AU8321691A - Therapeutic use of ranitidine in the treatment of wounds to the skin and underlying tissues - Google Patents
Therapeutic use of ranitidine in the treatment of wounds to the skin and underlying tissuesInfo
- Publication number
- AU8321691A AU8321691A AU83216/91A AU8321691A AU8321691A AU 8321691 A AU8321691 A AU 8321691A AU 83216/91 A AU83216/91 A AU 83216/91A AU 8321691 A AU8321691 A AU 8321691A AU 8321691 A AU8321691 A AU 8321691A
- Authority
- AU
- Australia
- Prior art keywords
- wounds
- ranitidine
- skin
- treatment
- underlying tissues
- 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.)
- Abandoned
Links
- 206010052428 Wound Diseases 0.000 title claims description 26
- 208000027418 Wounds and injury Diseases 0.000 title claims description 26
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 title claims description 20
- 229960000620 ranitidine Drugs 0.000 title claims description 20
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 238000000034 method Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 230000035876 healing Effects 0.000 claims description 5
- 230000000699 topical effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 2
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims 1
- 229940045145 uridine Drugs 0.000 claims 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 7
- 229960001340 histamine Drugs 0.000 description 7
- 230000009471 action Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 3
- 206010063560 Excessive granulation tissue Diseases 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 231100000321 erythema Toxicity 0.000 description 3
- 210000001126 granulation tissue Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 206010020565 Hyperaemia Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000001175 peptic effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 101100270435 Mus musculus Arhgef12 gene Proteins 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 208000022061 active hyperemia Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 108010080511 serum sodium transport inhibitor Proteins 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
Description
- 1 -
THERAPEUTIC USE OF RANITIDINE IN THE TREATMENT OF WOUNDS TO THE SKIN AND UNDERLYING TISSUES
_ Technical field
The present invention refers to a new indication for the 5 therapeutic use of ranitidine.
The new therapeutic use of the molecule refers to the treatment of wounds to the skin and to underlying tissues showing a slow tendency to heal with the intervention of repair procedures which evolve by second intention. 10 This is what occurs, for example, in the case of large- scale loss of substance, un-stitched wounds, infected wounds, lacerations, dehiscent surgical wounds, bed sores, and the like.
Background art 15 Ranitidine is known to be active in gastritis and in ulcers as a H2-receptor blocking agent.
Its chemical denomination is N-[2-(5- dimethylaminomethylfurfurylthio)-ethyl]-N/-methyl-2-nitro- 1,1-ethylenediamine. 20 It is known that ranitidine is a powerful antihistaminic agent, or H2-antagonist, capable of greatly inhibiting gastric secretions, and therefore it is currently used in the treatment of peptic gastroduodenal ulcers and in all those pathologies in which the hydrochloride peptic secretions of 25 the stomach play a fundamentally important part.
It is also known, on the other hand, that histamine has a pre-eminent activity in inflammatory processes, which justifies its use, by some researchers, in certain particular flogistic conditions, such as sunburn and acne. 30 Recently, a direct action of histamine itself in tissue repair processes has also been underlined.
It has in fact been observed (see Dabrowski and Maskinski, Agents and Actions 1981; 11:122-24) that histamine has a direct influence on the synthesis, the polimerization 35 and the deposit of collagen in the granulation tissue of wounds. In particular, it has been observed that minimum concentrations of histamine show an action which favours the production of collagen, whereas high doses of histamine cause
the opposite effect.
This double action of histamine has been found to b mediated by H2-type histamine receptors, as said actio appears to be completely inhibited by cimetidine, wherea anti-Hl (mepyramine) drugs do not appear to have th slightest influence.
Disclosure of the invention
It has therefore been surprisingly discovered, accordin to the present invention, that ranitidine, although it is drug known for its antihistamine activity, is shown to have favourable effect in the healing of external wounds, wher the favourable action of histamine has been experimented.
Object of the present invention is therefore the ne therapeutic use of ranitidine in the treament of wounds t the skin and to the underlying tissues showing a slo tendency to heal, in particular due to the effect of repai processes evolving by second intention.
Ranitidine is particularly useful in those continua wounds which heal by second intention, in which the greates inflammation effects can be observed.
The mechanism of action which can be supposed for sai activity, appears actually to be connected to the larg quantity of endogenous amines produced by the flogisti process, which could determine, as a result of an inhibitin activity on the production of collagen, a delay in th healing of the wound itself. Pharmacological tests.
The following clinical tests were carried out. Fourty subjects having a continual lesion of the skin an of the underlying tissues, evolving towards healing by secon intention, were sub-divided into two groups, comparable as to site, size and state of the wound.
