WO1994017046A1 - Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci - Google Patents

Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci Download PDF

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Publication number
WO1994017046A1
WO1994017046A1 PCT/RU1993/000018 RU9300018W WO9417046A1 WO 1994017046 A1 WO1994017046 A1 WO 1994017046A1 RU 9300018 W RU9300018 W RU 9300018W WO 9417046 A1 WO9417046 A1 WO 9417046A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
active substance
treatment
ointment
dioxo
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.)
Ceased
Application number
PCT/RU1993/000018
Other languages
English (en)
Russian (ru)
Inventor
Nikolai Borisovich Leonidov
Nikolai Georgievich Selezenev
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP5016897A external-priority patent/JPH06202872A/ja
Priority to PCT/RU1993/000018 priority Critical patent/WO1994017046A1/fr
Priority to KR1019940703321A priority patent/KR0136999B1/ko
Priority to EP93905681A priority patent/EP0638558A1/fr
Priority to US08/307,654 priority patent/US5543147A/en
Priority to AU36513/93A priority patent/AU669511B2/en
Application filed by Individual filed Critical Individual
Priority to CA002132417A priority patent/CA2132417C/fr
Priority to JP6516897A priority patent/JP2624897B2/ja
Priority claimed from CA002132417A external-priority patent/CA2132417C/fr
Publication of WO1994017046A1 publication Critical patent/WO1994017046A1/fr
Priority to KR1019940703321A priority patent/KR950700889A/ko
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim

