EP1513546A1 - Compositions for therapeutic use comprising a vitamin, a metal salt and insulin or a growth hormone - Google Patents

Compositions for therapeutic use comprising a vitamin, a metal salt and insulin or a growth hormone

Info

Publication number
EP1513546A1
EP1513546A1 EP03735812A EP03735812A EP1513546A1 EP 1513546 A1 EP1513546 A1 EP 1513546A1 EP 03735812 A EP03735812 A EP 03735812A EP 03735812 A EP03735812 A EP 03735812A EP 1513546 A1 EP1513546 A1 EP 1513546A1
Authority
EP
European Patent Office
Prior art keywords
composition according
medicament
vitamin
insulin
therapy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP03735812A
Other languages
German (de)
English (en)
French (fr)
Inventor
Mishal Hamid Al-Sari
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Insignion Holdings Ltd
Veritron Ltd
Original Assignee
Insignion Holdings Ltd
Veritron Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Insignion Holdings Ltd, Veritron Ltd filed Critical Insignion Holdings Ltd
Publication of EP1513546A1 publication Critical patent/EP1513546A1/en
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • 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
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/27—Growth hormone [GH], i.e. somatotropin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
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    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • This invention relates to a composition comprising primarily natural products and to its use in therapy, especially of genetic disorders, viral diseases, cancer and AIDS.
  • the composition may also have cosmetic use.
  • Radiotherapy may be more localised, but is still dangerous to the patient and cannot avoid recurrence; the very localisation of the treatment means that there may be many cancerous or pre-cancerous cells that are unaffected by it, even if damage to healthy cells can be avoided.
  • Surgery, radiation treatment and chemotherapy all leave residual tumour tissue following the completion of therapy. Both radiotherapy and chemotherapy depress the immune system of the patient which can in turn reduce the effectiveness of any treatment.
  • Conditions of the type described above may be associated with a genetic disorder, e.g. some failure in the process whereby genes are translated into proteins, in vivo. It is known that a change of just one amino acid in a protein may be associated with disease, e.g. as in sickle cell anaemia. Proliferative conditions and cancer, among others, may be associated with an error in the sequence of events leading from organisation of genes to production of protein. Summary of the Invention
  • the present invention is based on the surprising discovery that the use of one or more natural products, i.e. materials that are present in the body in vivo or are at least well tolerated by it, are effective in the treatment of diseases of the type described above.
  • the nature of the materials is such that the novel medicament can be administered systemically, without causing major side-effects. Nevertheless, the effect of the medicament may be enhanced or supported by the use of certain further materials.
  • a medicament comprises one or more of the following components:
  • an effective agent for use in therapy may comprise only one of the given components (i),
  • the invention has, as an obj ect, the avoidance of gene mutation, and the prevention of rapid reproduction of mutated cells.
  • the effect of the components used in the present invention may be to regulate and/or correct the steps leading to expression of proteins, e.g. in immuno-compromised cells, in tumours or in cells that are otherwise acting abnormally.
  • a component such as component (i) "normalises” cells, possibly by correcting a differentiation gene or by activating a gene that lyses abnormal cells.
  • this component is provided in a form that can act on the affected cells. The possibility that cells are normalised would help explain why cells that are already normal remain unaffected, i.e. the absence of side- effects, and why use of the composition does not change cancer cells (as observed visually) but renders them benign, and why metastasis is inhibited.
  • component (i) may allow the cell or its components to function normally. Genes that are responsible for differentiation may be corrected or, if not corrected, a suicide gene is unmasked, and lyses tumour cells.
  • a genetic disorder may be introduced or a genetic abnormality may be present.
  • the present invention can prevent the virus from penetrating the cell membrane, or can destroy the virus. An abnormality in the membrane or receptor can be corrected.
  • a normalised cell is not susceptible to the virus which is then destroyed by phagocytosis, stimulated and enhanced by opsonisation.
