Alkaloids indol

1
Lecture ?25

• Alkaloids indols derivatives, purine alkaloids
  and their salts some synthetic analogues
  according to the biological action as substances
  of the medical drugs and components of the dosage
  forms.
• Ass. Medvid I. I.

2
Indole - condensed system of pyrrole and
benzene cycles which have two share
atomsIndole is a structural basis of
physostigmine, strychnine, reserpine alkaloids.
3
Group reaction on indole derivatives Van-Urks
reaction
4

• In the base of reaction is the process of
  electrophyllic substitution. Reagent
  p-dimethylaminobenzaldehyde. Reaction conducts at
  the presence of conc. H2SO4 and FeCl3 as oxidant.
• Derivatives of indole which have free 2 and 3
  positions give this reaction. Reserpine gives
  this reaction by the opening of ring C in the
  presence of acids, as a result position 2 becomes
  free.
• Product of reaction can exist in 2 forms. Color
  of the reaction product depends on the chemical
  structure of primer compounds conditions of the
  reaction. Van-Urks reaction can be hold with
  another aldehyde. So, for reserpine solution of
  vanillin in chloride acid is used.

5
Physostigmine salicylate (Physostigmini
salicylas)Eserini salicylas

• Salicylate of ester of methylcarbaminic acid and
  eseroline or 5-methylcarbaminoiloxy-1,3,1-trimeth
  yl-2,3,2,3-tetrahydropyrrole indole

6
Physostigmine the main alkaloid of calabaric
beans (Faba calabarica) poisonous seeds of West
African plant Physostigma venenosus , Fabaceae
7

• Physical properties
• Physostigmine salicylate - brilliant
  colorless or almost colourless prismatic
  crystals. Soluble in water, easily soluble in
  alcohol, practically insoluble in ether. Aqueous
  solutions are unstable. It melts at about 182 C,
  with decomposition Optic active compound. When
  heated with water easy hydrolyze and therefore
  its solutions for parenteral usage produce in
  aseptic introductions. On the air and light
  product paints in the red color pharmacological
  inactive rubrezerine formed.
• Pharmacological action cased by the
  methylurethane group.
• Proserine - white crystalline powder with
  bitter taste. Very easily soluble in water,
  easily soluble in alcohol and chloroform, ether.
  Hygroscopic. Becomes pink on the light.

8

• Identification of Physostigmine salicylate
• Melting point, the specific rotation.
• Substance gives reaction to salicylates (2
  reactions in SPU).
• Total Pharmacopeial reaction on alkaloids (with
  Dragendorff's reagent)
• After evaporation of the preparation with
  ammonium forms blue residue (physostigmine base),
  which is dissolved in ethanol with formation of a
  blue solution which after the acidification by
  ??3???? becomes red.
• Drug solution in H2SO4 conc. gradually becomes
  yellow.
• Erdman and Frede reagents with medication give
  reddish-yellow color, with HNO3 conc. yellow
  color.

9

• 7. When heated with alkalis (and gradually when
  heated with water) physostigmine salycilate
  hydrolyzed and appears character odor
  methylamine
• 8. At the heating with 0,1 ninhydrine solution
  in conc. H2SO4 on the water bath at 60 0? during
  10 min. And than after cooling solution have
  green fluorescence. Proserine gives blue
  fluorescence at this conditions.
• 9. At the gradually adding to the solution boric
  acid, 0,1 ? solution of nitrate acid and sodium
  nitrite, after 1 min. add sodium hydroxide
  solution, violet color appears.

10
Assay Physostigmine salicylate

• Alkalimetriya, direct titration . The drug is
  dissolved in a mixture of ethanol and chloroform
  and titrated by 0,1 ? N??? to the pink color
  (indicator phenolphthalein). ? ?.m.
• Acidimetry in non-aqueous medium. The drug is
  dissolved in a mixture of chloroform and conc.
  CH3COOH, titrated by 0,1 ? ?Cl?4. For
  determination of the end-point use potentiometry.
  Equivalent point is fixed by potentiometric
  method. ? ?.m./2.
• Complexonometry, reverse titration. As a stable
  titrant acetic-acidic solution of bismuth nitrate
  is used in the presence of potassium iodide.
  Scheme of reaction
• Product of the interaction is filtrated
  and an excess of reagent is titrated by 0,1 ?
  sodium EDTA solution. ? ?.m.

