WO2000074691A1 - Treatment of cutaneous leishmaniasis and other dermatological diseases mainly wounds (diabetic ulcers) by idogenos sanhory - Google Patents
Treatment of cutaneous leishmaniasis and other dermatological diseases mainly wounds (diabetic ulcers) by idogenos sanhory Download PDFInfo
- Publication number
- WO2000074691A1 WO2000074691A1 PCT/IB1999/001422 IB9901422W WO0074691A1 WO 2000074691 A1 WO2000074691 A1 WO 2000074691A1 IB 9901422 W IB9901422 W IB 9901422W WO 0074691 A1 WO0074691 A1 WO 0074691A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- treatment
- idoeugenol
- wounds
- leishmanol
- cutaneous leishmaniasis
- Prior art date
Links
- 206010052428 Wound Diseases 0.000 title claims abstract description 40
- 208000027418 Wounds and injury Diseases 0.000 title claims abstract description 40
- 206010011668 Cutaneous leishmaniasis Diseases 0.000 title claims abstract description 34
- 206010056340 Diabetic ulcer Diseases 0.000 title claims abstract description 16
- 238000011282 treatment Methods 0.000 title claims description 49
- 201000010099 disease Diseases 0.000 title abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 11
- 241001465754 Metazoa Species 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 abstract description 34
- 230000003902 lesion Effects 0.000 abstract description 19
- 208000025865 Ulcer Diseases 0.000 abstract description 17
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 16
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 14
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 abstract description 14
- 231100000397 ulcer Toxicity 0.000 abstract description 14
- 244000045947 parasite Species 0.000 abstract description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 10
- 230000035876 healing Effects 0.000 abstract description 9
- 229960002217 eugenol Drugs 0.000 abstract description 8
- 239000001301 oxygen Substances 0.000 abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 7
- 239000008213 purified water Substances 0.000 abstract description 7
- 241000894006 Bacteria Species 0.000 abstract description 3
- ODUCDPQEXGNKDN-UHFFFAOYSA-N Nitrogen oxide(NO) Natural products O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 abstract description 3
- 208000015181 infectious disease Diseases 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 abstract 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 abstract 3
- 210000001519 tissue Anatomy 0.000 description 14
- 229940079593 drug Drugs 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
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- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 4
- 239000005770 Eugenol Substances 0.000 description 4
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
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- 239000001257 hydrogen Substances 0.000 description 3
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- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
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- 238000002360 preparation method Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
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- 231100000331 toxic Toxicity 0.000 description 3
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- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010012436 Dermatitis artefacta Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
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- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- VKVCLXDFOQQABP-UHFFFAOYSA-N 2-[2-(diaminomethylideneamino)ethylsulfanyl]butanedioic acid Chemical compound NC(N)=NCCSC(C(O)=O)CC(O)=O VKVCLXDFOQQABP-UHFFFAOYSA-N 0.000 description 1
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- 206010017533 Fungal infection Diseases 0.000 description 1
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- 241000976924 Inca Species 0.000 description 1
- 208000006877 Insect Bites and Stings Diseases 0.000 description 1
- DKNPRRRKHAEUMW-UHFFFAOYSA-N Iodine aqueous Chemical compound [K+].I[I-]I DKNPRRRKHAEUMW-UHFFFAOYSA-N 0.000 description 1
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- QTENRWWVYAAPBI-YZTFXSNBSA-N Streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@H]1[C@H](N=C(N)N)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@H]1[C@H](N=C(N)N)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]1O QTENRWWVYAAPBI-YZTFXSNBSA-N 0.000 description 1
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- 229960004125 ketoconazole Drugs 0.000 description 1
- 230000000724 leishmaniacidal effect Effects 0.000 description 1
- QTWZICCBKBYHDM-UHFFFAOYSA-N leucomethylene blue Chemical compound C1=C(N(C)C)C=C2SC3=CC(N(C)C)=CC=C3NC2=C1 QTWZICCBKBYHDM-UHFFFAOYSA-N 0.000 description 1
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- 150000002926 oxygen Chemical class 0.000 description 1
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- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
- 229960004448 pentamidine Drugs 0.000 description 1
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- GPKJTRJOBQGKQK-UHFFFAOYSA-N quinacrine Chemical compound C1=C(OC)C=C2C(NC(C)CCCN(CC)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 GPKJTRJOBQGKQK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
-
- 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
-
- 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
- A61K33/18—Iodine; Compounds thereof
-
- 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
- A61K33/40—Peroxides
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the disease manifest itself ⁇ in different clinical forms ACL, recurrent RCL, and diffuse Cutaneous leishmanisis DCL. some of these manifestation may heal within a period of
- the antimonials, amphotercin and pentamidinde are complicated to use and 20 are not suitable for extensive use in chronic cases of cutaneous leishmaniasis.
- 9ystematic treatment with antimonial requires hospitalization and produced adverse reactions in some patients; application of these intralesionally is painful, requires certain skill and may not always produce complete healing.
