EP0239607A1 - Tissue growth regulation - Google Patents

Tissue growth regulation

Info

Publication number
EP0239607A1
EP0239607A1 EP86905906A EP86905906A EP0239607A1 EP 0239607 A1 EP0239607 A1 EP 0239607A1 EP 86905906 A EP86905906 A EP 86905906A EP 86905906 A EP86905906 A EP 86905906A EP 0239607 A1 EP0239607 A1 EP 0239607A1
Authority
EP
European Patent Office
Prior art keywords
solution
biotin
preparation
temperature
tissue growth
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.)
Withdrawn
Application number
EP86905906A
Other languages
German (de)
English (en)
French (fr)
Inventor
Neil Geddes Clarkson Hendry
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP0239607A1 publication Critical patent/EP0239607A1/en
Withdrawn legal-status Critical Current

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.

Landscapes

  • 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)
EP86905906A 1985-10-08 1986-10-08 Tissue growth regulation Withdrawn EP0239607A1 (en)

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
EP0239607A1 true EP0239607A1 (en) 1987-10-07

Family

ID=10586368

Family Applications (1)

Application Number Title Priority Date Filing Date
EP86905906A Withdrawn EP0239607A1 (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)

Families Citing this family (12)

* 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
CA1318592C (en) * 1988-11-18 1993-06-01 University Of British Columbia N-acetyl glucosamine as a cytoprotective agent
US5229374A (en) * 1992-01-28 1993-07-20 Burton Albert F Method for treatment of lower gastrointestinal tract disorders
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
US6046179A (en) * 1998-04-17 2000-04-04 Murch; Simon Composition for and treatment of inflammatory bowel disease by colon administration of N-acetylglucosamine
US6159485A (en) * 1999-01-08 2000-12-12 Yugenic Limited Partnership N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
CN1173706C (zh) 2001-02-28 2004-11-03 中国人民解放军第三军医大学 N-乙酰-d-氨基葡萄糖在制备治疗宫颈糜烂药物中的应用
CN1199645C (zh) 2002-08-13 2005-05-04 中国人民解放军第三军医大学 N－乙酰－d－氨基葡萄糖在制备治疗泌尿生殖道感染药物中的应用
AU2003271016A1 (en) * 2003-09-17 2005-04-06 Bio-Wave Institute Of Suzhou Hi-Tech New District Corporation, Ltd. Use of n-acetyl-d-aminoglycosamine in preparation of drugs for the treatment of cacer and metastasis
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

Family Cites Families (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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8702244A1 *

Also Published As

Publication number Publication date
DD272034A5 (de) 1989-09-27
GB8524807D0 (en) 1985-11-13
CS265224B2 (en) 1989-10-13
WO1987002244A1 (en) 1987-04-23
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

Similar Documents

Publication Publication Date Title
US4707471A (en) Water-soluble aminated β-1,3-bound D-glucan and composition containing same
US4708965A (en) Method of treating herpes virus infections with N,N'-diacetylcystine and derivatives
EP0239607A1 (en) Tissue growth regulation
KR100332250B1 (ko) 2',5'-올리고아데닐레이트2',3'-시클로포스페이트
Johnson Biological acetylation of isoniazid
JPS6152125B2 (cs)
WO1992002231A1 (fr) Agent anti-vih
US4330527A (en) Wound treatment agent
JPH0427964B2 (cs)
CZ293353B6 (cs) Farmaceutický prostředek pro prevenci nebo léčení poruchy růstu vlasů
Pouillart et al. Trial of BCG immunotherapy in the treatment of resectable squamous cell carcinoma of the bronchus (stages I and II)
US6992073B2 (en) Use of N-acetyl-D-glucosamine in the manufacture of a medicament for treating cervical erosion
DE69021024T2 (de) Pharmakologisch aktive Substanz BPC, Verfahren zu ihrer Herstellung und ihre Verwendung.
Seegmiller et al. Excessive uric acid production in the human induced by 2-ethylamino-1, 3, 4-thiadiazole
JPH0245495A (ja) ビスマス（リン酸／硫酸）サッカリド
JP3040711B2 (ja) 抗腫瘍剤及びその製造法
BG61191B1 (bg) Методът за получаване на телесно защитно вещество ВРС от човешки или животински стомашен сок, се характеризира със следните етапи на производство: събраният и хомогенизиран животински или човешки стомашен сок се разделя на твърди части и течна супернатанта чрез центрофугиране; течната супернатанта се диализира и лиофилизира; сухият остатък се пречиства през хроматографска колона, напълнена със слабо алкална, модифицирана йонообменна смола или гел; концентратът отново се диализира и лиофилизира; сухият остатък се пречиства чрез гел- хроматография; веществото ВРС се получава накрая от концентрата при използване на диализа и лиофилизация.
RU2235550C2 (ru) Лекарственное средство бионормализующего действия и способ его получения
US5849783A (en) Autobiotics and their use in eliminating nonself cells
RU2110272C1 (ru) Средство для лечения термических поражений кожи, трофических язв, пролежней и длительно незаживающих ран
RU2314814C2 (ru) Ксеногенные олиго- или/и полирибонуклеотиды в качестве средств для лечения злокачественных опухолей
JPH04187640A (ja) 経口・経皮免疫機能促進剤、動物用経口・経皮免疫機能促進剤
RU2169553C1 (ru) Гель для лечения ран
DE3236298C2 (cs)
JP2889491B2 (ja) 血圧降下剤

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

17P Request for examination filed

Effective date: 19871015

17Q First examination report despatched

Effective date: 19890531

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Withdrawal date: 19920222