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• STORAGE and USAGE of Physostigmine salicylate
• In an airtight containers of dark
  glass, protected from light. Poison compound.
• Cholinesterase inhibitor, myotic
  mean (atropine antagonist). Used for the
  treatment of glaucoma as 0,25-1 eye drops.
  Introduce subcutaneous 0,1 -1,0 solution the
  neuromuscular diseases (Alzheimer's disease). H.
  d. 0,0005 g, H. d. d. 0,001 g.

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Synthetic substitute of physostigmine Proserine
(Proserinum) Neostigmine methylsulfate

• N-(m-dimethylcarbamoiloxiphenyl)-N,N,N-trimethylam
  monium methylsulfate

13

• Identification of proserine
• Reaction to methylsulfate-ion. If after heating
  the drug with HNO3 conc. add solution of BaCl2,
  white precipitate falls (BaSO4).
• With a solution of iodine preparation forms brown
  sediment of periodide.
• At the heating of drug with alkali dissolution
  of urethane group takes place (m-dimethylaminophen
  ol formed, which is detected by the condensation
  with diazotative sulfanylic acid cherry-red
  color (azo-dyes))

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• Assay
• The modified K'yeldal method. The drug is boiled
  in a K'yeldal flask with NaOH. Dimethylamine,
  which evaporates, distilled with water vapor in
  the receiver with a solution of boric acid.
  Metaborate and tetraborate of dimethylamine
  formed, which are titrated by 0,1 ? solution of
  HCl (mixed indicator). ? ?.m.

16

• STORAGE and USAGE of proserine
• In an airtight containers of dark glass,
  protected from light. Poison compound.
• Substitute of physostigmine.
  Anticholinesterase, antimyasthenic mean. Curare
  antagonist drugs. Used for treatment of
  myasthenia, paralysis, neuritis, atony of
  intestine and urinary bladder, glaucoma, for
  stimulating labor activity as 0,25-1 as eye
  drops.
• Issue tablets 0,015 g, amp. 0,05-1,0.
• H. d., internally 0,015 g, H. d. d.,
  internally 0,05 g H. d. subcutaneous 0,002
  g, H. d. d. s/c 0,006 g.

17
Strychnine nitrate (Strychnini nitras)

• Cycles ??, BD, ED derivatives of indole.
• Cycle ? aromatic and strychnine can be
  nitrated and halogenated.
• N19 tertiary atom, has a base character and
  gives salts with acids.
• N9 is in the lactam group, which may be
  disclosed by the interaction with alcohol
  solution of KOH with formation of carboxyl and
  secondary amino-groups.

18
Strychnine can be found with brucine in the seeds
of tropical plant Strychnos Nux Vomica (emetic
nut)
19
Reserpine (Reserpinum)

11,17-dimethoxy-16-carbmethoxy-18(3,4,5,-trimet
hoxibenzoyloxy)-alloyohimban
20

• Reserpine molecule contains indole (??),
  dihydroquinolysidine (?D),
• partially hydrogenated 3-carbolynic (???),
  hydrogenated isoquinoline (ED) cycles.

Alloyohiban
21
Reserpine contains in the roots of the plant
Rauwolfia serpentina Benth
22

• Physical properties
• Strychnine nitrate - a colorless brilliant
  crystals with very bitter taste. Difficultly
  soluble in water and alcohol, easily soluble in
  boiling water, practically insoluble in ether.
• Reserpine - colorless, white or slightly
  yellow, small crystals or crystalline powder with
  melting point 261-265?. Insoluble in water,
  soluble in chloroform, acetone, pyridine and
  ether, darkening slowly on the exposure to
• light. Optic active compound. At the heating with
  acids or alkalis hydrolysis takes place
  (reserpinic acid, methanol, trimethoxybenzoic
  acid form).

23

• Identification of strychnine nitrate
• Pharmacopeial reaction on alkaloids.
• Solution of the drug in H2SO4 conc. crystal of
  K2Cr2O7 formed the blue-violet strips which
  pass into the red and lilac-green.
• Vitali-Morens reaction. At the interaction with
  HNO3 conc. drug becomes yellow (as opposed to
  brucine, which becomes blood-red) by nitration of
  benzene cycle ? after the evaporation of
  reaction product the residue gives with alcohol
  solution of ??? formed red-violet color.
• Van-Urks reaction (on indole cycles). With 1
  vanillin in glycerol in the presence of H2SO4
  dil. Pink-violet color appears.