  • the first of the given components of a composition of the invention is an antioxidant. The function of this component may be to prevent the formation of S-S bridges by oxidation of cysteine residues.
  • Disulfide linkages are caused by many oxidising agents, and cause loss of enzymatic activity.
  • the antioxidant may inhibit the production of oxygen radicals (free radicals) as a by-product of the normal metabolism of oxygen. These oxygen radicals are very damaging to cell membranes, proteins, lipids and DNA. Oxidative damage accumulates with age and is considered to be a major contributor to ageing and the development of degenerative diseases (e.g. cancer, cardiovascular disease, immune system decline, etc).
  • Suitable antioxidants for use in the invention are small molecules such as vitamin C, A and E. It will be appreciated that a suitable precursor of any such compound may be used, e.g. ⁇ -carotene.
  • the preferred antioxidant for use in this invention is vitamin C, e.g. as ascorbic acid.
  • a suitable dosage of this component is 1 to 500 mg/kg/day.
  • the first material that may be an essential component of a medicament according to the invention typically comprises one or more components of vitamin B.
  • Many enzymes catalyse reaction of their substrates only in the presence of a specific non-protein molecule, i.e. a coenzyme. Coenzymes frequently contain B vitamins as part of their structure.
  • vitamins B 1 thiamine hydrochloride
  • B2 riboflavin sodium phosphate
  • PP nicotinamide
  • B6 pyridoxine hydrochloride
  • B5 diexpanthenol
  • a second material that may be an essential component of a medicament according to the present invention is a metal salt that provides metal ions, in vivo.
  • the nature of the anion is not critical, and will generally be chosen to be non-toxic and of suitable solubility or other appropriate compatibility with other components of the medicament.
  • Many metal ions act as positive modifiers, and certain enzymes require the presence of metal ion for full activity.
  • the function of the metal ion may be to complement the coenzyme.
  • the ion may be, for example, Na, K or multivalent such as Fe, Mo, Mg, Mn, Ca, Zn, Cu or Co. This may be in the form of a salt, of which many examples are known, e.g.
  • the third material that may be an essential component of a medicament according to the invention may be an agent that increases the permeability of cell membranes or otherwise enhances transport, e.g. by action on receptors. This material may enhance the ability of the cells that need treatment to receive the other active material or materials that may be included in the novel medicament, especially in human therapy (it may not be required in veterinary medicine).
  • a preferred agent of this type is insulin or a growth hormone. A typical dosage of insulin is 1 to 1000 IU/kg/day.
  • the third material that may be an essential component of a medicament of the invention may also comprise an antihistamine.
  • Such a material can not only prevent or reduce abnormal reactions, especially allergic reaction, but also prevent the accumulation of substances which block transport, e.g. by binding to cell membrane receptors.
  • antihistamines work by competing with histamine released by mast cells and basophils for histamine receptors on the mucosa of the eyes, nose, bronchial airways and skin.
  • the antihistamine binds to the receptor and prevents histamine attachment, thereby blocking the effect of histamine in the tissues.
  • Antihistamine drugs counteract the physiological effects of histamine production, in allergic reactions and colds.
  • Antihistamines can be divided into classical and non-sedating antihistamines. There are many examples of such compounds, including acrivastine, azatadine, azelastine, brompheniramine, carbinoxamine, cetirizine, chlorpheniramine, clemastine fumarate, cyproheptadine, diphenhydramine, doxepin, hydroxyzine, fexofenadine, loratadine, meclizine, phenindamine, promethazine. pyrilamine and tripolidine.
  • a preferred material for use in the invention is chlorpheniramine maleate.
  • a suitable dosage of such a component is 0.1 to 50 mg/kg/day.
  • a medicament of the invention may comprise other components, depending on the intended effect, the nature of the formulation, the route of administration, and other factors that are known to those skilled in the art.
  • the medicament maybe formulated in water, e.g. to provide an aqueous solution or suspension suitable for injection. It may be desirable to include in any such formulation one or more additional substances that aid dissolution or suspension of active components, such as an organic or a polar solvent.
