WO1987002244A1 - Tissue growth regulation - Google Patents

Tissue growth regulation Download PDF

Info

Publication number
WO1987002244A1
WO1987002244A1 PCT/GB1986/000607 GB8600607W WO8702244A1 WO 1987002244 A1 WO1987002244 A1 WO 1987002244A1 GB 8600607 W GB8600607 W GB 8600607W WO 8702244 A1 WO8702244 A1 WO 8702244A1
Authority
WO
WIPO (PCT)
Prior art keywords
solution
biotin
preparation
temperature
tissue growth
Prior art date
Application number
PCT/GB1986/000607
Other languages
English (en)
French (fr)
Inventor
Neil Geddes Clarkson Hendry
Original Assignee
Neil Geddes Clarkson Hendry
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 Neil Geddes Clarkson Hendry filed Critical Neil Geddes Clarkson Hendry
Priority to IN896/DEL/86A priority Critical patent/IN168295B/en
Publication of WO1987002244A1 publication Critical patent/WO1987002244A1/en

Links

Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms

Definitions

  • This invention relates to a preparation for tissue growth control in humans or animals. More particularly, the invention relates to a group of physiologically active preparations, at least one member of which promotes, whilst the others inhibit, the growth of both normal and abnormal tissue.
  • the preparations of this invention provide for ( a ) the enhancement of normal tissue growth to accelerate normal repair functions and (b) the suppression of undesirable tissue growth, whether benign as in the fibrosis associated with excessive scar tissue formation, or aberrant, as in cancerous or other malignant change.
  • Background Art Extensive work has been done on the control of growth in plants, none of which is applicable to animal tissue.
  • G l cy l-hi sti d I-l si ne and pituitary growth hormone are two chemically characterised pure substances with an influence on growth, the former in the culture of isolated liver cells and the latter in bodily growth as a whole. None of these "growth factors" has been recorded as having any known usefulness in tissue repair, and are on the whole remote from the preparations to be disclosed hereinafter.
  • Cortisone and its derivatives are effective in the control of excess fibrous tissue formation such as may occur in some types of injury, in many cases of burns, and after some inflammatory diseases of the joints.
  • use of cortisone involves a considerable risk of side effects.
  • N-acetyl-D-glucosaminidase was closely related to what might be termed the "reactivity" of a variety of disease processes. This relationship existed under such a wide range of circumstances as to suggest a more important role than was then known for N-acetyl-D- glucosamine (NAG) and perhaps for other N-acetyl-0- glycosamines.
  • N-acetyl-D-glucosamine (2-acetamido-2-deoxy-D- glucose) residues are widely present in bound form in nature as is D-ga lactosamine .
  • NAG in a study of cell growth. Experiments relating to use of NAG are mentioned.
  • NAG dimer di-N-acetylchitobiose bound to a protein carrier in an attempt to preimmunise mice against the lethal effects of a transplanted tumour with limited success.
  • NAG residues onovalent lectin to cover the surface agglutination sites
  • the inventor arrived at this invention by carrying out investigations into the possibility that N-acetyl-D- glycosamines and their oligomers and derivatives of both classes of compound might play important, and previously unrecognised parts in the processes of healing and repair, and in the invasiveness and proliferation of malignant cells.
  • the present inventor provides a preparation for tissue growth regulation comprising
  • a divalent metal cation such as Hg, Ca or Hn together with a pharmaceutically acceptable anion.
  • the component ( a) of the preparation of this invention is N-acetyl-D-glucosamine or its oligomers or their completely or partially deacetylated derivatives.
  • the preparation is prepared as an aqueous solution containing N-acety l-D-g lucosamine,
  • the solution may include buffer salts.
  • the preparation is suitable for parenteral or oral administration.
  • the preparation of this invention may be made in a solid form for oral or rectal administration by formulation of a tablet, lozenge or suppository. Alternatively, it may be made as a powder to be taken, or formulated as an encapsulated solution or emulsion for oral administration or subsequent formulation and ad inistrat on as an injection solution. Further, it can be formulated for topical application in a suitable neutral ointment base.
  • the method of making the preparation affects the properties thereof. For example, mixtures may be activated by subjecting them to varying periods of, and conditions of, heating and of drying or partial drying, leading to the intermediate recovery of crystalline and associated insoluble materials, with other materials remaining in solution or in a syrupy form.
  • the inhibition can be made to be either competitive or non-competitive.
  • the preparation can influence the total level of N-acetyl- D-g lucosami ni dase activity in the body and also alter the proportional effect of the two main isoenzymes. In doing this, the preparation appears to mimic the reactions of the body to many disease processes as, for example, in its response to foreign tissue rejection, to inflammation and to malignancy.
  • N-acetyl-D-glucosamine itself has been shown to have a stimulating effect upon defence cells in the body, and it is believed that the preparation of this invention provides a new and selective means of influencing the body's immune mechanisms.
  • the active components may be administered by mouth or by injection, either alone, or incorporated in physiologically-benign fluids or solids or any other pharmaceutically acceptable vehicles, carriers and adjuvants. Whilst not wishing to be bound by any particular theory, the role of the active components may be selectively to block or unblock active sites in enzymes part cipating in tissue or cell growth. There may be action on cell surface sites responsible for functions such as cell specificity, or the transfer of nutrients and hormones.
  • the present invention finds a use in (a) the control of the proliferation, growth and invasiveness of malignant cells; ( b) the regulation of the level of activity of cells involved in the repair of tissue after injury or inflammation, with the ob ective of encouraging healing whilst, at the same time, controlling any tendency for one aspect of healing to outstrip the other, as, for example, the over-production of collagen by fibroblasts results in hypertrophic scar formation, with consequent cosmetic or functional impairment; and (c ) the stimulation of healing where it is indolent as, for instance, in the elderly or in those others having suffered very severe infections.
  • Example 1 A method of preparing (a) a preparation for use in the stimulation of healing and (b) a preparation for the control of malignant cells.
  • (a) 3.23 g of N-acetyl-D-glucosam ne, 200 mg of biotin, 375 mg potassium dihydrogen phosphate, and 1.8 g of magnesium sulphate were dissolved in water to give 100 ml of solution, which was maintained at 55°C in a closed vessel for 72 hours. The contents were then cooled and kept at just above freezing point. During the next 24 hours a mainly crystalline deposit separated. This was removed by cent r fugat ion and the solid deposit was washed with water (or ethanol).
  • the solid had no significant inhibitory power on N-acet l-D-g lucosami ni dase, but had a powerful enhancing action on its B-i so-enzyme .
  • the solid was insoluble in water, but soluble in lipids. Following treatment of patients with areas of indolent healing using the solid, rapid regeneration of skin cells was observed. Therefore, the aforementioned steps provide a means of stimulating healing.
  • Example 2 A method of preparing a preparation for regulating the level of activity of cells involved in the repair of tissues following injury or i nf lammat i on .
  • 3.2 g of N-acetyl-D-glucosamine, 10 mg of biotin, 375 mg of potassium dihydrogen phosphate and 1.8 g of magnesium sulphate were dissolved in water to provide 100 ml of solution which was placed in a closed vessel and maintained at a temperature of 70-80 C for 72 hours. The resulting solution was cooled and freeze-dried.
  • the material resulting from this showed non-competiti e specific inhibition of the A isozyme of N-acetyl-D- g lucosami ni dase and a varying degree of competitive inhibition only of the B isozyme.
  • Addition of the material to cultures of fibroblasts produced a dose- related inhibition of fibroblast proliferation about 50% without causing cell death.
  • it has been adm-ini stered on 47 occasions to 35 horses suffering mostly from injuries to the deep flexor tendon of the fore-limb, a condition frequently resulting in permanent disability, sometimes to a degree necess tating slaughter. All 35 horses returned to competition, usually at pre- injury level of soundness.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/GB1986/000607 1985-10-08 1986-10-08 Tissue growth regulation WO1987002244A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
IN896/DEL/86A IN168295B (cs) 1985-10-08 1986-10-08

