at the axils of the leaves.

Chemistry and pharmacology

The macerated bark is used as an antidysenteric and antirheumatic. Decocted root is used in the treatment of tuberculosis and mental disorders. It is an anti-anemic and an important fortifier.

20 TAMARINDUSINDICA

Botanical

Large tree 30 m high and one meter in diameter with large, spread crown. Barkgrise very cracked and scaly. Yellowish flowers in unstable clusters. Flowering from December to May. Fruit straight or slightly flattened curved, cylindrical. The pulp is very dark at maturity.

Chemistry

The fruit contains tartaric acid (8-18%), reducing sugars (25-41%), lapectin (2-35%), and proteins (2-3%). It plays an excipient role in composition of the product and allows to eliminate by the stool and urine HIV extracted by other drugs.

Pharmacology

Bactericidal properties, (1% pectin) and antifungal, laxative, regulator of the transitdigestive and moderate diuretic. 4 011602

Π - CLINICAL STUDIES

The novel compositions of extracts of Momordica balsamina, Afamomum melegueta, Cyperus articulants, Ficus iteophylla, Tamarindusindica plants have been administered to patients with Acquired Acquired Iramuno-Disability Syndrome, having the following conditions: ) Constitutional offenses often characterized by fever fatigue, night sweats, weight loss, loss of appetite (anorexia), general discomfort, c) lymphatic disorders marked by pain in adenopathies, e) Oral syndrome marked by wounds (foot-and-mouth ulcers) ) Painful and / or tender gums of lily of the valley (Candida's yeasts) Kaposi's sarcoma in the oral herpes bouchera an oral leukoplaque dura the red or sensitive tongue erythemaeusa rash or irritation lipsticks or nasal folds) Gastrointestinal disorders characterized by nausea vomiting (more one week) pain of bloating of swallowing pains: dysphagia of undigested food in stools of lack of appetite 40 diarrhea b) Skin syndrome marked by itching eruptions of dryness of Kaposile's sarcoma shingles (herpes zoster) l diagnosed fungal infection (mouth, buttocks, genitals, other) d) Eye disorders marked by changes in eye spots (floats) sensitivity to light (photophobia) f) Respiratory conditions characterized by coughing shortness of breath dysnea state nasal congestionone sinus congestion phlegma asthma painful breathing h) Genitourinary disorders with a suppuration of the penis or vagina a decrease of sexual urges ulcerations a genital worm (condyloma) genital herpes genital candidiasis or yeast increased menstrual periods (duration) spaniomémor rheeune increased bleeding during periods of menstrual bleeding bleeding or decreased bleeding during periods of menstrual periodsoligomenorrhea 5 i) Rectal disorders marked by warts rectal herpes of hemorrhoids sores or tears (cracks) bleeding from itching k) Neurological conditions characterized by pain headache loss of memory or weak memory numbness of hands and feet anxiety, splinters of seizures or convulsions, weakness of arms and / or legs of burning sensations and / or fainting cries 011602 j) Musculoskeletal disorders with pain in the joints a rigidity of the joints an inflammation of the articulations of the muscular pains a melting muscular 1) Psychological disorders characterized by an apathy or lack of interest of the changes of humor a depression The experimentation of the invention on people living with HIV / AIDS estdéroulée in two phases. A first phase spread over 10 years during which more than a hundred patients with medical records from hospitals in Dakar (Le Dantec, Principal, Frann) took extracts from the five medical plants provided by traditional healers in the Fatick area. The patient has observed an improvement, if not a complete cure, of the opportunistic diseases in the patients, since no relapse has occurred even after cessation.

The relationship of trust established by the applicant and the traditional healers of Benin, Senegal, Cameroon, Uganda and South Africa led him to rigorously study 10 patients over a period of 12 months. Taking these drugs did not reveal any side effects. On the contrary, the new composition produces several actions among which: a. an extirpating action of the HIV / AIDS virus by the natural evacuation routes of the body (urine-urine) b. curative action on other viral diseases such as shingles, viral hepatitis, measles and chicken pox, c. mild laxative, digestro-regulatory and diuretic action, d. a tonifying action of metabiolism, e. stimulation and augmentation of the reticuloendothelial system thereby increasing the patient's immune defense, f. an orexigenic action, g. an antipyretic and antidepressant effect.