All those patients were excluded in whom factors of a local or general nature could have interfered with the healing process, such as serious hypodisprotidemia, mellitus diabetes, serious anemia, local circulatory alterations, etc.
The size of the wound was evaluated, by measuring bot the extent and depth of the wound and the volume of the
residual hollow.
The state of the wounds was divided into five classes: 1 - absence of erythema on the surrounding skin;
2 - presence of erythema on the surrounding skin, disappearing on digital pressure (active hyperemia) ;
3 - presence of erythema on the surronding skin, which does not disappear on digital pressure (passive hyperemia) ;
4 - presence of tissue necrosis;
5 - presence of infection. Both groups underwent medication of the wound every other day using the same methods.
In both groups, the wound was cleaned, disinfected and if necessary isolated using Dakin's solution. Following this, for patients in the first group only, a topical application of ranitidine at a concentration of 10 mg/ml was made, using the amount of 1 cm3 of solution for every 3 ml of loss of substance.
The wounds treated with ranitidine showed a more rapid tendency to heal. The number of days required to completely fill in the loss of substance was found to be reduced by approximately one quarter in the group treated with ranitidine, compared with the control group.
Even the daily percentage of reduction of the wound hollow appeared greater in the subjects treated with ranitidine, sometimes by as much as 40-50%, indicating a stimulating action on the deposit of granulation tissue.
It therefore appears that the topical use of ranitidine in continuous lesions with a tendency to heal by second intention has been proved to be of undoubted use.
The action favouring the neoformation of granulation tissue showed by the drug can be translated, in fact, into a more rapid obliteration of the wound hollow, greatly shortening the time necessary for cicatrization of ne wound itself.
Further tests carried out in similar conditions have shown the benefits of ranitidine when used according to the present invention, in various topical compositions containing
a concentration of ranitidine comprised between 3 and 30 g o active substance per 1000 ml of composition.
The pharmaceutical composition containing ranitidine fo the use indicated can be in the form of a solution, a emulsion, containing ranitidine alone, or in combination with other auxiliary active agents.
Claims (4)
- CLAIMS 1. Use of ranitidine for the manufacture of a medicament for the topical treatment of wounds to the skin and/or to the underlying tissues.
- 2. Use of ranitidine according to claim 1, in which said wounds are continual wounds which tend to heal by second intention.
- 3. A pharmaceutical agent for the topical treatment of wounds to the skin and, or to the underlying tissues comprising ranitidine.
- 4. A method for the treatment of wounds to the skin and, or to the underlyhing tissues comprising applying topically to said wound an amount of uridine effective to aid the healing thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT48186/90 | 1990-07-31 | ||
| IT48186A IT1241521B (en) | 1990-07-31 | 1990-07-31 | THEPERAUTIC USE OF RANITIDINE IN THE TREATMENT OF INTERESTING WOUNDS SKIN AND THE UNDERLYING FABRICS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU8321691A true AU8321691A (en) | 1992-03-02 |
Family
ID=11265095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU83216/91A Abandoned AU8321691A (en) | 1990-07-31 | 1991-07-29 | Therapeutic use of ranitidine in the treatment of wounds to the skin and underlying tissues |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0495060A1 (en) |
| JP (1) | JPH04506364A (en) |
| KR (1) | KR920702218A (en) |
| AU (1) | AU8321691A (en) |
| IT (1) | IT1241521B (en) |
| WO (1) | WO1992002218A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2070531B1 (en) * | 2007-12-10 | 2019-08-07 | ITALFAR S.r.l. | Pharmaceutical preparation containing histamine H2-receptor antagonists having wound healing activity at low doses |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU201683B (en) * | 1987-08-04 | 1990-12-28 | Biogal Gyogyszergyar | Process for producing pharmaceutical compositions for promoting healing of wounds |
-
1990
- 1990-07-31 IT IT48186A patent/IT1241521B/en active IP Right Grant
-
1991
- 1991-07-29 JP JP3513240A patent/JPH04506364A/en active Pending
- 1991-07-29 KR KR1019920700722A patent/KR920702218A/en not_active Ceased
- 1991-07-29 WO PCT/IT1991/000068 patent/WO1992002218A1/en not_active Ceased
- 1991-07-29 AU AU83216/91A patent/AU8321691A/en not_active Abandoned
- 1991-07-29 EP EP91914405A patent/EP0495060A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| IT9048186A1 (en) | 1992-01-31 |
| EP0495060A1 (en) | 1992-07-22 |
| JPH04506364A (en) | 1992-11-05 |
| IT9048186A0 (en) | 1990-07-31 |
| WO1992002218A1 (en) | 1992-02-20 |
| KR920702218A (en) | 1992-09-03 |
| IT1241521B (en) | 1994-01-17 |
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