AU1996900A - Pharmaceutical preparation for treating viral infections - Google Patents

Description

WO 00/43025 PCT/IB00/00045 Pharmaceutical preparation for treating viral infections. FIELD OF INVENTION The present invention relates to a pharmaceutical preparation for treating viral infections. 5 More particularly, the invention relates to a pharmaceutical preparation for treating viral infections which also can be utilized as an immune stimulant. BACKGROUND TO INVENTION For many years immune deficiency and viral infection have been a great lo concern throughout the world. Immune deficiency is due to a failure of the body's immune system, which normally protects the body against infecting organisms and, for instance, the development of cancer. AIDS (acquired immune deficiency syndrome) and other immune deficiency disorders increase susceptibility to certain type of diseases, cancer and 5is recurrent or persistent infections. It is an object of the invention to suggest a novel pharmaceutical preparation for treating viral infections. SUMMARY OF INVENTION According to the invention, a pharmaceutical preparation for treating 20 viral infections includes powder derived from Vernonia Oligocephalus plant species. The preparation may include powder derived from aerial parts of Vernonia Oligocephalus plant species. CONFIRMATION

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2 WO 00/43025 PCT/IB00/00045 The preparation may be in powder form. Also according to the invention, a pharmaceutical preparation for treating viral infections includes an extract derived from Vernonia Oligocephalus plant species. 5 8a-(2-hydroxymethyl acryloyloxy)-hirsutinolide-13-0-acetate may be the extract derived from the Vernonia Oligocephalus plant species. The preparation may be in a tablet form. Each tablet may contain 50-800mg of the powder, e.g. 275mg of the powder. io The preparation may be in a capsule form. Each capsule may contain 50-800mg of the powder, e.g. 275mg of the powder. The preparation may be in an ointment form. The ointment may contain about 0.2-0.8g/ml, e.g. 0.4g/ml of the extract 15 incorporated in a cream base. The preparation may be in a tonic form. The tonic may contain about 0.1-0.8g/ml of the extract in about 30-80% alcohol. The tonic may contain about 0,2g/ml of the extract in about 40% alcohol.