Definitions

  • the aforementioned compound finds use in the form of an active substance for a medication for the treatment of wound, radiotherapy, radiotherapy, radiotherapy
  • Ophthalmic ointment is also known, which contains, as a matter of fact, the indicated compound ( ⁇ . ⁇ .Gorupev, Use of methyl acyl in medicine, 1968, Kazan. 7).
  • Indicated ophthalmic ointment is used in the treatment of various species of the eye.
  • the use of this ointment contributes to the healing of rhana, but, in addition to severe burns on the treatment, there is a sharp deterioration of the eyes, which causes a worsening of the incidence of the disease.
  • the invention is also a method of generating a new 15 crystalline connection of a specified connection, which is subject to the exclusion of the exclusion of the exclusion of
  • the inventive medicinal product may be used in any pharmaceutical preparation (medicine, ointment, ointment, candle, suspension).
  • the inventive medicinal product in the form of a suspension of a predominantly active substance in the city of
  • the inventive product in the form of a liniment is a constituent of the active substance in the amount of 4-6 wt.%
  • inventive preparation in the form of an ointment is representative of an active substance in the amount of 1.0-2.5 wt. , and as a pharmaceutical diluent ointment
  • Nov. 30, consisting of a mixture of lanolin and petroleum jelly, at a ratio of 1.0: 1.0-2.5, respectively.
  • inventive medicinal product may be a part of the active material, the declared industrial modifying 2,4-dys-2,4-6-ds-6-ds-6-ds-6-ds-6-ds-6
  • the inventive liniment has a bioavailability that is 30 times greater than that of an ointment on an ointment based on a known known crystalline compound.
  • the claimed 25 drugs in the form of a suspension possesses a high efficient and healing activity and the use of non-derogatory property.
  • the claimed preparation in the form of an ointment is used for the treatment of burns and pains of 30 different types of treatment, especially in the ocular treatment of burns and sores. In this case, the claimed preparation reduces the inflammation of the eyes and injuries of the eye, which accelerates the burns of the eyes.
  • the inventive compound containing a crystalline modification of the indicated compound in combination with the para-aminobenzenesulfamide is detected - 7 - high healing activity in case of difficult healing of infectious diseases (acute ulcer of venous infection, after infection).
  • the terms of healing and use of the claimed product are reduced by 2 to 5 for comparison with the known products.
  • the claimed material is 2,4-dioxo-6-methyl, 2,3,4-thermohydride
  • Tests were conducted in 2 groups for 41 white inferior kryssachi-males weighing 200 + 10 g.
  • the experimental model in the ⁇ th group was linear lengths of 50 mm long. Depending on the used crystalline form, we are testing the connection
  • ⁇ _ —2 1-. 100, s 0 where s_ is the initial area of the city, s; ⁇ - area of the territory on the day of measurement " b, mm ⁇ .
  • the claimed crystalline modification of 2,4-dioxo-15 -6-methyl- ⁇ , 2,3,4-tetrahydropyrimidine is a consumable product, and is
  • the inventive medicinal product may be used in the 20- easy pharmaceutical preparation of a medicinal product (odor, slime, slurry).
  • the claimed drug in the form of a suspension has a high healing active and manifests an unexpected effect of the drug.
  • the medicinal product is 25 vein preparations in the form of a suspension, which preferably contains active substances in the amount of 1.0-2.5 wt. $.
  • the concentration of active substances is explained by the fact that in the indicated interval of concentrations there is a high therapeutic effect, not by any means an accident.
  • Suspension is mixed by mixing. - 17 - ingredients with the creation of a dispersed-heterogeneous system, in a short dispersed phase - a valid substance, and a dispersed medium - a twice-distilled water for an injectable substance.
  • a well-known pharmaceutical diluent is a $ 0.9 water solution for the consumption of liquid or water for injection - 20 will allow the treatment of the product to be carried out.
  • the inventive medicinal product in the form of liniment, according to the invention preferably contains active substances in the amount of $ 5.
  • active substances in the amount of $ 5.
  • any suitable emulsion base was used, for example, oil, complete, free or quick and other. It is predominantly used as a basis for the declared line of quick oil, quick and easy to use food.
  • the vagina was treated with the declared liniment with the indicated content of the active substance.
  • 6 live animals from each series were killed and the study of the composition of the vaginal mucosa was done by visual inspection with
  • the pathogen is the same. After 15 days, it is noted that there is an increase in epithelium on the left arm, the leukemia shaft is decreasing, and there is an increase in the incidence of disease. For 20 days, there is no noticeable focus of failure, the area of non-epithelization
  • 35 leukocyte shaft an extensive current circulating telescope, with a dispensing vessel.
  • Table 7 Comparative dynamics of repressive regeneration at an aseptic rate of inflammation at a rate of 25 and the application of 25 declared declines of oil and excess oil
  • the inventive preparation may also be used as an ointment.
  • the concentration of the active material is determined by the fact that, in the indicated range, the concentration of the signal is very high;
  • the inventive ointment exhibits a high potency and healing activity in the treatment of burns of ⁇ void 35 35 35 different occurrences.
  • the claimed ointment is Fast effective when used in ophthalmic medicine for the treatment of burns and rheumatic eye injuries.
  • the efficacy of the claimed vasodilus in comparison with ointment contains - 27 - a valid material - a known crystalline form of the indicated compound was studied in the experiment in the treatment of eye burns in the eye.
  • Alkaline burns of the eyes of the eye were caused by the introduction of a 3 droplet of a 5 $ -growth solution of the hydroxide (17 sec excision) into the conjunctival sac; then they washed our eyes. 10 The degree of burn was divided after 3 hours, after which treatment began.
  • the claimed ophthalmic ointment containing I mass was used; 2 wt. And 2.5 wt. $ Of active substance; The second series of 15 live (one group) treated with a well-known ointment, containing 2 mass $ of active substance; The 3rd series (I group) was competitive.
  • the inventive ointment containing 2.5 wt. $ Of the active substance 48 72.3 17.4 ° 5 -
  • ⁇ a ⁇ im ⁇ b ⁇ az ⁇ m ⁇ vedennye is ⁇ y ⁇ aniya svide ⁇ els ⁇ - 20 vuyu ⁇ ⁇ ⁇ m, ch ⁇ inventive ointment ⁇ bes ⁇ echivae ⁇ reduction v ⁇ s ⁇ ali ⁇ eln ⁇ g ⁇ ⁇ tsessa and ⁇ ichn ⁇ g ⁇ in ⁇ itsi ⁇ vaniya ⁇ i treatment ⁇ zh ⁇ g ⁇ v eye and ⁇ a ⁇ zhe s ⁇ s ⁇ bs ⁇ vue ⁇ ⁇ anney e ⁇ i ⁇ e- tion of ⁇ g ⁇ vitsy on account usilenn ⁇ y s ⁇ imulyatsii ⁇ tsess ⁇ ⁇ egene ⁇ atsii, ⁇ leds ⁇ viem cheg ⁇ yavlyae ⁇ sya v ⁇ ss ⁇ an ⁇ vlenie 25 ⁇ z ⁇ achn ⁇ s ⁇ i ⁇ g ⁇ vitsy.
  • the use of the claimed appliance was quickly cleaned, decreased and disappeared, and the fire alarm 20 times at the edges of the bed, the pain subsided for 2–3 days, the disruption disappeared.
  • the healing rate was 2 times.
  • the material involved is a new crystalline modification of 2,4-dioxo-6-methyl- ⁇ , 2,3,4-thermohydropyrimidine is used, it is used in the process. 4- ⁇ ag ⁇ d ⁇ i ⁇ imidine
  • the optimal material used in the refrigerant class is liquid nitrogen or liquid carbon dioxide;
  • the specified connection is reached at a temperature of at least 6 ° 0 / minute, resulting in a low
  • the simplest source of material is water and ethanol. With this, the highest yield of the target product is achieved.
  • the claimed material can be independently obtained from the concentration of the original material in the factory.
  • Example II The process is carried out similarly to Example I with a cooling rate of 30 ° C / min. Target product 38.2 wt. $.
  • the resulting material is similar to those of 5 Example I.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une nouvelle modification cristalline de 2,4-dioxo-6-méthyle-1,2,3,4-tétrahydropyrimidine, caractérisée par des distances réticulaires (d) et une intensité relative des réflexes (I). Le procédé d'obtention de ladite substance consiste à utiliser un agent de refroidissement afin de refroidir une solution de 2,4-dioxo-6-méthyle-1,2,3,4-tétrahydropyrimidine dans de l'eau, d'un solvant organique ou d'un mélange des deux, à une vitesse d'au moins 6 °C par minute jusqu'à cristallisation complète de la solution. Ensuite, on retire et on sèche les cristaux obtenus. La substance revendiquée présente des propriétés anti-inflammatoires et stimule la cicatrisation de lésions, elle constitue la substance active dans une préparation utilisée dans le traitement de brûlures et de lésions de divers types.
PCT/RU1993/000018 1993-01-07 1993-01-20 Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci Ceased WO1994017046A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP6516897A JP2624897B2 (ja) 1993-01-20 1993-01-20 ２，４−ジオキソ−６−メチル−１，２，３，４−テトラヒドロピリミジンの結晶変性、その調製方法及びそれに基づく医薬製剤
KR1019940703321A KR0136999B1 (ko) 1993-01-20 1993-01-20 2,4-디옥소-6-메틸-1,2,3,4-테트라히드로피리미딘의 변형 결정체, 이것의 제조방법, 및 이것을 기초로 한 의약제제
EP93905681A EP0638558A1 (fr) 1993-01-07 1993-01-20 Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci
US08/307,654 US5543147A (en) 1993-01-20 1993-01-20 Crystalline modification of 2,4-dioxo-6-methyl-1,2,3,4-tetrahydropyrimidine, a method for the preparation thereof and a medicinal preparation based on it
AU36513/93A AU669511B2 (en) 1993-01-07 1993-01-20 Crystalline modification of 2,4-dioxo-6-methyl-1,2,3,4-tetrahydropyrimidine, method of obtaining the same and a pharmaceutical preparation based on it
PCT/RU1993/000018 WO1994017046A1 (fr) 1993-01-07 1993-01-20 Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci
CA002132417A CA2132417C (fr) 1993-01-07 1993-01-20 Modification cristalline de la 2,4-dioxo-6-methyl-1,2, 3,4-trahydropyrimidine, methode de preparation et preparation m dicale a base de cette molecule
KR1019940703321A KR950700889A (ko) 1993-01-20 1994-09-22 2,4-디옥소-6-메틸-1,2,3,4- 테트라히드록시피리미딘의 변형 결정체, 이것의 제조방법, 및 이것을 기초로 한 의약제제(crystalline modification of 2,4-dioxo-6-methyl-1,2,3,4-tetrahy-dropyrimidine, method of obtaining the same and pharmaceutical preparation based on it)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP5016897A JPH06202872A (ja) 1993-01-07 1993-01-07 オブジェクト指向システム
PCT/RU1993/000018 WO1994017046A1 (fr) 1993-01-07 1993-01-20 Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci
CA002132417A CA2132417C (fr) 1993-01-07 1993-01-20 Modification cristalline de la 2,4-dioxo-6-methyl-1,2, 3,4-trahydropyrimidine, methode de preparation et preparation m dicale a base de cette molecule