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• 5. Reaction on nitrate ions NO3-
• ?) SPU. The interaction with nitrobenzene in the
  presence of sulfate acid
• Quantity of substance, listed in a separate
  article, add to the mixture of 0,1 ml of
  nitrobenzol R and 0,2 ml of sulfate acid R and
  after 5 min. cooled in ice water. Continuing to
  cool slowly and while stirring add 5 ml of water
  R, 5 ml of sodium hydroxide concentrated solution
  R NaOH, 5 ml of acetone R, shake and put for
  standing the apper layer becomes dark purple.
• b) SPU, N. Not discolors potassium permanganate
• The solution of the substance,
  acidified by acid sulfate diluted R H2SO4, not
  discolors solution of 1 g/l potassium
  permanganate R (difference of nitrite ).
• ?) Not pharmacopeial reaction. Interaction with
  iron (??) sulfate FeSO4 in the medium of conc.
  H2SO4 brown ring is formed (FeSO4?NO) (on the
  clock glass )
• 2 Strychnine?NO3 6FeSO4 4H2SO4 2NO
  3Fe2(SO4)3 (Strychnine)2?2SO4 4H2O
• NO Fe2 SO42 ? Fe(NO)SO4

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• d) Unpharmacopeial reaction. Interaction with
  diphenylamine in acidic medium. (conc. H2SO4),
  formed an bright blue organic dye
• diphenylbenzidine
• Sulfimmonium salt of diphenylbenzidine (blue dye)

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• Identification of reserpine
• Specific optical rotation (6 assymetric carbon
  atoms).
• UV-spectroscopy (chromophor groups indole and
  trimethoxybenzoatic acid 2 maximum of
  absorption on UV-spectrum).
• Reactions of indole cycle. With chloric water
  purple, with KMnO4 dark lilac, with vanillin
  in the presence of HCl - pink, with ?2?2
  yellow-lilac color.
• Water solutions of reserpine in UV-light blue
  fluorescence.
• Alcohol solution of the preparation H2SO4
  NaNO2 green fluorescence.

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• With Frede reagent red color, which goes to the
  blue.
• On ester groups
• ?) alkali hydrolysis
• ?) hydroxame sample.
• Van-Urks reaction. With p- dimethylaminobenzaldeh
  yde H2SO4 ??3???? green coloring that goes
  into the red. With vanillin in chloride acid
  pink color.

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Assay

• Strychnine nitrate Alkalimetry, direct
  titration. Titration of the drug in
  alcohol-chloroform solution of 0,1 ? NaOH
  (phenolphthalein indicator).
• ? ?.m.
• Specific additive - brucine.
• Reserpine Acidimetry in non-aqueous medium.
  Hatch is titrated in the medium of anhydrous
  ??3???? by 0,1 ? solution HClO4 (indicator
  crystal violet) to the appearance of green color.
  ? ?.m.

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Storage, usage

• Reserpine
• In airtight containers, in a dark place. Powder
  - poisonous substance.
• Neuroleptic , treatment of hypertension.
  Included in tablets Adelphane (0.1 mg of
  reserpine,10 mg of dihydralasine), Adelphan
  esidrex (Triresid) (Adelfane 10 mg of
  dichlorothiazide), Adelphane esidrex -?
  (Triresid ?)(0,6 g of ??l), Crystepin,
  Neocrystepin. Raunatinethe amount of Rauwolfia
  alkaloids.

• Strychnine nitrate
• In airtight containers. Poison compound.
• CNS stimulant, tonic mean.
• Issue - amp. 0,1-1,0.
• H. d. s/c 0,002 g H. d. d. s/c 0,005 g.

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Alkaloids, purine derivatives Purine condensed
system of pyrimidine and imidazol
If in the core of purine hydrogen atoms in the
pyrimidine nucleus replaced by hydroxyl groups,
we will get xantine
31
Caffeine is contained in coffee beans (Coffea
arabica), tea leaves (Thea sinensis), cola (Cola
acuminata)
32

• Pharmacology
• Caffeine stimulates the central nervous system
  first at the higher levels, resulting in
  increased alertness and wakefulness, faster and
  clearer flow of thought, increased focus, and
  better general body coordination, and later at
  the spinal cord level at higher doses. Once
  inside the body, it has a complex chemistry, and
  acts through several mechanisms as described
  below.
• Metabolism and half-life

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• Theophylline first was isolated from tea leaves
  (Thea sinensis)

• Theobromine is extracted from cocoa beans
  (Theobroma cacao)

34
Three natural alkaloids, derivatives xantine
caffeine, theophylline, theobromine

• Extracted from semi-synthetic uric acid, guanine
  and urea.

