EP0239607A1 - Regulierung des wachstums von geweben - Google Patents
Regulierung des wachstums von gewebenInfo
- 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- Withdrawn
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.
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 (de) | 1987-10-07 |
Family
ID=10586368
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP86905906A Withdrawn EP0239607A1 (de) | 1985-10-08 | 1986-10-08 | Regulierung des wachstums von geweben |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP0239607A1 (de) |
JP (1) | JPS63501077A (de) |
AU (1) | AU606038B2 (de) |
CA (1) | CA1289885C (de) |
CS (1) | CS265224B2 (de) |
DD (1) | DD272034A5 (de) |
GB (1) | GB8524807D0 (de) |
IN (1) | IN168295B (de) |
WO (1) | WO1987002244A1 (de) |
ZA (1) | ZA867664B (de) |
Families Citing this family (12)
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***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 |
EP1666046A4 (de) * | 2003-09-17 | 2007-10-03 | Univ Pla 3Rd Military Medical | Verwendung von n-acetyl-d-aminoglycosamin bei der herstellung von arzneimitteln zur behandlung von krebs und metastasen |
JP4496375B2 (ja) * | 2004-05-21 | 2010-07-07 | 国立大学法人鳥取大学 | 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)
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 |
-
1985
- 1985-10-08 GB GB858524807A patent/GB8524807D0/en active Pending
-
1986
- 1986-10-07 CA CA000520028A patent/CA1289885C/en not_active Expired - Lifetime
- 1986-10-08 CS CS867292A patent/CS265224B2/cs unknown
- 1986-10-08 JP JP61505290A patent/JPS63501077A/ja active Pending
- 1986-10-08 DD DD86295099A patent/DD272034A5/de not_active IP Right Cessation
- 1986-10-08 IN IN896/DEL/86A patent/IN168295B/en unknown
- 1986-10-08 EP EP86905906A patent/EP0239607A1/de not_active Withdrawn
- 1986-10-08 WO PCT/GB1986/000607 patent/WO1987002244A1/en not_active Application Discontinuation
- 1986-10-08 ZA ZA867664A patent/ZA867664B/xx unknown
- 1986-10-08 AU AU64094/86A patent/AU606038B2/en not_active Ceased
Non-Patent Citations (1)
Title |
---|
See references of WO8702244A1 * |
Also Published As
Publication number | Publication date |
---|---|
AU6409486A (en) | 1987-05-05 |
IN168295B (de) | 1991-03-09 |
JPS63501077A (ja) | 1988-04-21 |
WO1987002244A1 (en) | 1987-04-23 |
AU606038B2 (en) | 1991-01-31 |
CS265224B2 (en) | 1989-10-13 |
CS729286A2 (en) | 1989-01-12 |
CA1289885C (en) | 1991-10-01 |
DD272034A5 (de) | 1989-09-27 |
ZA867664B (en) | 1987-05-27 |
GB8524807D0 (en) | 1985-11-13 |
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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 |