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB858524807A GB8524807D0 (en) 1985-10-08 1985-10-08 Tissue growth regulation
GB8524807 1985-10-08

Publications (1)

Publication Number Publication Date
WO1987002244A1 true WO1987002244A1 (en) 1987-04-23

Family

ID=10586368

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1986/000607 WO1987002244A1 (en) 1985-10-08 1986-10-08 Tissue growth regulation

Country Status (10)

Country Link
EP (1) EP0239607A1 (cs)
JP (1) JPS63501077A (cs)
AU (1) AU606038B2 (cs)
CA (1) CA1289885C (cs)
CS (1) CS265224B2 (cs)
DD (1) DD272034A5 (cs)
GB (1) GB8524807D0 (cs)
IN (1) IN168295B (cs)
WO (1) WO1987002244A1 (cs)
ZA (1) ZA867664B (cs)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0372730A3 (en) * 1988-11-18 1990-06-20 The University Of British Columbia N-acetyl glucosamine as a cytoprotective agent
US5192750A (en) * 1992-01-28 1993-03-09 The University Of British Columbia Method and composition for treatment of food allergy
US5217962A (en) * 1992-01-28 1993-06-08 Burton Albert F Method and composition for treating psoriasis
US5229374A (en) * 1992-01-28 1993-07-20 Burton Albert F Method for treatment of lower gastrointestinal tract disorders
US5273900A (en) * 1987-04-28 1993-12-28 The Regents Of The University Of California Method and apparatus for preparing composite skin replacement
WO1999053929A1 (en) * 1998-04-17 1999-10-28 Glucogenics Pharmaceuticals Inc. Composition for and treatment of inflammatory bowel disease by colon administration of n-acetylglucosamine
WO2004014398A1 (en) 2002-08-13 2004-02-19 Third Military Medical University, Chinese People's Liberation Army, P.R. Of China The use of n-acetyl-d-glucosamine for preparing medicines for urogenital tract infection’s treatment and prevention
US6992073B2 (en) 2001-02-28 2006-01-31 Third Military Medical University, Chinese People's Liberation Army Use of N-acetyl-D-glucosamine in the manufacture of a medicament for treating cervical erosion
EP1666046A4 (en) * 2003-09-17 2007-10-03 Univ Pla 3Rd Military Medical USE OF N-ACETYL-D-AMINOGLYCOSAMINE IN THE MANUFACTURE OF MEDICAMENTS FOR THE TREATMENT OF CANCER AND METASTASES
USRE41278E1 (en) 1999-01-08 2010-04-27 Yu Ruey J N-acetyl aldosamines and related N-acetyl compounds, and their topical use