Publications (1)

Publication Number Publication Date
WO1994017046A1 true WO1994017046A1 (fr) 1994-08-04

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ID=27169852

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU1993/000018 Ceased WO1994017046A1 (fr) 1993-01-07 1993-01-20 Modification cristalline de 2,4-dioxo-6-methyle-1,2,3,4-tetrahydropyrimidine, son procede d'obtention et preparation pharmaceutique a base de celle-ci

Country Status (1)

Country Link
WO (1) WO1994017046A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU101690A1 (ru) 1952-07-17 1954-11-30 Р.С. Карлинская Способ получени 4-метилурацила
DE3513391A1 (de) * 1982-06-15 1985-12-19 Institut für Pharmakologische Forschung, 1136 Berlin Neues nootropikum

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU101690A1 (ru) 1952-07-17 1954-11-30 Р.С. Карлинская Способ получени 4-метилурацила
DE3513391A1 (de) * 1982-06-15 1985-12-19 Institut für Pharmakologische Forschung, 1136 Berlin Neues nootropikum

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
E.A. EGOROV: "Application of methyluracil in ophthalmology", KAZAN MEDICAL JOURNAL, vol. 4, 1968, pages 71 - 72
G. L. BILICH: "Stimulation of regeneration and defence mechanisms in infantile surgery", 1976, MEDIZINA PUBLISHERS, pages: 31 - 32
M.D. MASHKOVSKY, "Lekarstvennye Sredstva", Posobie po Farmakoterapii Dlya Vrachei, 1986, Izdanie Desyatoe, Tom 2, izd. "Meditsina", M., pages 138-139. *
M.D. MASHKOVSKY: "Pharmaceuticals", vol. 2, 1984, MEDIZINA PUBLISHERS, pages: 138
See also references of EP0638558A4 *

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