- Amphotercin and pentamidine are highly toxic and are recommended for use only in cases that fail to respond to pentavelent antimonials or are suffering from DCL.
- Rifampicin is one of the few firstline 30 drugs for treatment of tuberculosis. Therefore, to use is limited for the treatment of cutaneous leishmaniasis, ketoconazol is potentially high toxic and expensive drug.
- leishmania overcome the micro biocidal conditions of the monocyte (phagolysosomes), which include proton pumps to balance pH and enzymes to detoxify oxygen metabolites and other leishmanicidal products are well known to us where the main mechanism by which leishmania are killed is increased production of oxygen stimulated in macrophages by the new drug Ideougenol Qanhory compound (leishmanol) during interaction with citric acid cycle.
- Idoeugenol Qanhory contains 17.5% (Eugenic acid), occurrence eugenol is the main constituent of several important volatile oils belonging to the family Myrtaceaseae and lauraceae.
- Clinical hematology index (sick animals with septic wound) was study about 2 years.
- the number of lesions in single patient ranging from 1-22 (mean, 11.5)
- the duration of lesions ranged from 1-3 months (mean 2 month). Patients were blindly divided into a study , group with Idoeugenol is and control group (given placebo).
- the drug was typically applied, to the ulcerative lesions at the clinic, twice during the whole period of study, once on the first day and the other on the third day of the visit. Similarly placebo was applied to the lesions of the patients.
- the time of resolution ranged from 2-8 weeks (means 5 weeks).
- This method is suitable for high-risk patients with cardiopulmonary of liver diseases or having limited renal reserve and septic wounds [mainly diabetic ulcers). ⁇ >n Additionally, topical application may be of considerable importance in combating epidemics or in mass treatment of cutaneous leismaniasis.
- the time of resolution ranged from (1-9 weeks means 4-5 weeks) It has been noticed that the healing time and cure depend on the size of the wound, (ulcer) age and health of the patient.
- the initial therapy showed the high efficiency and quality of idoeugenols (leishmanol) compound in the treatment of diabetic wounds (ulcers) without any side effects noted in the treated patients. 5
- Table "A" life table stimates of the incidence (% ) of complete healing over time for study of treatment of diabetic ulcers by (I.E.S) leishmanol, Idoeugenol compound.
- Table "B” life table stimates of the incidence (% ) of complete healing over time for study of treatment of septic ulcers by (I .E.S) leishmanol,
- Table "C” life table stimates of the incidence (% ) of complete healing over time for study of treatment of superficial wounds by (I.E.S) leishmanol, Idoeugenol compound.
- Idoeugenol sanhory (I.E. ⁇ ) was used in the treatment of around 15OOO [fifteen thousand] volunteer patients with different-diseases mainly cutaneous leishmaniasis, and septic/aseptic wounds mainly diabetic ulcers. During the above period, no side - effects were noted after the administration of a new drug I.E. ⁇ (Idoeugenol sanhory). In the control group no significant healing changes were obtained in patients to whom placebo was prescribed.
- Citric acid [(OH) C H (COOH J], (0.187 ⁇ 0.002) > (0.243 ⁇ 0.0001)
- I.E.S Leishmanol compound which penetrate and diffuses into the affected tissues in reaction 0 to (AMP) cycle which released active oxygen which causes rapture in the Membrane cell of macrophage by oxidation of phospolipds membrane which increased the production of oxygen stimulated in macropage by which amostigate parasite causes cutaneous leishmaniasis to be killed.
- I.E. ⁇ compound Leishmanol
- Idoeugenol penetrates and defuses deep into the affected tissues which oxidizes hydrogen ⁇ ulfide to form hydrogen 15 Iodide and active cysteine and liberate sulfur, which is very clear in the yellowish color[medical photo] after the application the drug I.E. ⁇ into affected tissues figure NO. [11/12].
- Idoeugenol Sanhory compound (Leishmanol) has practically good clinical effects on the treatment of cutaneous leishmaniasis (ulcers), (lesion) and wounds. Mainly diabetic ulcers.
- the present invention controls and treats, cutaneous leishmaniasis (CL) which is caused by three species of leishmania L tropica.
- L. major, L. a ethiopica also treats, urban cutaneous leishmanias (ACL), venezulensis cutaneous leishmaniasis, defuses cutaneous lieshmaniasis [DCL].
- the present invention controls and treats wounds and ulcers , mainly diabetic ulcers, ostemyolitis wounds, bullet wounds, incas wounds, penetrate wound, punctured wound, septic wound, aseptic wound, and also ideugenol is highly effective in superficial wounds.
- the present invention also treats and controls other dermatolegical disease, dermatitis artefacta lips, dermatitis artefacta side of face. Insect bites, fungal infection, dermatitis eczema, dermatitis lesions ulcers, and highly effective in the treatment of alopecia areata adult, and acne mainly acne after shaving (Saniorra 1% - 5% ideugenol. 8.). & • hilly effective in treatment of hair dandruff
- Figure No 1 a table showing conservation initial substrate redox process
- FIG. No 2. is graph showing the parasiticl examination study group before & after treatment by idoeugenol. s. [Leishmanol].