35
Very convenient is the method of extraction of
caffeine and theobromine from xantine, which can
be extracted from uric acid (waste poultry farms)
and guanine (fish flakes, waste of paper)

36
Synthesis of caffeine and theophyllin by method
Hmelevskiy - Abramova( firs was synthesed by
Traube in1900 year).
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Caffeine Medications

• Caffeine (??ff??nu?) , Caffeine monohydrate
  (??ff??nu? monohydricum) (SPhU)
• 1,3,7-Trimethyl-3,7-dihydro- 1H-purine-2,6-dione
• 1,3,7-trimethylxantine

• Caffeine-sodium benzoate (Coffeinum-natrii
  benzoas)

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Physical properties

• Caffeine - White or almost white, crystalline
  powder or silky crystals, sublimes readily.
  Moderately soluble
• in water, freely soluble in boiling water,
  slightly soluble in ethanol and ether. Soluble in
  the concentrated solutions of alkali benzoate or
  salicylates. Very weak base, forms unstable salts
  with acids by nitrogen in position 9.

• Caffeine-sodiume benzoate white powder,
  odorless, bitter taste.
• Easily soluble in water, slightly soluble in
  ethanol. Contains 38-40 caffeine.
• Extracted by the mixing and evaporation to the
  dry state of aqueous solutions containing
  equimolar quantity of caffeine and sodium
  benzoate.

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General Pharmacopeial reaction - a reaction on
xantines (Murexide reaction or reaction on purine
alkaloids)
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Identification of caffeine

1. By the physico-chemical constants melting point,
   IR-spectroscopy.
2. With potassium iodide in iodine in the presence
   of HCl dil.- brown precipitate formed(periodide
   ?8?10N4?2J2HJ), which dissolves in NaOH dil.
   solution at the neutralization.
3. Murexide sample.
4. Unpharmacopoeial reaction - with 1 solution of
   tannin white precipitate dissolved in excess of
   reagent.
5. With HgCl2 white crystalline sediment, which is
   a complex compound with the following content
   C5H10N4O2 HgCl2.
6. With acetylacetone and dimethylaminobenzaldehyde.
   Solution of the substance in a mixture of
   acetylacetone and dil. NaOH heated in a water
   bath, cooled, than add solution of
   dimethylaminobenzaldehyde and heat again, cool
   and add water - appears an intense blue color

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Caffeine monohydrate gives all reactions on
caffeine after a preliminary drying at 100-105
C.
42
Identification of caffeine-sodium benzoate

• 1. Caffeine identify by
• a) melting temperature (234-237 C) after
  extraction by chloroform from alkaline solution
• b) Murexide sample
• c) reaction with 1 solution of tannin
• d) reaction with iodine solution
• 2. Sodium benzoate identify by
• e) the reaction with solution of iron (III)
  chloride - pink-yellow sediment
• f) the sodium cation paints the flame in yellow
  color.

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Assay

• Caffeine
• Acidimetry in non-aqueous medium in a mixture of
  acetic acid anhydrous, acetic anhydride and
  toluene, a direct titration. Potentiometric
  indication, the control experiment (??.m).
• Iodometry, reverse titration, indicator - starch
  (??.m/4).
• Cerimetry, reverce titration, with iodometric
  ending. An excess of cerium is neutralized by
  potassium iodide solution. Sodium thiosulfate
  used as titrant. (??.m/4).

• Caffeine-sodium benzoate
• Caffeine content is determined by iodometric
  method (??.m/4). ). In the dry matter it should
  be 38,0 - 40,0 .
• Sodium is determined in the presence of mixed
  indicator (methyl orange solution and methylene
  blue at a ratio of 11) and ether (for the
  extraction of benzoic acid, available in the
  titration) (??.m). Sodium benzoate in the dry
  matter must be not less than 58,0 and not more
  than 62,0 .

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Cerimetric determination of caffeine

• 2 Ce(SO4)2 2 KI ? I2 K2SO4 Ce2(SO4)3
• I2 2 Na2S2O3 ? 2 NaI Na2S4O6

46
Storage, Usage

• Caffeine-sodium benzoate
• In a dry, dark place.
• Central nervous system stimulant, cardiotonic
  mean. Thanks to the solubility in water used in
  the form of injection solutions. Issue - powder,
  tablets 0,1 and 0,2 g, 0,075 g (for children)
  10 ? 20 solutions in amp. by 1,0-2,0 ml.
  Included in the tablets Anaprylline, Pentalgin.

