WO2003022260B1 - Use of methotrexate and l-arginine for the preparation of a medicament for treatment of uterine myoma - Google Patents

Use of methotrexate and l-arginine for the preparation of a medicament for treatment of uterine myoma

Info

Publication number
WO2003022260B1
WO2003022260B1 PCT/YU2002/000017 YU0200017W WO03022260B1 WO 2003022260 B1 WO2003022260 B1 WO 2003022260B1 YU 0200017 W YU0200017 W YU 0200017W WO 03022260 B1 WO03022260 B1 WO 03022260B1
Authority
WO
WIPO (PCT)
Prior art keywords
myoma
methotrexate
arginine
mixture
drug
Prior art date
Application number
PCT/YU2002/000017
Other languages
French (fr)
Other versions
WO2003022260A1 (en
Inventor
Slobodan Arsenijevic
Zoran Matovic
Original Assignee
Slobodan Arsenijevic
Zoran Matovic
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 Slobodan Arsenijevic, Zoran Matovic filed Critical Slobodan Arsenijevic
Publication of WO2003022260A1 publication Critical patent/WO2003022260A1/en
Publication of WO2003022260B1 publication Critical patent/WO2003022260B1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183Amino acids, e.g. glycine, EDTA or aspartame
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0034Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

Abstract

The invention illustrates a drug for treatment of myoma of the uterus that enables preservation of biological and sexual properties of the women and does not provoke contraindications accompanying other known methods of treatment. The invention is represented by a mixture of two substances methotrexate and L-arginine. The drug for treatment of myoma of the uterus is composed of 5 g methotrexate and 10 g L-arginine with 985 cm3 water. Combination of two substances in aqueous solution yields a homogenous mixture where each of the components preserves its own chemical identity. The drug is applied on the eighth day of the follicular phase of the menstrual cycle of patients with myoma of the uterus. The patient is placed into lythotomy position, the vaginal speculum is placed and the uterine cervix is pulled with roller forceps so that the external uterine cervix is exposed. The package is open, the puncture needle iS inserted into the cervical channel and is directed to the myometrium towards the side at which myoma is located. The needle is pushed through the endometrium to the depth of 1 cm. It is necessary to be sure to inject the drug at 1 cm depth to avoid possible penetration through the uterine wall. We aspirate to check that the needle is not inside a blood vessel, and after that inject the drug slowly. The syringe and needle are discarded after use. The mixture is applied in three consecutive menstrual cycles. The method is simple, feasible on out-patient basis by practicing gynecologist; no ultrasonografic guidance is needed; transvaginal and transcervical approach is used. The mixture induces the process of apoptosis (programmed cell death) so that no necrosis, degeneration or inflammation are provoked if all antisepsis precautionary measures are applied. Dramatic reduction of both loss of blood during menstruation in women with myoma and the volume of myoma are evidenced. Since the dose applied is very low, toxicity is negligible. Application of this mixture gradually leads to menopause without disturbance of the hypothalamo-pituitary-gonadal axis. Application of this mixture does not provoke early or late complication specific for other medical approaches listed in the background of the invention. After completion of therapy with this medication, the volume of myoma is reduced by 20-30% and no surgical removal is required. After such therapy myoma does not grow any longer. After the therapy menstrual bleedings become normal in volume.

Claims

8AMENDED CLAIMS[Received by the International Bureau on 20 March 2003 (20.03.03): original claims 1-3 modified [1 page]
1. A method for producing aqueous solution of methotrexate (4-amino-N- 10-methyl- pteroilglutamine acid) and of L-arginine (2-amino-5-guanidine-pentane acid), characterized in that, a measured quantity of 10 g of L-arginine in a vessel of 1 dm of volume is added a 600 cm of water, where the vessel is softly shaked until the L-arginine is completely dissolved, after when 5 g of methotrexate is added and vessel softly shaked again until all methotrexate is dissolved, whenafter is in the vessel poured a remnant amount of 360 cm til 390 cm of water, and a so obtained solution than autoclaved in a tandard autoclave.
2. Pharmaceutical preparation made of aqueous solution of a mixture of methotrexate
(4-amino-N- 10-methyl-pteroilglutamine acid) and of L-arginine (2-amino-5- guanidine-pentane acid) obtained by method according to claim 1, characterized in that, in a 985 cm of water is mixed a 5g of methotrexate and 10 g of L-arginine.
3. Use of a methotrexate (4-amino-N- 10-methyl-pteroilglutamine acid) and of L-arginine
(2-amino-5-guanidine-pentane acid) for manufacture of medicine for reduction of volume of myoma uteri.
PCT/YU2002/000017 2001-09-12 2002-09-10 Use of methotrexate and l-arginine for the preparation of a medicament for treatment of uterine myoma WO2003022260A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
YUP-657/01 2001-09-12
YUP065701 2001-09-12

Publications (2)

Publication Number Publication Date
WO2003022260A1 WO2003022260A1 (en) 2003-03-20
WO2003022260B1 true WO2003022260B1 (en) 2003-10-16

Family

ID=25550874

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/YU2002/000017 WO2003022260A1 (en) 2001-09-12 2002-09-10 Use of methotrexate and l-arginine for the preparation of a medicament for treatment of uterine myoma

Country Status (1)