  • the composition may comprise conventional excipients, for example, phenol (which acts as a preservative).
  • an anti-irritant It may be desirable to include an anti-irritant. It has been found that these effects can both be provided by the use of natural substances, e.g. the dried flower heads of the composite plant Matricaria chamomile or one or more materials therein, including volatile oils, azolene, anthemic acid, apogenin, glycosides and other substances.
  • Azolene has antiphlogistic properties, abates allergic reactions, and intensifies regenerative processes.
  • Apigenin (4',5,7-trihydroxyflavone) has a strong spasmolytic effect. Flavones reverse capillary fragility; such a component can inhibit abnormal chemical transmitters.
  • compositions of the invention can be formulated by methods known to those skilled in the art.
  • Pharmaceutically acceptable components should be used.
  • pharmaceutically acceptable refers to those properties and/or substances which are acceptable to the patient from a pharmacological/toxicological point of view and to the manufacturing pharmaceutical chemist from a physical/chemical point of view regarding factors such as formulation, stability, patient acceptance and bioavailability.
  • the pharmaceutical composition containing the active ingredient maybe in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs.
  • Such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavouring agents, colouring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations.
  • Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients such as, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example corn starch or alginic acid; binding agents, for example starch, gelatin or acacia; and lubricating agents, for example magnesium stearate, stearic acid or talc.
  • the tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastointestinal tract and thereby provide a sustained action over a longer period.
  • a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated, to form osmotic therapeutic tablets for control release.
  • Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.
  • Aqueous suspensions may contain the active materials in admixture with suitable excipients.
  • excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents, for example a naturally occurring phosphatide such as lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol, such as a polyoxyethylene with partial esters derived from fatty acids and hexitol anhydrides, for example polyoxyethylene sorbitan monooleate.
  • suspending agents for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethyl
  • Aqueous suspensions may also contain one or more preservatives, for example ethyl or n-propyl p-hydroxybenzoate, one or more colouring agents, one or more flavouring agents, and one or more sweetening agents, such as sucrose or saccharin.
  • preservatives for example ethyl or n-propyl p-hydroxybenzoate
  • colouring agents for example ethyl or n-propyl p-hydroxybenzoate
  • flavouring agents such as sucrose or saccharin.
  • sweetening agents such as sucrose or saccharin.
  • Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin.
  • the oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol.
  • Sweetening agents such as those set forth above
  • flavouring agents may be added to provide a palatable oral preparation.
  • These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid.
  • Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives.
  • a dispersing or wetting agent e.g., glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerin, glycerin, glycerin, glycerin, glycerin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, sorbitol
  • the pharmaceutical compositions of the invention may also be in the form of oil-in- water emulsions.
  • the oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures of these.
  • Suitable emulsifying agents may be naturally occurring gums, for example gum acacia or gum tragacanth, naturally occurring phosphatides, for example soya bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitan monooleate and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate.
  • the emulsions may also contain sweetening and flavouring agents.
  • Syrups and elixirs maybe formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and flavouring and colouring agents.
  • the pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated using suitable dispersing or wetting agents and suspending agents, examples of which have been mentioned above.
  • a sterile injectable preparation may also be in a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1,3-butanediol.
  • Suitable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium.
  • any bland fixed oil may be employed including synthetic mono- or diglycerides.
  • fatty acids such as oleic acid find use in the preparation of injectables. ⁇
  • compositions may also be administered in the form of suppositories for rectal administration of the drug.
  • Such compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
  • suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
  • suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
  • Such materials are cocoa butter and polyethylene glycols.
  • compositions are in the form of, for example, creams, ointments, jellies, solutions or suspensions.
  • topical application includes mouth washes and gargles.
  • composition of the invention may be given by injection. Intramuscular injection is preferred, although any parenteral administration is suitable.
  • the composition is given orally.
  • insulin should not be included in an oral formulation.
  • Oral administration may be particularly preferred for veterinary medicine.
