Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
  • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
  • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D307/62—Three oxygen atoms, e.g. ascorbic acid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/24—Heavy metals; Compounds thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/24—Heavy metals; Compounds thereof
  • A61K33/34—Copper; Compounds thereof

Definitions

• compositions for the treatment of cancer and colitis ulcerosa as well as the use of a titanium complex and a zinc salt for the preparation of the composition-
• the present invention relates to a composition
• a composition comprising a mixture of a complex of ascorbic acid, Ti 3+ and Cu 2+ with a Zn salt and optionally also with an Mn salt with a prophylactic, palliative or curative effect on diseases in human beings and animals, said diseases manifesting themselves as abnormal blood pictures in the persons or animals suffering therefrom, where the abnormal blood pictures reveal a reduced content of zinc, titanium and manganese.
• diseases are for instance cancer including leukaemia and colitis ulcerosa.
• the invention relates furthermore to the use of said mixture for the preparation of a composition with a prophylactic, palliative or curative effect on such diseases.
• cytostatica are chemical compounds effective on the cell division and with a drastic toxic effect.
• the treatment is prolonged and because of the toxicity attended with very serious side effects.
• the titanium complex it turned out that cases exist where the known tita- nium complex does not have an effect or only to an insufficient degree. Thus it turned out that when used alone the titanium complex is unable to prolong the life of A.K.R. mice genetically tending to suffer from malignant cancer diseases and which accordingly never live more than 14 months.
• the present invention relates to a composition of the above type which comprises a complex of 36 moles of ascorbic acid, 1 mole of Ti 3+ and 6 moles of Cu 2+ , and which is characterised by further comprising one or more zinc salts in an amount of 12 to 200 mg of zinc salt, preferably 30 to 100 mg, especially 45 to 70 mg, calculated as zinc per 600 mg of the complex.
• A.K.R. mice being mice spontaneously developing malignant diseases in form of leukaemia or tumours.
• Both the use of zinc alone and the use of the combination according to the invention of both the titanium complex and zinc, respectively, have resulted in an unprecedented survival.
• a treatment of A.K.R. mice being 10 to 11 months old at the beginning of the test revealed thus 20% and 31.4% , respectively, live mice 206 days after the beginning of the test, i.e. the mice were then approximately 17 months.
• composition according to the invention turned out to be efficient in the treatment of cancer.
• the composition according to the invention is, however, potentially applicable for the prophylaxis, alleviation or treatment of any type of disease causing an abnormal blood picture.
• diseases treatable with the composition according to the invention are cancer including leukaemia as well as colitis ulcerosa.
• composition according to the invention In support of the understanding of the effect of the composition according to the invention an illustration is provided below of the concentration of selected metals in the blood of a group of arbitrarily selected leukaemia patients compared with the concentration of the same metals in the blood of healthy (normal) persons.
• the numbers are average numbers for each group. 4
• Example 1 The following example shows that a complex of ascorbic acid, trivalent titanium and divalent copper as described in US-PS No. 4,211,712 has no effect in A.K.R. mice.
• the examples includes two test groups, viz. a test group and a control group.
• the test employed 140 days old A.K.R. mice.
• the test group included 50 A.K.R. mice which were administered 25 mg of titanium complex per kg of body weight in the daily portion of drinking water.
• the control group included 50 A.K.R. mice which received no composition.
• test results are shown in the following table 1 :
• the test employed 70 inbred female mice of the strain A.K.R./ABomf from Gl. Bomholtgard, DK-8680 Ry. At the beginning of the test the mice were 10 to 11 months old.
• the room temperature was 21 °C ⁇ 1 °C.
• the relative atmospheric humidity was 50 + 5 % .
• the air renewal was 14 times per hour, and the animals had light from 7.00 a.m. till 7.00 p.m.
• mice were divided by a random selection into two groups with 35 in each group. During the first 74 days all the animals of the test group were daily fed by gavage with 25 mg of titanium complex as well as 6 mg of zinc sulfate per kg of body weight. From day No. 75 till day No. 107 the test group was fed by gavage 5 days a week. Over the weekend the test group was fed with the composition, viz. the titanium complex and the zinc sulfate, through the drinking water. From day No. 108 till the end of the test period, i.e. till day No. 206, the test group was exclusively fed with the compositions through the drinking water.