- Figure No 3. a table showing the parasitical examination study group.
- Figure No 4. a table showing the parasitical examination study group before & after treatment by placebo.
- Figure 4A. showing [CL] ulcers before & after treatment by idoeugenol
- Figure No 10.1 1 are graphs shwing local temperature in the affected tissues, before and after application by Idoeugenol compound [Lieshmanol].
- Figure No 12 is a graph showing the parasitical examination study group before
- Figure No 12b showing rose shape of promostigate parasite before treatment.
- Figure No 12c Histopathological examination showing amostigate parasite before treatment.
- Figure No 13 is a graph showing the duration of treatment of cutaneous
- AMP monophosfate
- Test interval 0 Samples stored at 40c will be tested monthly for ⁇ months for the following test:
Abstract
A method of substantially treating of cutaneous leishmaniasis and other dermatological diseases by idoeugenol Sanhory compound (leishmanol). Dosage formulation being from about 15 to 17.5 gm Eugenic acid, 2.5 gm iodine, 2.5 gm potassium iodide, 50 ml ethanol and purified water (USP), required to treat and control cutaneous leishmaniasis (CL) approximately 100 % of patients. Formulation provides active oxygen (O2) and also nitrogen oxide (No) which killed amostigate parasite from a mean of about 5 minutes to 10 minutes and complete healing of ulcers and lesions of cutaneous leishmaniasis from a mean of about one week to six weeks. A method of substantially treating of diabetic ulcers by Idoeugenol Sanhory (leishmanol) dosage formulation having from about 15 to 17.5 gm eugenic acid, 2.5 gm iodine, 2.5 gm potassium iodide, 50 ml ethanol and purified water (USP) required to treat and control diabetic ulcers approximately 94 % of patients, from a mean of about 5 minutes to 10 minutes. Complete healing of ulcers from a mean of about one week to 8 weeks. A method of substantially treating of superficial wounds (septic, aseptic) dosage formulation being from about 15 to 17.5 gm eugenic acid, 2.5 gm iodine, 2.5 gm potassium iodide, 50 ml ethanol and purified water (USP); required to treat and control superficial wounds approximately 99 % of patient formulation provide active oxygen (O2) and nitrogen oxide (NO) which killed bacteria causes infection from a mean of 5 minutes to 10 minutes and complete healing of wounds from a mean of 24 hours to one week.
Description
TREATMENT OF CUTANEOUS LEISHMANIASIS AND OTHER DERMATOLOGICAL DISEASES MAINLY WOUNDS (DIABETIC ULCERS) BY IDOGENOS SANHORY
BY L.E.S
(C I I O .1 . KI. CM . CH OH.)
BACK GROUND OF THE INVENTION
* Cutaneous leishmaniasis in an endemic disease that continuous to present a a serious therapeutic problem throughout the world.
Depending on the type of the infecting agent the disease manifest itself \ in different clinical forms ACL, recurrent RCL, and diffuse Cutaneous leishmanisis DCL. some of these manifestation may heal within a period of
10 several month while the others may persist for years and sometimes for life. The persistent forms of cutaneous leishmanisis are difficult to treat and are to be associated with impaired immune response.
Many therapeutic modalities for treatments of cutaneous leishmaniasis have been tried, these include physical therapy and chemotherapy however, none
* * of these has proved to be satisfactory.
Among the various physical therapy, which are not is accessible to all patients
Qurgical therapies might cause dissemination of the disease.
The antimonials, amphotercin and pentamidinde are complicated to use and 20 are not suitable for extensive use in chronic cases of cutaneous leishmaniasis.
9ystematic treatment with antimonial requires hospitalization and produced adverse reactions in some patients; application of these intralesionally is painful, requires certain skill and may not always produce complete healing.
25 Amphotercin and pentamidine are highly toxic and are recommended for use only in cases that fail to respond to pentavelent antimonials or are suffering from DCL.
Among the several oral drugs attempted rifampicin and etoconazole are found to be the most effective ones. Rifampicin is one of the few firstline 30 drugs for treatment of tuberculosis. Therefore, to use is limited for the treatment of cutaneous leishmaniasis, ketoconazol is potentially high toxic and expensive drug.
Immune therapy approaches have also been attempted but this seems to be expensive and it's not widely accessible type of therapy. * ^ Treatment with systematic antimonials is too toxic for use. Local infections of antimonial 10% solution of barberin\ sulfate, a 5% solution of mepacrine
or emetrine have been used. Topical ointments are used but have not been adequately evaluated.
Physical treatment such as curettage, Gretna rays, (long wavelength X-rays) local heat and freezing are also used.
Hundred research centers around the world are still trying to reach satisfactory treatment for cutaneous leishamanisis.
Although cutaneous leishmaniasis is the most common manifestations of infection, there is no well-established treatment (WHO report 1990)'.