  • Other active materials may also be given to the subject.
  • steroids and vitamins typically given orally, can support or enhance the effect of the medicament.
  • Suitable steroid hormones may increase the synthesis of specific proteins, by unmasking certain cistrons, with the assistance of essential metabolites such as vitamins and amino acids.
  • suitable steroids are estradiol, nandrolone and estriol.
  • Vitamins such as A, D and/or E may also be given. The function of vitamin A may be to preserve the integrity of epithelial tissue, to play a role in protein synthesis, and to stabilise cell membranes and also subcellular membranes.
  • a composition of the invention may have cosmetic use, since it has been found that, when used as a medicament, hair growth can be restored or induced.
  • a topical composition may be preferred.
  • compositions according to the invention involve the treatment (and possibly also the prevention) of conditions described above. These and others include topical conditions such as psoriasis, scleroderma and pemphigus, infectious bronchitis, cancers including sarcomas (such as Kaposi's sarcoma), leukemia, skin cancer and the carcinomas whose treatment is specifically illustrated below, as well as AIDS.
  • topical conditions such as psoriasis, scleroderma and pemphigus, infectious bronchitis, cancers including sarcomas (such as Kaposi's sarcoma), leukemia, skin cancer and the carcinomas whose treatment is specifically illustrated below, as well as AIDS.
  • the composition may be supplemented by the administration of a growth hormone. More generally, it may be used for therapy of proliferative and viral conditions, especially those associated with DNA or RNA viruses.
  • the action on RNA viruses may be direct, while the action on DNA viruses and cancer at least may
  • the medicament may also be useful in therapy of other genetic disorders such as motor neurone disease and multiple sclerosis.
  • the medicament may promote the patient's quality of life, without necessarily reducing tumour size. For example, it facilitates a healing process that has the following stages:
  • the medicament affects the immune system indirectly, by normalising body cells. It apparently has both direct and indirect effects in its anti-viral activity, demonstrated by its very rapid direct action on RNA viruses and by its direct and indirect action on DNA viruses and cancers. It apparently normalises otherwise abnormal genetic material; the effect may be both chemical and functional. It also appears that most of the cellular components become targets of the medicament, especially cell surface receptors and genetic material. Despite the effect on cells, no adverse side-effects have been detected, even after treatment for more than 18 months in cancer patients.
  • the patient may have the human retrovirus (HRV); this indicates human immunodeficiency virus type I, or strains thereof apparent to one skilled in the art, which belong to the same viral families and which create similar physiological effects in humans as various human retroviruses.
  • HRV human retrovirus
  • Patients to be treated include those individuals (1) infected with one or more strains of a human retrovirus, as determined by the presence of either measurable viral antibody or antigen in the serum, and (2) having either a symptomatic AIDS-defining infection such as (a) disseminated histoplasmosis, (b) isopsoriasis, (c) bronchial and pulmonary candidiasis including pneumocystic pneumonia, (d) non-Hodgkin's lymphoma or (e) Kaposi's sarcoma or having an absolute CD4 lymphocyte count of less than 200/mm 3 in the peripheral blood. Patients who are HIN-positive but asymptomatic would typically be treated with lower doses. ARC (AIDS-related complex) and AIDS patients would typically be treated with higher doses.
  • a AIDS-defining infection such as (a) disseminated histoplasmosis, (b) isopsoriasis, (c) bronchial and pulmonary candidiasis including pneumo
  • components used in this invention can be administered in conjunction with (or simultaneously, concomitantly or sequentially with) other antiviral agents such as AZT, ddl, ddC, 3TC, d4T or non-nucleoside anti-AIDS agents.
  • other antiviral agents such as AZT, ddl, ddC, 3TC, d4T or non-nucleoside anti-AIDS agents.
  • Treatment of AIDS refers to inhibition of the FUN virus and will vary, depending on the infected individual.
  • the medicament may delay or prevent the onset of symptoms.
  • the medicament may delay or prevent the onset of "full-blown AIDS”.