• Caffeine
• In a dry, dark place.
• Central nervous system stimulant, cardiotonic
  mean, at the angiospasms enuresis in children
  stimulant of mental and physical disability,
  poisoning with drugs. Produced as powder.
• Caffeine monohydrate is part of the tablets
  Theophedrine, Cytramone, Cytropak, Askofene,
  Cofficyll, Cophetamine, Benalgin, Coldrex,
  Solpadein, Panadol-??????. Apply in doses by
  0,05-0,1 g as CNS stimulant.

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• Theobromine Theobrominum (SPhU)
• 3,7-Dimethyl-3,7- dihydro-1?-purine-2,6-dione, or
  3,7- dimethylxantine

• Theophylline monohydrate Theophyllinum
  monohydricum (SPhU)
• 1,3-Dimethyl-3,7- dihydro-1?-purine-2,6-dione
  monohydrate, or monohydrate of 1,3-
  dimethylxantine

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Properties

• Theobromine
• White crystalline powder, with bitter taste.
  very slightly soluble in water, ethanol ,ether
  and chloroform slightly soluble in hot water
  easily in dil. Solutions of alkalis and acids.

• Theophylline
• White crystalline powder. Sightly soluble in
  water, ethanol and chloroform easily soluble in
  hot water soluble in dil. Solutions of acids and
  alkalis.

Theobromine and theophylline - amphoteric
compounds with a predominance of acidic
properties (by moving the hydrogen atom at the
nitrogen atom in position 1 or 7).
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Identification of theobromine

1. IR-spectrophotometry.
2. Dissolve the substance in ammonium solution at
   the heating. After cooling add silver nitrate
   solution solution must still be colorless.
   After the boiling during few minutes white
   precipitate formed.
3. Reaction on xantines (murexide sample). At the
   oxidation of theobromine 3-methylalloxane and
   methylurea formed. Ammonium salt of
   dimethylpuepuric acid formed as a result of
   murexide reaction

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• Unpharmacopoeial reactions
• Reaction of the sodium salt of theobromine,
  obtained by the interaction of alkali with an
  excess of preparation, with cobalt (II)chloride
  solution intense violet color appears, which
  quickly disappears, grey-blue precipitate

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1. The reaction of theobromine sodium salt with
   silver nitrate - formed a dense gelatin mass
   (silver salt), which is thinning by heating to
   80 ? and solidifies again at the cooling.
2. With HgCl2 white crystalline precipitate.

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Identification of theophylline

1. Determination of the melting temperature alter
   the drying.
2. IR spectrophotometry.
3. Theophylline in the alkali medium decomposes to
   teophyllidine, which can be identified by the
   reaction of azojoining with diazonium salts, red
   color azo-dye formed.

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1. Determination of the water by semimicromethod (?.
   Fisher) (8-9,5 ).
2. Reaction on xantines (murexide sample). At the
   oxidation of theophylline 1,3-dimethylalloxane
   and urea. Ammonium salt of tetramethylpuepuric
   acid forme as a result of murexide reaction

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1. The reaction of theobromine sodium salt obtained
   by the interaction of alkali with an excess of
   drug, with a solution of cobalt (II) chloride -
   formed white with pink tinge precipitate of
   cobalt salt.
2. With HgCl2 white crystalline precipitate.
3. With alkali solution of sodium nitroprusside
   green color formed dissappears at the adding an
   excess of acid.

55

• The reaction of theobromine sodium salt with
  silver nirate - formed a dense gelatin mass.
• Theophylline with 2,6-dichloroqiunonechloroimide
  in borate
• buffer solution
• (?? 8,5) gives intense blue
• merocyanic dye

56
AssayTheophylline and TheobromineAlkalimetry by
the substituent (indirect alkalimetry).Indicator
phenolphthalein (theobromine) or Bromothymol
blue (theophylline). ? ?.m.
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Storage, usage

• Theophylline
• In airtight containers, place protected
  from light.
• Non-selective phosphodiesterase inhibitor
  (xanthine) treatment of reversible airways
  obstruction. Broncholitic, cardiotonic and
  diuretic mean with moderate influence on the
  stagnation phenomena in the cardiac and renal
  origin organs. Issue powder and tablets by 0,1
  and 0,3 g amp. 2-5,0 candles by 0,2 g. Teopek,
  Theotard, Neophylline, Euphylline. Included in
  tablets Theoephedrine.