3 WO 00/43025 PCT/IB00/00045 DETAILED DESCRIPTION OF PREPARATION OF PRODUCT AND TESTS CONDUCTED Preparation of product. The natural plant material, consisting of 100% dried aerial Vernonia 5 Oligocephalus, is dried and milled with a small hammer mill. Only the aerial parts of the plant are used. Thereafter the powder is used to prepare the following application forms: Capsules: White capsules, size "0". Approximately 500mg of dried powdered plant material per capsule. For oral 10 application. Cream: Tubes of 100ml each approximately 0.4g/ml incorporated into a cream base at 50:50 ratio. For topical application only. Tonic/tincture: 50ml bottles. Approximately 0.2g/ml in 40% alcohol. 15 For oral application only. The dosage for capsules (275mg of powdered plant material in each capsule) was that a capsule was taken 3 times per day, i.e. every 8 hours before or after meals. Tests had revealed no adverse effects in humans. 20 The treatment was administered orally to a patient with laboratory confirmed HIV infection (a male 46 years of age). When the first blood samples were taken, the patient had already been taking the extracts. The (CD8+) cell count, the (CD8+) cell percentage 4 WO 00/43025 PCT/IB00/00045 as well as the maintenance of the total lymphocyte count in accordance with the (CD8+) cell count and cell percentage are significant factors. The blood screening was taken initially and thereafter at regular intervals, the final screening taking place about one year after 5 commencement of the treatment. The results are as set out below: Blood screenings 1. T-LYMPHOCYTE SUBSETS NORMAL io Total lymphocyte count 2674 /cmm [1 000 - 4 000] Helper (CD4+) Cell count. 348 /cmm [600 - 1 500] Helper (CD4+) Cell percentage 13% [30 - 60] Suppr. (CD8+) Cell count. 1765 /cmm [400 - 1 000] Suppr. (CD8+) Cell percentage 66 % [22 - 51] 15 CD4+ : CD8+ ratio 0.2 [1.0 - 2.0] Viral load: Parameter Result: Reference Ranqe: HIV-1 viral load 8844 Not applicable 5 WO 00/43025 PCT/IB00/00045 Blood screening 2 T-LYMPHOCYTE SUBSETS NORMAL Total lymphocyte count 3120 /cmm [1 000 - 4 000] 5 Helper (CD4+) Cell count. 437 /cmm [600 - 1 500] Helper (CD4+) Cell percentage 14 % [30 - 60] Suppr. (CD8+) Cell count. 2122 /cmm [400 - 1 000] Suppr. (CD8+) Cell percentage 68 % [22 - 51] CD4+: CD8+ ratio 0.2 [1.0 - 2.0] io Viral load: Parameter Result: Reference Range: HIV-1 viral load 13780 Not applicable Blood screening 3 T-LYMPHOCYTE 15 SUBSETS NORMAL Total lymphocyte count 3438 /cmm [1 000 - 4 000] Helper (CD4+) Cell count. 447 /cmm [600 - 1 500] Helper (CD4+) Cell percentage 13% [30 - 60] Suppr. (CD8+) Cell count. 2303 /cmm [400 - 1 000] 20 Suppr. (CD8+) Cell percentage 67 % [22 - 51] CD4+ : CD8+ ratio 0.2 [1.0 - 2.0] Viral load: Parameter Result: Reference Range: HIV-1 viral load 17420 Not applicable 6 WO 00/43025 PCT/IB00/00045 Blood screening 4 T-LYMPHOCYTE SUBSETS NORMAL Total lymphocyte count 2804 /cmm [1 000 - 4 000] 5 Helper (CD4+) Cell count. 336 /cmm [600 - 1 500] Helper (CD4+) Cell percentage 12 % [30 - 60] Suppr. (CD8+) Cell count. 1738 /cmm [400 - 1 000] Suppr. (CD8+) Cell percentage 62 % [22 - 51] CD4+: CD8+ ratio 0.2 [1.0 - 2.0] 10 Viral load: Parameter Result: Reference Ranqe: HIV-1 viral load 3684 Not applicable Blood screening 5 T-LYMPHOCYTE 15 SUBSETS NORMAL Total lymphocyte count 3105 /cmm [1 000 - 4 000] Helper (CD4+) Cell count. 342 /cmm [600 - 1 500] Helper (CD4+) Cell percentage 11 % [30 - 60] Suppr. (CD8+) Cell count. 2111 /cmm [400 - 1 000] 20 Suppr. (CD8+) Cell percentage 68 % [22 - 51] CD4+ : CD8+ ratio 0.2 [1.0 - 2.0] Viral load: Parameter Result: Reference Rangqe: HIV-1 viral load 5716 Not applicable 25 7 WO 00/43025 PCT/IB00/00045 Blood screening 6 T-LYMPHOCYTE SUBSETS NORMAL Total lymphocyte count 3108 /cmm [1 000 - 4 000] 5 Helper (CD4+) Cell count. 342 /cmm [600 - 1 500] Helper (CD4+) Cell percentage 11 % [30 - 60] Suppr. (CD8+) Cell count. 2051 /cmm [400 - 1 000] Suppr. (CD8+) Cell percentage 66 % [22 - 51] CD4+ :CD8+ ratio 0.2 [1.0 - 2.0] l0 Viral load: Parameter Result: Reference Rangqe: HIV-1 viral load <500 Not applicable The above tests are summarized in the table below: Table I: test results HIV RNA CD4+ CD8+ TOTAL cell count cell count LYMPHOCYTES Reference Not applicable 600-1500 400-1000 1000-4000 Range Test 1 8844 348 1765 2674 Test 2 13780 437 2122 3120 Test 3 17420 447 2303 3438 Test 4 3684 336 1738 2804 Test 5 5716 342 2111 3105 Test 6 <500 342 2051 3108 15 Of particular importance is the drop in HIV RNA from 8844 to less than 500 over a period of a year.