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005112948A1 (ja) * 2004-05-21 2005-12-01 Tottori University 創傷の治療又は処置のための薬剤
ITBS20070178A1 (it) * 2007-11-15 2009-05-16 Paoli Ambrosi Gianfranco De Composizione per uso farmaceutico e/o cosmetico e/o in forma di dispositivo medico per favorire processi di cicatrizzazione, per il trattamento di cicatrici ipertrofiche e per migliorare le proprieta' biomeccaniche della cute

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3232836A (en) * 1959-08-24 1966-02-01 Pfizer & Co C Facilitating healing of body surface wounds by intravenous administration of n-acetyl glucosamine, glucosamine, or pharmaceutically acceptable acid salts of glucosamine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3232836A (en) * 1959-08-24 1966-02-01 Pfizer & Co C Facilitating healing of body surface wounds by intravenous administration of n-acetyl glucosamine, glucosamine, or pharmaceutically acceptable acid salts of glucosamine

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5273900A (en) * 1987-04-28 1993-12-28 The Regents Of The University Of California Method and apparatus for preparing composite skin replacement
EP0372730A3 (en) * 1988-11-18 1990-06-20 The University Of British Columbia N-acetyl glucosamine as a cytoprotective agent
US5192750A (en) * 1992-01-28 1993-03-09 The University Of British Columbia Method and composition for treatment of food allergy
US5217962A (en) * 1992-01-28 1993-06-08 Burton Albert F Method and composition for treating psoriasis
US5229374A (en) * 1992-01-28 1993-07-20 Burton Albert F Method for treatment of lower gastrointestinal tract disorders
WO1999053929A1 (en) * 1998-04-17 1999-10-28 Glucogenics Pharmaceuticals Inc. Composition for and treatment of inflammatory bowel disease by colon administration of n-acetylglucosamine
USRE41278E1 (en) 1999-01-08 2010-04-27 Yu Ruey J N-acetyl aldosamines and related N-acetyl compounds, and their topical use
USRE41339E1 (en) 1999-01-08 2010-05-18 Tristrata, Inc. N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
EP2311452A1 (en) * 1999-01-08 2011-04-20 Ruey J. Yu Topical composition comprising n-acetyl glucosamine
USRE42902E1 (en) 1999-01-08 2011-11-08 Tristrata, Inc. N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
USRE44017E1 (en) 1999-01-08 2013-02-19 Ruey J. Yu N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
USRE44302E1 (en) 1999-01-08 2013-06-18 Ruey J. Yu N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US6992073B2 (en) 2001-02-28 2006-01-31 Third Military Medical University, Chinese People's Liberation Army Use of N-acetyl-D-glucosamine in the manufacture of a medicament for treating cervical erosion
WO2004014398A1 (en) 2002-08-13 2004-02-19 Third Military Medical University, Chinese People's Liberation Army, P.R. Of China The use of n-acetyl-d-glucosamine for preparing medicines for urogenital tract infection’s treatment and prevention
EP1666046A4 (en) * 2003-09-17 2007-10-03 Univ Pla 3Rd Military Medical USE OF N-ACETYL-D-AMINOGLYCOSAMINE IN THE MANUFACTURE OF MEDICAMENTS FOR THE TREATMENT OF CANCER AND METASTASES

Also Published As

Publication number Publication date
DD272034A5 (de) 1989-09-27
GB8524807D0 (en) 1985-11-13
CS265224B2 (en) 1989-10-13
EP0239607A1 (en) 1987-10-07
AU606038B2 (en) 1991-01-31
AU6409486A (en) 1987-05-05
CA1289885C (en) 1991-10-01
ZA867664B (en) 1987-05-27
CS729286A2 (en) 1989-01-12
IN168295B (cs) 1991-03-09
JPS63501077A (ja) 1988-04-21

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