The new compositions allow the extirpation of the pathogenic agent as mucosa glairo-sanguinolantes by the natural pathways of the body of the patients (stool, urine). The different affections of Acquired Immune Deficiency Syndrome have disappeared in patients. 6. 011602

ΙΠ - RESULTS OF THE CLINICAL TRIAL

Duration of clinical and paraclinical experimentation: 1 yearNumber of patients 10 patients were treated in the context of clinical and paraclinical experimentation.

Clinical evolution under the new composition

Clinical signs of patients before treatment SYMPTOMS / AFFECTION NUMBER OF CASES Hypotension 6 Hyperthermia, long-term fever 9 Severe asthenia 8 Nausea, vomiting 1 Dysphagia and oral ulcers 3 Chronic diarrhea 5 Diffused pain, muscle aches 6 Rebellious oh-cephalal headache 1 Depressive state 3 Zona 3 Thinning 9 Cervico-maxillary polyadenopathy 1 Chronic furunculosis 2 Anorexia 1 Vulvovagina + leucorrhea 1 ENT infection 2 Metrorrhagia 1 Anxiety 2 Pruritic dermatosis 1 Hepatitis 2 Paresthesia 1 7 011602

Evolution of the state of the patients after two months of treatment

Sym ptome / Affection Before treatment Number of cases Evolution noted at the end of May 2000 Total Aggra vation Stagnation Improvement Healing Hypotension 6 1 5 6 Hyperthermia, long-term fever 9 9 9 Deep asthenia 8 8 8 Nausea, vomiting 1 1 1 Dysphagia and Oropharyngeal Aphtises 3 3 3 Chronic diarrhea 5 5 5 Diffuse pain, stiffness 6 6 6 Reversing chronic headache 1 1 1 Depressive state 3 1 2 3 Shingles 3 3 3 Slimming 9 9 9 Cervico-maxillary polyadenopathy 1 1 1 Chronic furunculosis 2 2 2 Anorexia «1 1 1 Vulvovaginitis + leucorrhea 1 • 1 1 ENT infection 2 2 2 Metrorrhagia 1 1 1 Anxiety 2 2 2 Pruritic dermatosis 1 1 1 Hepatitis 2 2 2 Paraesthesia 1 1 1 8 011 602

Evolution of the patient's condition after six months of treatment

Symptom / Affection Before treatment Number of cases End-May 2000 change Total Aggra vation Stagnation Amphi ra-tion Healing Hypotension 6 6 6 Hyperthermia, long-term fever 9 9 9 Deep asthenia 8 8 8 Nausea, vomiting 1 1 1 Dysphagia and Oropharyngeal ulcers 3 3 3 Chronic diarrhea 5 5 5 Diffuse pain, stiffness 6 6 6 Reversing chronic headache 1 1 1 Depressive state 3 3 3 Shingles 3 3 3 Slimming 9 9 9 Cervico-maxillary polyadenopathy 1 1 1 Chronic furunculosis 2 2 2 Anorexia 1 • 1 1 Vulvovaginitis + leucorrhea 1 1 1 ENT infection 2 2 2 Metrorrhagia 1 1 1 Anxiety 2 2 2 Pruritic dermatosis 1 1 1 Hepatitis 2 2 2 Paraesthesia 1 1 1 9 011602

Evolution of the state of the patients after a weaning of six months of treatment

Symptom / Affection Before treatment Number of cases End-May 2000 change Total Aggravation Stagnation Improvement Healing Hypotension 6 6 6 Hyperthermia, long-term fever 9 9 9 Deep asthenia 8 8 8 Nausea, vomiting 1 1 1 Dysphagia and Oropharyngeal ulcers 3 3 3 Chronic diarrhea 5 5 5 Diffuse pain, stiffness 6 6 6 Reversing chronic headache 1 1 1 Depressive state 3 3 3 Shingles 3 3 3 Slimming 9 9 9 Cervico-maxillary polyadenopathy 1 1 1 Chronic furunculosis 2 2 2 Anorexia, 1 1 1 Vulvovaginitis + leucorrhoea 1 r 1 1 ENT infection 2 r 2 2 Metrorrhagia 1 1 1 Anxiety 2 2 2 Pruritic dermatosis 1 1 1 Hepatitis 2 2 2 Paraesthesia 1 1 1 10 011602