8 WO 00/43025 PCT/IB00/00045 Also significant is the maintenance of CD4 counts and the increase in total lymphocytes. There is apparently very recent evidence that a sub set of CD8 cells are important in counteracting HIV infection. In this regard note that the CD8 absolute numbers also increased which 5 indicate that immune stimulation and metabolism are increased. It therefore is to be concluded that: * HIV RNA decreased progressively * CD4 remained stable * CD8 increased 10 * Total lymphocyte counts increased. Blood test results of patient Table II: Commencement 9 months later Tests Urea (1.4-8.6) 4.5 6.0 Calcium (2.1-2.57 2.52 2.52 Creatinine (40-110 90 95 Albumin(33-39) 38 43 Amylase(1-88) 45 48 Phosphorus(0.71-1.65) 0.81 1.12 Alk Phos(31-110) 70 74 ALT(SGPT) 6-43 36 19 AST(SGOT)(11-36) 42 34 Total billi(2-21) 9 9 CK(22-198) 187 141 LDH(53-234) 271 229 Glucose(3.9-6.4) 7.2 4.4 Triglycer(0.62-3.69) 4.96 3.75 Cholesterol(4.19-7.24) 5.38 5.25 LDL Choles Invalid high 2.83 triglycerides HDL Dex-s(0.78-1.66) 0.78 0.70 9 WO 00/43025 PCT/IB00/00045 Sodium (132-147) 139 136 Potassium(4.4-5.4) 4.4 4.5 Chloride(94-112) 101 99 RBC(4.5-6.4) 5.1 5.2 WBC(3.80-10.70) 10.6 9.46 HGB(127-181) 178 185 HCT(0.39-0.54) 0.52 0.56 MCV(79-96) 103 108 Neutrophil(1.96-7.23) 5.03 5.20 Lymphocyte(0.91-4.28) 3.70 3.22 Monocytes(0.12-0.92) 0.75 0.76 Eosinophil(0.00-0.57) 0.45 0.28 Basophils(0.00-0.20) 0.12 0.00 Platelets(140-400) 170 185 The above table shows no toxic effects while the patient was being treated. 1) Immune Stimulating and modulating properties discovered: The combination of the maintenance of the CD4+ cell count, the 5 decrease of HIV viral load, the increase in CD8+ cell count and the increase in the related total lymphocyte count and the lack of toxicity are considered to be of therapeutic benefit for the patient. 2) Anti-viral Activity: The viral load reduction results, which indicate anti-viral activities io against the HIV/AIDS virus, which was obtained from the above research trial are significant, considering that the pharmaceutical preparation applied is not concentrated or enhanced. Thus there is definite indications of antiviral activity present in pharmaceutical preparation according to the invention.

10 WO 00/43025 PCT/IB00/00045 Diseases and medical indications that can be treated It is concluded that the extract from the plant Vernonia Oligocephalus, can be used as an Immune Stimulant/Modulator to aid the body's immune system and used for treatment or assisting in the treatment for: 5 Common variable Immunodeficiency (CVID): CVID, which major features are: onset at any age, hypogammaglubulinemia with antibody deficiency, variable defects in cell-mediated immunity, clinical triad - infections, Autoimmune/inflammatory diseases, - Malignancy. io Etiology: CVID is immunologically heterogenous. Clinical Manifestations: CVID results in distinctive categories of disease complications including 1) acute and recurring bacterial infections, 2) Autoimmune disease, 3) 15 gastrointestinal disease, 4) granulomatous disease, 5) Cancer, 6) hepatitis. Infections: Infections associated with CVID: Recurrent Bronchitis, Sinusitis, Ototis, Conjunctivitis, Pneumonia, 20 Hepatitits, Meningitis, severe Herpes Zoster, Pneumocystis Carinii. Autoimmunity: The most common Autoimmune disease found in this patient population is Autoimmune Hemolytic Anemia, Idiopathic thrombocytopenic purpura, 11 WO 00/43025 PCT/IB00/00045 Rheumatoid arthritis, Sicca syndrome, Pernicious anemia, Crohn's disease, Ulcerative colitis, Sprue-like disease, Anti IgA antibodies, Alopecia totalis, Neutropenia, Juvenile rheumatoid arthritis, Primary biliary cirrhosis, Mixed connective tissue disease, Hyperthyroidism. 5 Cancer: Malignancies occur in patients with CVID. Type of cancer in CVID: Lymphoma, Hodgkin's disease, Adenocarcinoma of the colon, Adenocarcinoma of the stomach, Cancer of the tongue, Squamous-cell o10 carcinoma of the vagina, Adenocarcinoma of the ovary. Other Immunoglobulin Deficiencies: Transient hypogammaglobulinemia of infancy, Common variable immunodeficiency, X-linked ammaglobulinemia, IgG subclass deficiency, IgA deficiency. 15 HIV/AIDS virus infection: The spectrum of infections that affect HIV positive individuals often indicate a significant deficiency of CD4+ cells. The preparation in accordance with the invention assists the body's natural defense mechanism in protecting the immune system. 20 The product in accordance with the invention can be used for the treatment of viral diseases and the reduction of viral load due to the known anti-viral activities present in the extract.