The mechanisms whereby leishmania overcome the micro biocidal conditions of the monocyte (phagolysosomes), which include proton pumps to balance pH and enzymes to detoxify oxygen metabolites and other leishmanicidal products are well known to us where the main mechanism by which leishmania are killed is increased production of oxygen stimulated in macrophages by the new drug Ideougenol Qanhory compound (leishmanol) during interaction with citric acid cycle.
The efficacy of idoeugenol's (leishmanol) has been proved in animals in 1986 the Ukraine Agriculture Academy in the course of postgraduate comparative study between physical therapy ulra violet [UV] parley with my individual trial of chemotherapy compound (Idoeugenol 9anhory) in reaction with cribs cycle serum blood in small animals.
Idoeugenol Qanhory contains 17.5% (Eugenic acid), occurrence eugenol is the main constituent of several important volatile oils belonging to the family Myrtaceaseae and lauraceae.
Trial of the efficacy of idoeugenol L.9. (Leishmanol) has been carried out in (1985-1989) in the department of clinical diagnosis and the department of biochemistry of the Ukraine Agriculture Academy and Institute of Oncology. Qamples were investigated 1250 [one thousands tow hundred fifty] blood serum samples.
Part of them 480 samples were serological investigated by biochemical method with the some purpose of determining substrate, enzymes acids - alkalis. On the balance (pH). Qmear test have been done (250), and histopathological analysis (67). Before starting a fundamental experiment I tested activity of Idoeugenol 8. (leishmanlo) on the organism of healthy small animals different dosage 1.5 ml, 3.5 ml, 10 ml. up to 20 ml. and made toxicological investigations. 8mall laboratory animals showed great tolerance for the drug 20-ml (leishmanol) caused no mortality among those animals and no side effects were observed. No change was observed on the (pH) or aminotanspherses enzymes and cribs cycle acids. In infected animals, white count and hemoglobin normalized after five days with the appearance of moncytes and
eosinophils in the peripheral blood. (pH) change in effected animals returned to normal following treatment with idoeugenol ,s. (leishmanol). The Trial in animals was carried out over 14 weeks, mainly through clinical investigation and general analysis of serum blood.
From the above biochemical investigation of serum blood, we did not remark any significant alteration of index acids-alkalize equilibrium, Activity 5 aminopherases on the level of substrate oxidation reduction reaction in healthy animals invariable in cribs cycle acids, mainly lactic acid, pyroracemic acid, citric acid, apple acid, glutamic acid, oxaloacitic acid. From the above results of experiment on healthy and sick animals, the drug idoeugenoL .8. (leishmanol) demonstrated that it had no side effect on the
*■" organism of experimental animals.
Clinical hematology index (sick animals with septic wound) was study about 2 years.
In the investigation blood serum of animals with septic wounds we observed that after 5 days contents of hemoglobin and quantity of erythrocyte 5 normalized, and leucocytosis disappeared.
In leuco form we pbserved decrease in neutrophilia. Esinophiles and monocytes appeared in all investigated sick animals. Before treatment we found out the level of acids- alkalize equilibrium blood sick animals of septic wounds, (7.32-734) m mol/ 1 decreases activity metabolity component shift
20 buffer basic (1.5-3.2)m mol/ 1 concentration bicarbonate (22.27-25.2) m mol/L
The normalized acids - alkalize equilibrium blood sick animals, which partially decreased the pressure carbon dioxide gas (49.52 +_ 0.1.2; 36.0 +_ 0.54) m mol/1]. and the shift of buffer basic from negative to positive (1:2.5 +_
25 0.27 - 3.4 + 0.27) m mol/1.
In the basic of the above experiment of a new compound idoeugenoL .8. (leishmanol) which it proved efficacy in the treatment of septic wounds and [CL] ulcers. It have been trialed in 450 (four houndred fifty) volunteer patients of cutaneous leishmaniasis and 170 (one houndered seventy) 0 volunteer patients with different septic &■ aseptic wounds including diabetics wounds which established the efficacy of idoeugentoL .8. compound (leishmanol) (1989-1990). experiment of the efficacy of Idoeugenol (Leishamnol) compound in the medical field on the treatment of cutaneous leishmaniasis started on July, 5 1992 and terminated In June 1993. experiment were done in Khartoum Teaching Hospital [skin &• STPs], the Tropical Research Center, Khartoum Microbiology National Health Laboratory
Department of pharmaceutical chemistry [faculty of pharmacy] University of Khartoum. Michigan laboratory of National Health.