Paraclinical evolution

Viral loads of patients after two months of treatment under METRAFAIDS 10 N ° of record CV Month I CV month Π N ° 1 536496 268258 N ° 2 730337 181610 N ° 4 3429 2977 N ° 6 9462 872 N ° 7 183946 93225 N ° 9 231074 173533 No. 12 3052 908 No. 13 92907 - No. 15 88258 6998 No. 20 - -

CD4 counts of patients after two months of treatment 15 20 25 N ° of file CD4 months I CD4 months Π N ° 1 205 257 N ° 2 203 206 N ° 4 433 820 N ° 6 355 984 N ° 7 227 940 N ° 9 249 273 No. 12,342,596 No. 13,272,323 No. 15,301,414 No. 20-291 NB: Patients 13 and 20 were absent on certain days of sampling. The use of the novel compositions of medicinal plant extracts (Momordicabalsamina, Aframomum melegueta, Cyperus articulatus, Ficus iteophylla, Tamarindusindica) in the treatment of acquired immune deficiency states and in particular in HIV infection, extirpates pathogen. This element makes it possible to observe the absence of recurrences of opportunistic diseases several months after weaning. As a result, the drug increases the immune system and paves the way for a new vision of the drugs of the future. Seek to extirpate and not to kill.

The preparation of the medicaments containing plant extracts (Momordica balsamina, Aframomum melegueta, Cyperus articulatus, Ficus iteophylla, Tamarindus indica) is carried out according to different stages.

The preparation process is in several stages. - The whole plant of MOMORDICA BALSAMINA after collection is dried naturally and reduced to a fine powder 45 - The dry fruit of AFRAMOMUM MELEGUETA is also reduced to 11 011602 - fine powder. - After dissection, the root of the cyperus Articulatus is reduced to powderfine - The root of FICUS ITEOPHYLLA after natural drying is also reduced to fine powder - The fruit of TAMARINDUS INDICA is kneaded in a glass of water. Finally, all the powders as well as the dough resulting from mixing the fruit of TAMARINDUS INDICA are subjected to a mixture which, after drying, gives a new composition whose moisture content is practically nil. The weight of each proportion that enters the new composition is 5 g except for that of AFRAMOMUM MELEGUETA which is 2 g. Plant extracts are not associated with salts or with neurotropic vitamins in order to maintain their natural quality.

Pharmaceutical forms can be envisaged: naked or coated tablets, capsules, tablets scored or not, capsules.

The medicaments according to the invention can be used in the treatment of infections by opportunistic viruses (for example herpes virus, hepatitis virus, shingles). 12

Claims (5)

1. New antiviral compositions based on medecinal plant extracts ofMomordica balsamina, Aframomum melegueta, Cyperus articulatus, Ficusiteophylla, Tamarindus indica and their preparation for therapeutic use for the treatment of Immune Deficiency Syndrome disease Acquired (AIDS) and its variants 2. New compositions according to claim 1 characterized in that their method of manufacture is in 6 steps. at. The first is the removal of the whole plant Momordica balsamina, dried and reduced to a fine powder; b. The second is to reduce the dried fruit of Affamomummelegueta to a fine powder; c. The third is the desiccation of the root of Cyperus articulatus, which is then reduced to a fine powder; d. The fourth consists in reducing the root of Ficus iteophylla to a fine powder; e. The fifth is to knead the fruit of Tamarindus indica in 'Λ verred'eau; f. The sixth is to mix the whole in the result of the 5th stage 3. New compositions according to claims 1 to 2 characterized in that the extracts of the plants used are not associated with any substance including salts or neurotropic vitamins. 4. New compositions according to claims 1 to 3 characterized in that laconcentration and purification of the product are carried out according to conventional methods used in chemistry and biochemistry. 5. New compositions according to claims 1 to 4 characterized in that they are related to antigens of the AIDS virus. 13