  • the medicament may at least considerably extend the survival time of these individuals.
  • the medicament can also be used to treat other viral conditions.
  • the virus may be a coronavirus, as in the case of SARS (severe acute respiratory syndrome). Further, as indicated above, it may have utility in veterinary medicine, e.g. in fowl's diseases such as Newcastle disease and fowlpox.
  • Example 1 - Medicament
  • Vitamin B2 riboflavin sodium phosphate 683.75 mg
  • Vitamin PP (nicotinamide) 5000 mg
  • Vitamin B6 pyridoxine hydrochloride 500 mg
  • Vitamin B5 diexpanthenol
  • the dried flower heads of the composite plant Matricaria chamomile were washed thoroughly with cold pyrogen-free distilled water.
  • the washed flower heads were added to the water in the beaker and heated and stirred until the temperature reached 95 °C.
  • the resultant medicament was poured into small vials or ampoules of 5.0 ml or large vials or bottles of 100 ml or 50 ml of the type used for intravenous fluids. This medicament was suitable for use as an injectable.
  • a preferred process for preparing a camomile extract is as follows:
  • Camomile flowers of suitable quality i.e. not too dry, are gently pressed through a 850 mm screen to remove dust and pick out green leaves. After discarding dust and particles, the flower heads retained by the screen are rubbed between the hands to release the yellow particles from the heads. The particles are then passed through a 850 mm screen to remove large bits of unwanted flower heads, and screened again three times through a 850 mm screen, shaking vigorously from side to side, to leave behind the lighter unwanted fraction. The resulting fraction is yellow in colour and slightly shiny. To 100 g of the fraction is added approximately 2 litres of pyrogen-free sterile water for injection in a 3 -litre clean glass beaker, and mixed by stirring.
  • the product is heated using a hot plate to 95 °C, then alllowed to cool to approximately 35 °C.
  • the extraction mixture is sieved through a 355 mm screen to remove particles.
  • the filtrate is passed through a 0.2 ⁇ m sterile filter, to give the desired liquid camomile extract.
  • the medicament described above was given as a 5 ml dosage, intramuscularly, twice daily (5 ml every 12 hours) for an average body weight of 75 kilograms (subjects 50-100 kg body weight).
  • the dose can be calculated, according to the body weight, as 0.072 ml/kg body weight twice daily.
  • Estradiol (5 mg) and Vitamin A (40000 IU) were given separately every week.
  • estriol 0.5 mg was given separately to the patient every day.
  • nandrolone decanoate (Deca durabolin) (25 mg) was given separately to the patient every 20 days. In various healthy animal and human models, this regimen has proved to be safe.
  • SSPE subacute sclerosing panencephalitis
  • Specific patients that have been treated are 10 independent patients having the following conditions: (1) adenocarcinoma of the head of the pancreas with metastasis to the regional lymph nodes and also to the liver, with a large cyst in the body of the pancreas (100 x 125 mm); metastasis to most of the skeletal regions; exudative moist scales all over the skin, diagnosed as eczema herpetica; ascites. (2) follicular carcinoma of the thyroid with metastasis to the right iliac bone; following treatment, the metastasis increased to include greater trochanter of the right thigh, the skull and other parts of the skeleton including the left vertebrae. (3) poorly differentiated squamous cell carcinoma of the mandible.
  • cerebella astrocytoma (a well differentiated low grade cerebella astrocytoma, histologically grade 1-2).
  • carcinoma of the head of the pancreas with multiple metastasis in the port a hepatis with obstruction of the biliary ducts intra- and extra-hepatic.
  • the patient was male, 41 years old. According to the medical report of his surgeon, the patient presented to him with a history of obstructive jaundice with progressive weight loss, oedema of the legs, palpable gall bladder and ascitis with ascitic fluid. Ultrasound examination showed enlarged liver with dilated intra- and extra-hepatic bile ducts in addition to the gall bladder.