In our trial 102 patients (Male 66, female 36), with age range 3-70 years (mean 36.5 years). Reported at the skin and [STDs] teaching hospital in the period from July 92- June 1993, with typical cutaneous leishmaniasis, diagnosis was confirmed in each patient clinically and by detection of the parasite by direct smear obtained from the edges of the lesions using leishman stain parasite were microscopically examined on smears obtained from the edges of the lesions after removing the crust, about 920 slides were tested in 6 months of the study by leishman stain, gemsa stain, buffer water 7.2. Primary isolation of culture of cutaneous leishmaniasis the parasites were initially isolated in NNN medium, this culture medium in a blood agar was finally disposed in small sterile containers and they were put in a starting position until the agent become cool. One percent of the penciling and streptomycin solution was added to reduce any cross contamination. The parasite was isolated from the cutaneous lesion after the lesion has been cleaned. Culture and histopathological studies were done in some patients. General investigation was carried out for all patients before and and after treatment. This examination was done on all lesions prior to treatment and weekly up to 5 and 8 weeks after treatment. Patients were followed up 6 months from the beginning of the treatmetn.
Most patients had multiple skin lesions: the total number of lesions was 446
- 370 of the typical ulcerative 76 of the dry nodular type.
The number of lesions in single patient ranging from 1-22 (mean, 11.5)
The duration of lesions ranged from 1-3 months (mean 2 month). Patients were blindly divided into a study , group with Idoeugenol is and control group (given placebo).
The drug was typically applied, to the ulcerative lesions at the clinic, twice during the whole period of study, once on the first day and the other on the third day of the visit. Similarly placebo was applied to the lesions of the patients.
Of the total 102 patients studied, 92 patients (male 60, female 32) had completed the study period (72 of the study group and 20 of the control group).
52 patients of the study group had ulcerative and nodular types of lesions. The lesions treated with idoeugenol .8. (leishmanol drug) showed improvement usually within (7-14) days after the applications.
In 68 patients (94.65 %) the smear was negative after one week from the application of the drug (I.E.8.) and other 4 patients (5.35% smear was negative after two weeks.
In 53 patients (73.33%) lesions healed completely without ascar or any 5 pigmentary changes (tab 6).
In 19 patients (26.67%) lesions healed with minimal scarring and hypopigmentation.
None of the control group (20 patients) showed any clinical laboratory response to the treatment by placebo (table 4). 10 Recent investigations have shown that the idoeugenol.8. (leshmanol) has promising aneous effect against cuts, leishamansis and secondary bacterial infection mainly septic wounds (diabetic ulcers) sanhoury 1992).
The time of resolution ranged from 2-8 weeks (means 5 weeks).
Almost all of the lesion treated with idougenol.8. (leishmanol) healed without 15 significant disfigurement or scarring.
A few patients showed transient hyper/hypo pigmentary changes at the site of original lesions. However, these disappeared towards the end of the study
(6 months).
Following - up the patients for 6 months after the initial therpay, showed the 20 persistent effectiveness of the treatment by idougenol.8. compound, and no side - effects were noted in the treated patients. No significant changes were observed in patients to whom the placebo was prescribed. (Control
Group), tab 4).
The results of this study indicate that the methods applied for the treatment 25 of the cutaneous leishmaniasis, by idougenol.8. (leishmanol) are technically simple, safe, easily administered and yet highly effective.
This method is suitable for high-risk patients with cardiopulmonary of liver diseases or having limited renal reserve and septic wounds [mainly diabetic ulcers). ■>n Additionally, topical application may be of considerable importance in combating epidemics or in mass treatment of cutaneous leismaniasis.
In a medical filed trial experimental of the efficacy of idougenol.8. compound
(leishmanol) on treatment of wounds and mainly diabetic wounds carried out in 1997 and determined in 1998 at the Diabetic and Endocrine Center in 5 Khartoum North and the National Health Laboratory Khartoum. A total of 86 patients (female 50, male 36) had completed the trial period, 70 of the study group and 16 of the control group.
Diagnosis was confirmed in each patient clinically and by swab examination mainly streptococci and staphylococci. The result of this trial showed that idoeugenol.8. compound (leishmanol) is highly effective and safe in the
treatment of diabetic wounds (ulcers), without failure in any patients so far treated.
The time of resolution ranged from (1-9 weeks means 4-5 weeks) It has been noticed that the healing time and cure depend on the size of the wound, (ulcer) age and health of the patient.
:> Methodology treatment of dibetic ulcer by idoeagenol .s. leismanol.
1. Clean the wound by saline solution 9%.
2. Remove the necrotic tisuess by Hydrogen Peroxide.
3. Applied Leishmanul solution (I.E.9) three times/aday
2% of the trial group showed transiet hyper-pigmentary changes at the site 0 of original wounds (ulcers). However, these disappeared to wards the end of the study 6 months later.
The initial therapy, showed the high efficiency and quality of idoeugenols (leishmanol) compound in the treatment of diabetic wounds (ulcers) without any side effects noted in the treated patients. 5
Table "A" life table stimates of the incidence (% ) of complete healing over time for study of treatment of diabetic ulcers by (I.E.S) leishmanol, Idoeugenol compound.
0
5
0
Table "B" life table stimates of the incidence (% ) of complete healing over time for study of treatment of septic ulcers by (I .E.S) leishmanol,
35 Idoeugenol compound.
Table "C" life table stimates of the incidence (% ) of complete healing over time for study of treatment of superficial wounds by (I.E.S) leishmanol, Idoeugenol compound.
