CA1044142A - Anti-inflammatory dipeptide - Google Patents
Anti-inflammatory dipeptideInfo
- Publication number
- CA1044142A CA1044142A CA230,772A CA230772A CA1044142A CA 1044142 A CA1044142 A CA 1044142A CA 230772 A CA230772 A CA 230772A CA 1044142 A CA1044142 A CA 1044142A
- Authority
- CA
- Canada
- Prior art keywords
- composition
- dipeptide
- active ingredient
- liquid
- solid form
- 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.)
- Expired
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Abstract of the Disclosure The pharmaceutical composition has a dipeptide or a pharmaceutically-acceptable salt thereof as an active ingredient. The dipeptide has the general formula:
wherein R1 and R2 are the same or different and each is either phenyl or indolyl. The composition may be in a solid form for oral administration in which case the active ingredient is surrounded by an enteric coating.
The composition may also be in a liquid form for admini-stration by injection in which case the active ingredient is dissolved in a physiologically compatible sterile liquid. The composition is useful in the treatment of infiammation in mammals and may be administered daily in an amount of about 40mg of the dipetide or salt per kilogram weight of the mammal.
wherein R1 and R2 are the same or different and each is either phenyl or indolyl. The composition may be in a solid form for oral administration in which case the active ingredient is surrounded by an enteric coating.
The composition may also be in a liquid form for admini-stration by injection in which case the active ingredient is dissolved in a physiologically compatible sterile liquid. The composition is useful in the treatment of infiammation in mammals and may be administered daily in an amount of about 40mg of the dipetide or salt per kilogram weight of the mammal.
Description
The p~esent invention relates generally to pharma~
ceutical compositions useful in the treatment of rheumatism and other disorders involving inflammation and to a method of use thereof. More particularly the invention is concerned with a composition having anti-inflammatory properties and being in a solid form for oral administration or in a liquid form for administration by injection. The composition has as active ingredient a dlpeptide or its pharmaceutically-acceptable salt, which dipeptide has the general formula:
Il 12 lo l H2 7 2 H2N - C - CO.NH - C - COOH
H H
in which Rl and R2 are ~he same or different and each is ; -: .:; ,.
either phenyl or indolyl. When the composition is in a solid form the active ingredient is surrounded by an enteric coating and when the composition is in a liquid form is dissolved in , a physiologically compatible sterile liquid. The invention is also particularly concerned with a method of administra-tion of said composition in the relief or treatment of , rheumatism and other disorders involving inflammation.
Many agents have been proposed for the relief or treat-ment of rheumatism and other disorders involving inflammation but many of them either involve serious toxicity problems or are not very effective anti-inflammatory agents or suffer from both disadvantages.
,~ It has been found that a pharmaceutical composition comprising an enteric coated tablet, capsule, lozenge or pill tj ~ or a solution containing a dipeptide of the formula set out - -above or its pharmaceutically-acceptable salt possesses ; ~ effective anti-inflammatory properties for the relief or .~ .
~7'~ A~
treatment of inflammation and the accompanying swelling in warm-blooded mammals.
For the sake of convenience, the dipeptide present in the pharmaceutical composition of the invention is referred to as "the dipeptide". Each of the amino acids which con-stitute the dipeptide are either phenylalanine or tryptophan.
The amino acids may have either D- or L- stereoisomeric form.
There are therefore sixteen compounds covered by the formula given above, and any form can be used although not al] forms produce identical results. Some dipeptides (especially those containing the L-form) tend to be more quickly metabolized and hence have a shorter biological half life than the dipeptides which contain the amino acids of the D-stereoisomer.
As a result dipeptides containing the L-form are generally effective for a shorter period of time than the dipeptides containing the D-form. Examples of the latter dipeptides are D-phenylalanyl-D-phenylalanine, D-phenylalanyl-D-tryptophan, D-tryptophanyl-D-phenylalanine and D-tryptophanyl-D-tryptophan, all of which resist rapid hydrolysis by mammalian plasma and tissue peptidases with the result that they have a long half life, for example 6 hours or more. -~
Dipeptides which contain L-tryptophan have a double ~
barrelled effect; they are anti-inflammatories before metabo-lism and anti-depressants thereafter. The level of L~
tryptophan in the dipeptide and the quantity of dipeptide - ;
. .
administered can usefully be adjusted according to the level of depression of the patient (as determined on the Hamilton -.~
Depression Scale, Hamilton, M. (1960), J.Neurol Neurosurg.
Physchiat, 23,56). For example, L-tryptophanyl-L-tryptophan ~-can usefully be administered to a severely depressed patient suffering from rheumatoid arthritis. The patient will ex-perience rapid relief from both inflammation and depression :~
ceutical compositions useful in the treatment of rheumatism and other disorders involving inflammation and to a method of use thereof. More particularly the invention is concerned with a composition having anti-inflammatory properties and being in a solid form for oral administration or in a liquid form for administration by injection. The composition has as active ingredient a dlpeptide or its pharmaceutically-acceptable salt, which dipeptide has the general formula:
Il 12 lo l H2 7 2 H2N - C - CO.NH - C - COOH
H H
in which Rl and R2 are ~he same or different and each is ; -: .:; ,.
either phenyl or indolyl. When the composition is in a solid form the active ingredient is surrounded by an enteric coating and when the composition is in a liquid form is dissolved in , a physiologically compatible sterile liquid. The invention is also particularly concerned with a method of administra-tion of said composition in the relief or treatment of , rheumatism and other disorders involving inflammation.