• control group was treated in the same manner, but only with ZnSO 4 .
• the dosing was as follows:
• Test group 5 g of titanium complex + 1.2 g of ZnSO 4 were dissolved in 2000 ml of water.
• Control group Solution of 1.2 g ZnSO 4 in 2000 ml of water.
• the control group is administered ZnSO 4 .
• Table 2A shows also the death rate of A.K.R. mice administered a composition comprising a Ti-complex combined with ZnSO 4 compared with the death rate of A.K.R. mice administered ZnSO 4 alone (the control group). It appears from the table that at the end of the test, viz. on the 206th day after the beginning of the test, the death rate of the test group and the control group, respectively, was 68.6% and 80.0% , respectively. In other words, the titanium complex combined with ZnSO 4 has a stronger effect than ZnSO 4 alone as far as the chance of survival is concerned. At the end of the test, viz. on the 206th day after the begmning of the test, the test group included 11 live animals and the control group included 7 live animals.
• Table 2B shows the number of various symptoms of disease for the mice in the test group as well as for the mice in the control group.
• the test group included 5 cases of an enlarged 12 spleen whereas the control group included 15 cases of an enlarged spleen.
• leukaemia patients viz. both human and animal patients
• the titanium complex in combination with ZnSO 4 has a curative or prophylactic effect on leukaemia in A.K.R. mice, and that it is therefore also potentially applicable for a curative or prophylactic treatment of leukaemia in man.
• mice 11 mice (31.4%) were alive until the 206th day. After destruction the autopsy revealed:
• mice The spleen perhaps slightly enlarged; otherwise nothing abnormal.
• mice 7 mice (20%) were alive until the 206th day.
• mice (5.7%): None abnormal macroscopically .
• mice The spleen and thymus enlarged; otherwise nothing abnormal.
• mice revealed the following: 13 1 mouse: Small tumour in the spleen; otherwise nothing abnormal.
• Tests were performed on 70 6 months old A.K.R. mice, viz. 35 mice in the test group and 35 mice in the control group.
• the daily feed of the test group was admixed 5 ml of 1 % ascorbic acid + 2 drops of 15% Ti 2 (SO 4 ) 3 + 5 drops of approximately 30% CuSO 4 and 5 drops of approximately 30% ZnSO 4 .
• the control group received no composition.
• the results concerrning survival appear from table 3.
• a regeneration of cartilage after treatment with the composition according to the invention has been demonstrated in 2 patients from a group of 7 patients suffering from arthrosis and revealing a reduced content of titanium in the blood.
• a number of patients suffering from psoriasis including psoriasis arthritis and psoriasis pustulosa, were surprisingly found symptomless after treatment with the compo- 18 sition according to the invention.
• composition according to the invention must be considered suited for prophylaxis and treatment of diseases such as cancer, arthrose, rheumatic arthritis, psoriasis, psoriasis arthritis, psoriasis pustulosa, artherosclerose and ischaemic heart diseases.
• diseases such as cancer, arthrose, rheumatic arthritis, psoriasis, psoriasis arthritis, psoriasis pustulosa, artherosclerose and ischaemic heart diseases.
• composition according to the invention is usually administered orally in form of a powder or in form of tablets, but any other form of administration of the composition is potentially possible, such as for instance rectally.
• the normal daily dosis of the composition according to the invention is 175 mg to 1.5 g of titanium complex, preferably 675 to 900 mg of titanium complex in combination with 1 to 4 parts by weight of ZnSO 4 per 8 parts by weight of titanium complex.
• Tablets are produced in a conventional manner, each tablet comprising a homogenous mixture of the following ingredients:
• Tablets are produced in a conventional manner, each tablet comprising a homogenous mixture of the following ingredients:
• Tablets are produced in a conventional manner, each tablet comprising a homogenous mixture of the following ingredients:

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Inorganic Chemistry (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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• 1998
  • 1998-04-07 DK DK199800499A patent/DK173459B1/da not_active IP Right Cessation
• 1999
  • 1999-03-30 EP EP99911640A patent/EP1086090A1/de not_active Withdrawn
  • 1999-03-30 WO PCT/DK1999/000187 patent/WO1999051585A1/en not_active Application Discontinuation
  • 1999-03-30 AU AU30255/99A patent/AU3025599A/en not_active Abandoned

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