Bacteriocidal Effects Of Idoeugenol. S. (Leishmanol) Against Cusative Organisms Table "D"
On 3/δept ember/1994 ideugenol sanhory (leishmanol) has been granted a Patent under NO 422.7/8/97 and the application national phase of PCT under the No 422 97 9D. Application inventor (s) Dr. Mohammed Ela eer Babiker δanhory (Ph.D.) Biochemistry V.T.
On 19/March/1998 The Republio of the δudan Ministry of Health General Directorate of pharmacy - the central board of public health. It certificate Idoeugenol Qanhory (liβshmanol) as a drug for the treatment of όutaneous lieshmaniasis and wounds. Under No : δK /02 20052. Under section 13[A] of the regulation, 1974.
On 25/April/1998. Ideugenol. 9. (lishmanol) 17.5%, manufacured as drug for treatment of cutaneous leishmaniasis and wounds mainly diabetic ulcers by GENERAL MEDICINE9 COMPANY LTD. under the licence from δHIN POONG PHARM. CO. LTD .9E0UL, KOREA. Product of DR. Mohamed Elamir Babiker δanhory (Inventor), Tel : 012340354.
On 12 May/1998. Ideugenol. 9. (δaniorra) 1% - 5%, as drug for treatment of acne and acne after shaving manafacured by ALPPO PHARMACEUTICAL INDUδTRIEδ (ALPHA) factoury, al mansource, Aleppo-δyria. Tel : (963) (21)714201/2, Fax :(+)714203. Product of DR. Mohamed Elamir Babiker δanhory, Tel : 012340354.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a compound of Idoeugenol Sanhory I.E.S (leishmanol) C H O I Kl C H OH. as adrug which substantially
S improves the efficiency and quality in treatment of cutaneous leishmaniasis and wounds mainly diabetic ulcers.
It is another object in this invention to provide a compound of ideugenol Sanhory I.E.S (leishmanol) which penetrates and diffuses deep into the affected tissues and reactivate fricarboxylic acid cycle in a series reaction in 0 mitochondria that brings about the catabolism of acetyl residues, liberating hydrogen equivalents which upon oxidation, Lead to the release active oxyen (0 ) which killed amostigate parasite caused (CL) and most of the free energy (ATP) of tissue fuels (CH -CO-S-CoA, active acetate).
* ^ It is also another object in the present invention to provide I.E.δ
(Leishmanol) compound in the process of infiltration into the affected tissues it reactivate cribs cycle which normalized the level of citric acids cycle, mainly, lactic acid CH(OH) COOH, 2.40+03) > (1.80 ± 0.4)
0 PYRORACEMIC ACID, (CH CHO COOH), (0.191 ± 0.0003) > (0.146 ±
0.0003).
Citric acid, [(OH) C H (COOH J], (0.187 ± 0.002) > (0.243 ± 0.0001)
3 2. \£ oxaloacitic acid (HOOCCH(OH) CH COOH), (0.043 ± 0.002) > (0.023 ± 5
0.001) and Glutanic acid (0.025 ± 0.001), {C00H(CH ) CH. (NH ) 0.025
± 0.001} > (0.044 ± 0.001). m mol\1.
It is another object of the present invention to provide. I.E.S (Leishmanol compound which penetrate and diffuses into the affected tissues in reaction 0 to (AMP) cycle which released active oxygen which causes rapture in the Membrane cell of macrophage by oxidation of phospolipds membrane which increased the production of oxygen stimulated in macropage by which amostigate parasite causes cutaneous leishmaniasis to be killed.
5
Which are substituted into the following formula
l OH 1 2°2 I2 - KI- I ,3- C 2 H + H2N -MCI I2 )-CH-COO"
NH3
H 0 ■ H?0 + 0 O O ,'O A Ol (CL.) DISAPPEARED.
It is another object of the present invention to provide that Idoeugenol compound which react with proteins amino acids which releases active nitrogen oxide metabolites into affected tissues which kills the bacteria that cusses the septic wounds.
Which are substituted into the following formula
I.E.S+R HN-CH,-CH2-CH2-CH-COO" NO + HC(VCO,+H,0
It is another object to provide that idoeugenol. s. compound penetrate deep into affective tissues and reacts with (AMP) cycle which realeses active oxygen (O ) by having the affinity to increase with increasing oxygenation of hemoglobin.
Which are substituted into the following formula
E.I.S + AMP + R — ► O + Hb *± R + HbO + Hb(0 ) + Hb(0 )4
2 ^ 2 λ 2'2 ϊ
It is another object to provide that idoeugenol. s. compound (leishmanol) 5 reacted substrates which are catalystically oxidized by the o-o bond in dioxygen or hydrogen peroxide, as peroxidases react hydrogen peroxide.