• Theobromine
• In airtight containers, place protected from
  light.
• Stimulates the activity of the heart, somewhat
  expands the coronary vessels and bronchi, shows
  diuretic effect. Issue - powder and tablets by
  0,25 g.
• Included in tablets Theminal (with amidopyrine
  and Phenobarbital), Theodibaverine (with
  papaverine and dibazole), Theoephedrine.

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Pentoxifylline (Pentoxifyllinium)Agapurine,
Pentyline, Trental A synthetic analogue of
theobromine

• 3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-7?-purine
  -2,6-dion or 1-(5-oxohexyl)-theobromine

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Identification of pentoxifylline

• Temperature of melting
• IR-spectroscopy
• TLC
• Reaction on xantines
• Formation of azo-dye (look theophylline)
• Assay
• pentoxifylline
• Acidimetry in non-aqueous media in a mixture of
  anhydrous acetic acid and acetic anhydride,
  direct titration. Potentiometric indication.
  (??.m).

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Usage of pentoxifylline

• Has a vasodilator effect, improves tissue oxygen
  supply, decreases thrombosis aggregation and
  reduces blood viscosity. Apply at the peripheral
  circulatory disorders, atherosclerotic disorders,
  ischemic condition after heart attack, in
  ophthalmology, at the hearing disorders. Issue
  tablets of 0,1 g, ampoules of 2-5,0. Adopt
  inside by 0,2 g 3 times daily after meals. In
  the acute disorders of peripheral or cerebral
  circulation injected 0,1 g intravenous in 250-500
  ml of NaCl or 5 glucose solution.

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Synthetic analogues of theophylline

• Theophylline-ethylenediamine (Theophyllinum et
  ethylenediaminum) (SPhU),
• Euphylline (Euphyllinum), Aminophilline

Theophylline
with 1,2-ethylenediamine White, sometimes with
yellowish crystalline powder with slight ammonia
odor. On the air absorbs carbon dioxide, thus
decreasing its solubility. Soluble in water,
aqueous solutions have an alkaline reaction.
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Identification of euphylline

• 1. Theophylline is identified after the
  separation by HCl of ethylenediamine according
  to SPhU
• ?) By the melting temperature of theophylline
  (269 - 274?) after HCl acidification to ?? 4-5
• b) IR-spectroscopy
• c) Reaction of azojoining (look theophylline)
• d) murexide sample.

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• 2. Ethylenediamine can be confirmed by the
  following reactions
• ?) determination of the melting temperature of
  the product of reaction with benzoyl in alkali
  medium (dibenzoylethylenediamine) (SPhU)
• b) with a solution of copper (II) sulfate a
  bright purple color forms
• c) with 2,4-dinitrochlorobenzene yellow
  precipitate falls.

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AssayEuphylline

• Ethylenediamine can be determined by acidimetry,
  indicator methyl orange. ? ?.m./2.
• Ethylenediamine in euphylline should be 13,515
  in the dry matter.
• 2. Theophylline can be determined by
  alkalimetry by substituent 1 after drying in a
  drying cabinet at 25-130 ? to the disappearance
  of amine odor.
• The content of waterless theophylline in
  euphylline should be 84- 87,4 .

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Storage, usage of euphylline

• Given the ability to absorb carbon dioxide,
  stored in a well corked filled to the end
  container, protected from the effects of light
  and moisture.
• Antispasmodic, bronchodilatin, diuretic mean. At
  the bronchial asthma and bronchospasm,
  hypertension, cardiac asthma, to improve blood
  circulation to the brain, decreasing the
  intraperitoneal pressure and brain edema in
  ischemic stroke.
• Used oral by 0,15g after food, i/v (2,4
  solutions by 5,0) and i/m (24 solution by 1
  ml).

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Diprophylline (Diprophyllinum)

• 7-(2',3'-Dioxipropyl)-theophylline

• Less toxic than theophylline. Used for treatment
  of coronary spasm, cardiac and bronchial asthma,
  hypertension. Issue tablets by 0,2 g amp.
  10-5,0 candles by 0,5 g.

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Xantinole nicotinate (Xantinoli nicotinas)
Complamine, Theonicol

• Used to improve peripheral and cerebral
  circulation
• Issue tablets by 0,15 g amp. 15-2,0 ?
  10,0.

• 7-2-oxi-3-(N'-methyl-ß-oxiethylamino)-propyl-t
  heophylline nicotinate

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Thank you for attention!