Country Link
WO (1) WO2003022260A1 (en)

Cited By (8)

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US8118728B2 (en) 2000-10-12 2012-02-21 Coloplast A/S Method for implanting an adjustable surgical implant for treating urinary incontinence
US8128554B2 (en) 2000-10-12 2012-03-06 Coloplast A/S System for introducing a pelvic implant
US8157822B2 (en) 2001-03-30 2012-04-17 Coloplast A/S Surgical implant and methods of use
US8215310B2 (en) 2004-05-21 2012-07-10 Coloplast A/S Implant for treatment of vaginal and/or uterine prolapse
US8668635B2 (en) 2000-10-12 2014-03-11 Coloplast A/S Pelvic implant with suspending system
US8920304B2 (en) 2000-07-05 2014-12-30 Coloplast A/S Method and device for treating urinary incontinence
US9005222B2 (en) 2002-08-02 2015-04-14 Coloplast A/S Self-anchoring sling and introducer system
US9186489B2 (en) 2003-03-27 2015-11-17 Coloplast A/S Implantable delivery device system for delivery of a medicament to a bladder

Families Citing this family (1)

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Publication number Priority date Publication date Assignee Title
SI2381932T1 (en) 2009-01-29 2018-12-31 Fondazione Irccs Instituto Nazionale Dei Tumori Intra-cervical device for the release of drugs in the local- regional treatment of cervical cancer

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3513938A1 (en) * 1985-04-18 1986-10-23 Merck Patent Gmbh, 6100 Darmstadt CYTOSTATIC-CONTAINING PHARMACADEPOT
JP2827287B2 (en) * 1988-07-05 1998-11-25 武田薬品工業株式会社 Sustained release microcapsules containing water-soluble drugs

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US9113992B2 (en) 2000-10-12 2015-08-25 Coloplast A/S Apparatus and method for treating urinary incontinence
US8118727B2 (en) 2000-10-12 2012-02-21 Coloplast A/S Method for supporting pelvic anatomy
US8852075B2 (en) 2000-10-12 2014-10-07 Coloplast A/S Pelvic implant systems and methods with expandable anchors
US8162818B2 (en) 2000-10-12 2012-04-24 Coloplast A/S Adjustable surgical implant for pelvic anatomy
US8182413B2 (en) 2000-10-12 2012-05-22 Coloplast A/S Method for fibrous anchoring of a pelvic support
US8182412B2 (en) 2000-10-12 2012-05-22 Coloplast A/S Pelvic implant with fibrous anchor
US8118728B2 (en) 2000-10-12 2012-02-21 Coloplast A/S Method for implanting an adjustable surgical implant for treating urinary incontinence
US8273011B2 (en) 2000-10-12 2012-09-25 Coloplast A/S Adjustable surgical implant and method for treating urinary incontinence
US8449450B2 (en) 2000-10-12 2013-05-28 Coloplast A/S Pass through introducer and sling
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US8574148B2 (en) 2000-10-12 2013-11-05 Coloplast A/S System for introducing soft tissue anchors
US9918817B2 (en) 2000-10-12 2018-03-20 Coloplast A/S Method of post-operatively adjusting a urethral support in treating urinary incontinence of a woman
US8888678B2 (en) 2000-10-12 2014-11-18 Coloplast A/S Pelvic implant with suspending system
US8128554B2 (en) 2000-10-12 2012-03-06 Coloplast A/S System for introducing a pelvic implant
US8668635B2 (en) 2000-10-12 2014-03-11 Coloplast A/S Pelvic implant with suspending system
US8801596B2 (en) 2000-10-12 2014-08-12 Coloplast A/S Sling with support and suspending members formed from same polymer
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US9968430B2 (en) 2000-10-12 2018-05-15 Coloplast A/S Surgical device implantable to treat female urinary incontinence
US9089394B2 (en) 2000-10-12 2015-07-28 Coloplast A/S Pelvic implant with suspending system
US9089396B2 (en) 2000-10-12 2015-07-28 Coloplast A/S Urinary incontinence treatment and devices
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US8123673B2 (en) 2000-10-12 2012-02-28 Coloplast A/S Adjustable surgical implant for treating urinary incontinence
US8932202B2 (en) 2000-10-12 2015-01-13 Coloplast A/S Incontinence implant with soft tissue anchors and length not allowing abdominal wall penetration
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US8157822B2 (en) 2001-03-30 2012-04-17 Coloplast A/S Surgical implant and methods of use
US9943390B2 (en) 2001-03-30 2018-04-17 Coloplast A/S Method of treating pelvic organ prolapse in a female patient by accessing a prolapsed organ trans-vaginally through a vagina
US8603120B2 (en) 2001-03-30 2013-12-10 Coloplast A/S Low mass density surgical implant and methods of use
US9248011B2 (en) 2001-03-30 2016-02-02 Coloplast A/S Surgical implant and methods of use
US9532861B2 (en) 2002-08-02 2017-01-03 Coloplast A/S Self-anchoring sling and introducer system
US9872750B2 (en) 2002-08-02 2018-01-23 Coloplast A/S Self-anchoring sling and introducer system
US9005222B2 (en) 2002-08-02 2015-04-14 Coloplast A/S Self-anchoring sling and introducer system
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