Which are substituted into the following formula 1 x0w E.I.S+ R+2H 2 O 2 ► R + H 2 O+ O 2
It is another object of the present invention I.E.δ compound (Leishmanol) to deodorizing the affected tissues, Idoeugenol penetrates and defuses deep into the affected tissues which oxidizes hydrogen εulfide to form hydrogen 15 Iodide and active cysteine and liberate sulfur, which is very clear in the yellowish color[medical photo] after the application the drug I.E.δ into affected tissues figure NO. [11/12].
20 Which are substituted into the following formula
alt E.I.S + R + H2S ► = R-2HT+HS-CH2- CH-COO"+S.
25 a st
NH
It is another object in the present invention to provide a new compound Idoeugenol. δanhory (Leishmanol) to illustrate the serious interaction of the above compound (I.E.δ) with tricarboxylic acid cycle in the affected tissues
30 which releases active oxygen (O ), nitrogen oxide (NO), hydrogen iodide
(2HI), as are antiseptic and are antiparsitic, it also produces sulfur as are antifungal agent and also releases, ATP as afree energy of tissue fuels.
5
11
fiKTIFIED SHEET (RULE 91)
Which are substituted into the following formula
ATP
ADP
From the above explanation it can be deduced that Idoeugenol Sanhory compound (Leishmanol) has practically good clinical effects on the treatment of cutaneous leishmaniasis (ulcers), (lesion) and wounds. Mainly diabetic ulcers.
The present invention controls and treats, cutaneous leishmaniasis (CL) which is caused by three species of leishmania L tropica. L. major, L. a ethiopica, also treats, urban cutaneous leishmanias (ACL), venezulensis cutaneous leishmaniasis, defuses cutaneous lieshmaniasis [DCL]. The present invention controls and treats wounds and ulcers , mainly diabetic ulcers, ostemyolitis wounds, bullet wounds, incas wounds, penetrate wound, punctured wound, septic wound, aseptic wound, and also ideugenol is highly effective in superficial wounds.
The present invention also treats and controls other dermatolegical disease, dermatitis artefacta lips, dermatitis artefacta side of face. Insect bites, fungal infection, dermatitis eczema, dermatitis lesions ulcers, and highly effective in the treatment of alopecia areata adult, and acne mainly acne after shaving (Saniorra 1% - 5% ideugenol. 8.). &• hilly effective in treatment of hair dandruff
The compounds of the invention are
The following drawing are illustrative of the invention and are not meant to limit the scope of the invention as encompassed by the claims.
Figure No 1 .a table showing conservation initial substrate redox process [Crips
Cycle] in small animals before and after treatment by Idoeugenol compound [Leishmanol]. 5 Figure No 2. is graph showing the parasiticl examination study group before & after treatment by idoeugenol. s. [Leishmanol]. Figure No 3. a table showing the parasitical examination study group. Figure No 4. a table showing the parasitical examination study group before & after treatment by placebo. Figure 4A. showing [CL] ulcers before & after treatment by idoeugenol
10 compound .s. [Leishmanol]. Figure No 5. showing diabetic ulcers & [CL] before & after treatment by
Idoeugenol. s. compound, [Lieshmanol]. Figure No 6.7.8 showing diabetic ulcers befor & after treatment by Idoeugenol. s compund , [Lieshmanol]. Figure No 9 showing the yellowish color on affected tissues, after application of
15 the Idoeugenol. s, compound [Lieshmanl]. Figure No 10.1 1 are graphs shwing local temperature in the affected tissues, before and after application by Idoeugenol compound [Lieshmanol]. Figure No 12 is a graph showing the parasitical examination study group before
& after treatment by Idoeugenol compound .s. [Lieshmanol]. Figure No 12a Showing amostigate parasite befor & after treatment by 2 Idoeugenol compound [Leishmanol].
Figure No 12b showing rose shape of promostigate parasite before treatment. Figure No 12c Histopathological examination showing amostigate parasite before treatment. Figure No 13 is a graph showing the duration of treatment of cutaneous
Leishmaniasis [in weeks].
25 Figure No 14 showing leishmanol drug manufactured bey General Medicines
Company Ltd. Khartoum Sudan under the licence from Shin Poong Pharm.
Co. Ltd. SD Patent NO. [422]. Dr. M.A.B. Sanhory. Figure No 15 showing treatment of alopecia areatta adult by Idoeugenol .s. compund [Leishmanol], duration 4 weeks. Figure No 16 showing treatment of acne before & after application by Idoeugenol 30 .s. compund [Saniorra. 1 % .5%] manufactured by ALPHA-ALEPPO
Pharmaceutical Industries. Figure No 17 showing application method of anew compound Idoeugenol .S.
[Leismanol]. Figure No 18. a table showing accelerated stability data Idoeugenol .s. -»r [Leishmanol]
DETAILED DESCRIPTION
It has been discovered that this compound penetrates and releases inter tissues (0 ) (2HI) (No) (8), and reactivate (Cribs cycle) and Cycle odinizine
5 monophosfate (AMP) which it release active oxygen against amostigate parasite which causes cutaneous leishmaniasis and also releases nitrogen oxide against bacteria which causes septic wounds (diabetic ulcers) and suppurate sulfur against most of pathogenic fungi. Approximately 98% of patients with cutaneous leishmaniasis and 94%
1 patient with wounds in general [mainly diabetic ulcers] have completely recovered.