  • the patient was operated on, and the findings were: advance carcinoma of the head of the pancreas, 50-75 mm in diameter, a large pancreatic cyst about 100-125 mm in diameter with secondaries in the regional lymph nodes, and a mass of 20 x 20 mm located in the inferior surface of the right lobe of the liver with dilated gall bladder and biliary ducts.
  • Palliative procedures were carried out (side-to-side choledochoduodenostomy around T-tube splint and retrocolic gastrojejunostomy).
  • the pathological report of the lymph nodes was metastatic adenocarcinoma.
  • the patient was an 8 year old male child, diagnosed as having a tumour in the occipital region of the brain.
  • the tumour was excised and examined histopathologically; it was a well differentiated low grade cerebellar astrocytoma, histologically grade 1-2. After excision of the tumour, an intra-cranial catheter was introduced in the intraventricular space for drainage. The patient was then discharged and given deep X-ray therapy, but his general health deteriorated. Death was anticipated.
  • the patient was a woman, 45 years old. She underwent operation of the osteolytic lesions which were found in the radiographs at the right iliac bone just above the acetabulum. Histopathological examination of a sample taken from the lesion showed a metastatic follicular carcinoma in the bone consistent with an origin in thyroid gland. The patient was treated by iodine radiotherapy, but metastatic lesions appeared in the greater trochanter of the right femur and then in the skull. Thyroidectomy found no primary lesion. It was concluded that the primary lesion was occulted.
  • Example D A male patient, 62, noticed increased mobility of the incisors of the lower j aw with swelling in the gum. Following consultation, he underwent complete extraction of his teeth from both jaws. A biopsy, done from tissues of the swelling in the incisors' region, examined histopathologically, showed a poorly differentiated squamous cell carcinoma. It was decided to remove the mandible of the lower jaw as, radiologically, multiple osteolytic lesions were found all over the bone. The patient refused insertion of an artificial (platinum) mandible.
  • the first patient exhibited persistent generalised lymphadenopathy (PGL) of many years' standing; severe weight loss; chronic blood diarrhoea of 10 years' history of remission and exacerbation which started due to ulcerative colitis; severe fatigue which rendered him unable to walk for several metres; and marked oral and lingual thrush (candidal stomatitis) with some papules at the cheeks which accompanied by severe symptoms of oesophageal candidiasus such as dysphagia.
  • PDL generalised lymphadenopathy
  • Retrovir as an antiviral drug, other antiviral drugs and many antibiotics. He gained some benefits from the antiviral drugs for a short period. A relapse in his general health occurred during such treatment.
  • the second patient exhibited: PGL of a few years' duration; chronic serosanguineous-like urethral discharge; herpes zoster infection (shingles) of the penis, leading to huge lesions and to fistula formation; decrease in libido; and poor psychological state.
  • the third patient exhibited: breathlessness (some difficulties in breathing); fatigue; and a chronic abscess at the right side of the nose, over the lacrimal duct, 10 mm below the medial angle of the right eye. This abscess was not dissolved or cured by local and general usage of antibiotics and local antiseptics.
  • lymph nodes did not dissolve completely, but their size was reduced to about one-third, and they became soft instead of rubbery, and mobile instead of fixed to the underlying tissues.
  • the fingernails that had deteriorated had not completely returned to normal, but new growth was free from fungal infection.
  • the neutrophils/lymphocytes ratio before treatment was 1:2. This ratio was monitored during the treatment; the ratio in the three patients became 2:1 which is almost the acceptable ratio.
  • Immunoglobulins especially IgG and IgA, also decreased to their normal ranges.
  • Antibody Serum Level HTV antibody serum levels were assayed in the three patients, at different dates.
  • the threshold value (relative fluorescent value) of the patients decreased successively, as follows:
  • RT-PCR was used to investigate blood samples taken from the three patients just before the treatment and at many times thereafter. After 70 days of treatment, HIV bands were detected at the same location of
  • HIN-1 positive control bands In one of the patients, the results showed a huge decrease in the viral RNA concentration to a very low level, at which its band could hardly be seen.