12 WO 00/43025 PCT/IB00/00045 Diseases and disorders: Virus diseases: Arbovirus Infections, Chronic Fatigue Syndrome, DNA Virus Infections, Human Viral Hepatitis, Hepatitis B, other RNA Virus Infections, Viral Bronchiolitis, Viral Encephalitis, Viral Meningitis, Viral Pneumonia, Viral 5 Sexually transmitted diseases, Viral skin diseases, Viremia, Zoonoses, The following Genome type (viruses) can be treated with the aid of the preparation in accordance with the invention: DNA viruses: dsDNA viruses, ssDNA viruses. Reverse transcriptase RNA viruses: dsRNA viruses, (-)ssRNA viruses, (+)ssRNA viruses. io Unassigned viruses, Subviral Agents. Prions, Satellites, Viroids. General diseases: Anti-depressant, nervous conditions, alcoholism, liver diseases, general hepatitis, respiratory problems, pneumonia. General comments: 15 The active incredient in the Vernonia Oligocephalus plant species may be 8a-(2-hydroxymethyl acryloyloxy)-hirsutinolide-13-0-acetate. The Vernonia Oligocephalus is also known as Vernonia Oligocephalus (DC) Walp. and the widely used name Vernonia Kraussii Sch. Bip. must be accepted as a synonym thereof.

Claims (6)

1. A pharmaceutical preparation for treating viral infections including powder derived from Vernonia Oligocephalus plant species.

2. A preparation as claimed in claim 1, including powder derived 5 from aerial parts of Vernonia Oligocephalus plant species.

3. A preparation as claimed in claim 1 or claim 2, which is in powder form.

4. A pharmaceutical preparation for treating viral infections including an extract derived from Vernonia Oligocephalus plant species. 10 5. A preparation as claimed in claim 4, in which 8a-(2-hydroxymethyl acryloyloxy)-hirsutinolide-13-0-acetate is the extract derived from the Vernonia Oligocephalus plant species.

6. A preparation as claimed in any one of the preceding claims, which is in a tablet form. 15 7. A preparation as claimed in claim 6, in which each tablet contains

50-800mg of the powder. 8. A preparation as claimed in claim 7, in which each tablet contains 275mg of the powder. 9. A preparation as claimed in any one of claims 1 to 5, which is in a 20 capsule form. 10. A preparation as claimed in claim 9, in which each capsule contains 50-800mg of the powder. 14 WO 00/43025 PCT/IB00/00045 11. A preparation as claimed in claim 10, in which each capsule contains 275mg of the powder. 12. A preparation as claimed in any one of claims 1 to 5, which is in an ointment form. 5 13. A preparation as claimed in claim 12, in which the ointment contains about 0.2-0.8g/ml of the extract incorporated in a cream base. 14. A preparation as claimed in claim 13, in which the ointment contains about 0.4g/ml of the extract incorporated in a cream 10 base. 15. A preparation as claimed in any one of claims 1 to 5, which is in a tonic form. 16. A preparation as claimed in claim 15, in which the tonic contains about 0.1-0.8g/ml of the extract in about 30-80% alcohol. 15 17. A preparation as claimed in claim 16, in which the tonic contains about 0,2g/ml of the extract in about 40% alcohol.