MANUFACTURING METHOD OF LEISMANOL SOLUTJON
15 (STANDARD BATCH SIZE : 50.000ml)
1. Formula of manufacturing batch size (50.000 ml)
2. Eugenol (USP) 8.750 Gm
3. Iodine (USP) 1.250 Gm 20 4. Potassium iodide (USP) 1.250 Gm
4. Ethanol (USP) 25.000 ml
5. Purified water (USP) q.s 1.250 Gm
2. manufacturing procedure
25 1) Preparation of eugenol solution dissolve The eugenol within ethanol
2) Preparation of iodine solution dissolve the iodine and potassium iodide with purified water.
3) Preparation of bulk solution
30 mix above eugenol and iodine solution for 30 minutes and make a volume of 50.000ml with purified water and mix.
4) filtering filter above bulk solution with 200-mesh screen.
5) filling and stoppering.
•" fill into plastic bottles and stoppering adjusting the volume
FORMULA OF LEISHMANOL SOLUTION EACH 100ML CONTAINS
eugenol (USP) 17.5Gm iodine (USP) 2.5 Gm potassium iodide (USP) 2.5 Gm ethanol (USP) 50 ml purified water (USP) q.s
Accelerated stability study
product with standing drastic condition.
Procedure
J 5 Samples stored in an oven adjusted at 40c with a beadier containing saturated sodium chloride solution so as to produce relative humidify of approx. 75%
Test interval 0 Samples stored at 40c will be tested monthly for Θ months for the following test:
1. description.
2. assay.
3. leak test 5 4. ethanol content
Comments on accelerated stability
The results attached show that the product is stable under accelerated condition at 40c for 3 months. 0 We can conclude that the product can withstand the atmospheric condition in such acountry like the Sudan for 1 year.
5
Claims
WHAT IS CLAIMED
A method for substantialy treatment of the cutaneous leishmaniasis and septic/aseptic wounds mainly diabetic ulcers ihe range of dosages required to control and treat cutaneous leishmaniasis and wounds in human and animals.
16 βϋ StTTϋTE SHEET (RULE 26)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU50611/99A AU5061199A (en) | 1999-06-03 | 1999-08-09 | Treatment of cutaneous leishmaniasis and other dermatological diseases mainly wounds (diabetic ulcers) by idogenos sanhory |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SD9703/718/91 | 1999-06-03 | ||
| SD7189199 | 1999-06-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2000074691A1 true WO2000074691A1 (en) | 2000-12-14 |
Family
ID=20255914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB1999/001422 WO2000074691A1 (en) | 1999-06-03 | 1999-08-09 | Treatment of cutaneous leishmaniasis and other dermatological diseases mainly wounds (diabetic ulcers) by idogenos sanhory |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2000074691A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005074965A1 (en) * | 2004-02-06 | 2005-08-18 | Vojin Gligovic | Application of natural and synthetic eugenol and essential oils from cloves, pimentos and cinnamon leaves for the prevention and treatment of animal diseases caused by bacteria, fungi and parasites |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1412351A (en) * | 1958-04-04 | 1965-10-01 | New disinfectant | |
| JPH01290608A (en) * | 1988-05-18 | 1989-11-22 | Sunstar Inc | Germicidal composition |
| JPH06199695A (en) * | 1992-03-06 | 1994-07-19 | Yunie:Kk | Agent for amelioration and treatment of diabetes |
-
1999
- 1999-08-09 WO PCT/IB1999/001422 patent/WO2000074691A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1412351A (en) * | 1958-04-04 | 1965-10-01 | New disinfectant | |
| JPH01290608A (en) * | 1988-05-18 | 1989-11-22 | Sunstar Inc | Germicidal composition |
| JPH06199695A (en) * | 1992-03-06 | 1994-07-19 | Yunie:Kk | Agent for amelioration and treatment of diabetes |
Non-Patent Citations (2)
| Title |
|---|
| CHEMICAL ABSTRACTS, vol. 113, no. 7, 13 August 1990, Columbus, Ohio, US; abstract no. 54308, M.KOBAYASHI E.A.: "Microbicidal detergents containing iodine compounds" XP002133590 * |
| DATABASE WPI 1994 Derwent World Patents Index; AN 269371, XP002133591, K.KATO: "Agent for treating diabetes - comprising compounds with SOD or antioxidant activity, phenol and glyco-protein or glycosylated flavonoid" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005074965A1 (en) * | 2004-02-06 | 2005-08-18 | Vojin Gligovic | Application of natural and synthetic eugenol and essential oils from cloves, pimentos and cinnamon leaves for the prevention and treatment of animal diseases caused by bacteria, fungi and parasites |
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