  • tumour stem cell assay In a tumour stem cell assay, the medicament inhibited growth of explanted human tumour cells in a concentration-dependent fashion (mean IC70: 1.6 vol%). Selectivity was demonstrated for lung, breast and melanoma cancer, corroborating the results from the proliferation inhibition assay. Furthermore, significant growth inhibition was found for 2/3 pancreatic, 1/2 gastric and 1/4 colon tumours.

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EP03735812A 2002-05-29 2003-05-27 Compositions for therapeutic use comprising a vitamin, a metal salt and insulin or a growth hormone Ceased EP1513546A1 (en)

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GBGB0212405.5A GB0212405D0 (en) 2002-05-29 2002-05-29 Composition and its therapeutic use
GB0212405 2002-05-29
PCT/GB2003/002295 WO2003101479A1 (en) 2002-05-29 2003-05-27 Compositions for therapeutic use comprising a vitamin, a metal salt and insulin or a growth hormone

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GB0501654D0 (en) * 2005-01-26 2005-03-02 Veritron Ltd Stabilised plant extract
GB0523257D0 (en) * 2005-11-15 2005-12-21 Veritron Ltd Purification process
GB0710536D0 (en) 2007-06-01 2007-07-11 Veritron Ltd Plant extract and its therapeutic use
DE102007030103A1 (de) * 2007-06-28 2009-01-02 Bode Chemie Gmbh & Co. Kg Verwendung einer synergistischen Zusammensetzung als therapeutisches oder kosmetisches Mittel
GB0808974D0 (en) * 2008-05-16 2008-06-25 Veritron Ltd Plant extract and its therapeutic use
EP2420228A1 (en) 2010-08-05 2012-02-22 Alpinia Laudanum Institute Of Phytopharmaceutical Sciences AG Composition comprising retinol, a precursor or a reaction product of it and a plant extract from at least one chamomilla plant for the treatment of cancer
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CN104302670A (zh) 2012-02-07 2015-01-21 Phi生物医药股份有限公司 制造用于经皮给药的透明质酸-蛋白结合体的方法以及由该方法制造的用于经皮给药的透明质酸-蛋白结合体
CN110496099B (zh) 2013-09-11 2022-06-21 伊戈尔生物药品股份有限公司 包含粘度降低剂的液体蛋白质制剂
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AU2003204391B2 (en) 2005-08-04
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GB0212405D0 (en) 2002-07-10
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EP1366768A1 (en) 2003-12-03
AU2003204391A1 (en) 2003-12-18
IS7578A (is) 2004-12-01
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ZA200409551B (en) 2005-10-11
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SM200300009B (it) 2004-12-01
ATE468134T1 (de) 2010-06-15
GB2392618A (en) 2004-03-10
RS102304A (xx) 2006-12-15
MXPA04011794A (es) 2005-07-05
UY27827A1 (es) 2003-12-31
BR0311371A (pt) 2005-04-05
GB2392618B (en) 2007-02-21
OA12862A (en) 2006-09-15
ECSP045458A (es) 2005-05-30
SM200300009A (it) 2004-12-01
GB2427824A (en) 2007-01-10
DE60332578D1 (de) 2010-07-01
AU2007203159A1 (en) 2007-07-26
MA27207A1 (fr) 2005-01-03
AU2007203159B2 (en) 2009-03-26
GB0325839D0 (en) 2003-12-10
TNSN04235A1 (en) 2007-03-12
WO2003101479A1 (en) 2003-12-11
ZA200210316B (en) 2003-07-04
GB0615918D0 (en) 2006-09-20
CN1466994A (zh) 2004-01-14
PL374199A1 (en) 2005-10-03
MEP22908A (en) 2010-06-10
AR039895A1 (es) 2005-03-09
AU2003236893A1 (en) 2003-12-19
CN1655811A (zh) 2005-08-17
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CA2487678A1 (en) 2003-12-11
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