Many agents have been proposed for the relief or treat-ment of rheumatism and other disorders involving inflammation but many of them either involve serious toxicity problems or are not very effective anti-inflammatory agents or suffer from both disadvantages.
,~ It has been found that a pharmaceutical composition comprising an enteric coated tablet, capsule, lozenge or pill tj ~ or a solution containing a dipeptide of the formula set out - -above or its pharmaceutically-acceptable salt possesses ; ~ effective anti-inflammatory properties for the relief or .~ .
~7'~ A~
treatment of inflammation and the accompanying swelling in warm-blooded mammals.
For the sake of convenience, the dipeptide present in the pharmaceutical composition of the invention is referred to as "the dipeptide". Each of the amino acids which con-stitute the dipeptide are either phenylalanine or tryptophan.
The amino acids may have either D- or L- stereoisomeric form.
There are therefore sixteen compounds covered by the formula given above, and any form can be used although not al] forms produce identical results. Some dipeptides (especially those containing the L-form) tend to be more quickly metabolized and hence have a shorter biological half life than the dipeptides which contain the amino acids of the D-stereoisomer.
As a result dipeptides containing the L-form are generally effective for a shorter period of time than the dipeptides containing the D-form. Examples of the latter dipeptides are D-phenylalanyl-D-phenylalanine, D-phenylalanyl-D-tryptophan, D-tryptophanyl-D-phenylalanine and D-tryptophanyl-D-tryptophan, all of which resist rapid hydrolysis by mammalian plasma and tissue peptidases with the result that they have a long half life, for example 6 hours or more. -~
Dipeptides which contain L-tryptophan have a double ~
barrelled effect; they are anti-inflammatories before metabo-lism and anti-depressants thereafter. The level of L~
tryptophan in the dipeptide and the quantity of dipeptide - ;
. .
administered can usefully be adjusted according to the level of depression of the patient (as determined on the Hamilton -.~
Depression Scale, Hamilton, M. (1960), J.Neurol Neurosurg.
Physchiat, 23,56). For example, L-tryptophanyl-L-tryptophan ~-can usefully be administered to a severely depressed patient suffering from rheumatoid arthritis. The patient will ex-perience rapid relief from both inflammation and depression :~
-2-~ ~ ' :, ' . , ~ , ., ,: ~ . ., , ~ . , .
although the relief from inflammation will be more short lived than where the patient is given D-forms of the dipeptide.
A less severely depressed patient might usefully be given a formulation containing a smaller proportion of L-tryptophanyl-L~tryptophan, e.g. a formulation containing 10% down to as little as 1~ of L-tryptophanyl-L-tryptophan based on the total weight of dipeptides present in the formulation. A patient given the latter formulation will experience a lower level of anti-depression activity and more long-lasting relief from inflammation. A patient who is not depressed can usefully be ~
given a formuLation containing only amino acids of the D- , stereoisomeric form. Accordingly, the condition of the patient will dictate which form of dipeptide can most usefully be administered to him.
The dipeptides may be made by conventional methods, for example, by reaction between \ CH2 2 ~ ~
' ~
YHN - C - COX andH2N - C - COOZ
H H
where Y and Z are protective groups that may be removed after ;
completion of the reaction, and X is a halogen atom, e.g.
;~ 20 chlorLnet If the reaction is between two molecules of the same l acid, then Z may ~lso be hydrogen. For example, Y may be the .1 ~
~; carbobenzoxyl radical (C6H5CH2OCO-) and Z may be a methyl group. However, any suitable method used in peptide synthesis may be~employed, for example, generally as described in "The Chemistry of Amino Acids and Proteins" edited by C. L. A.
Schmidt, 2nd edition, 1945, Charles T. Thomas, publisher, ~ Springfield, Illinois, p. 262. -;!
., , _3_ , :
.
.. . .
.,, , , : . :
The term "pharmaceutically-acceptable salt" as used herein includes any salt which is not substantially more toxic than an equal weight of the dipeptide from which it is derived when measured in the same mammalian host using the same vehicle and method of administration. Some examples of such salts are the sodium, potassium, calcium, ammonium and 2 hydroxyethylr ammonium. The preferred salts are the pharmaceutically-accept-able salts with an alkali metal, an alkaline earth metal, ammonia or an amine.
In accordance with the invention, the dipeptide or a pharmaceutically-acceptable salt thereof is formulated into ~ -solid pharmaceutical compositions in dosage unit form for oral administration or into liquid compositions also in dosage unit form for administration by injection. In the former case, the dipeptide or its salt is coated with an enteric substance, i.e.
one which resists dissolution in gastric fluids but disinte-grates and releases the active ingredient in the lntestine.
Enteric substances suitable for the purpose are fats, fatty ~ acids, waxes and mixtures, shellac, ammoniated shellac and cellulose acetate phthalate. Shellac and cellulose acetate phthalate are preferred enteric coating substances.
The dipeptide or its salt is only effective as an anti-inflammatory where it reaches the intestine intact or substan-:
tially intact and the enteric coating is necessary to ensurethat it does so. Should the active ingredient not be protectad by an enteric coating, it will be dissolved by the gastric fluids in the stomach and will be ineffective as an anti-inflammatory. Preferably, as a further protection to the active ngredient, it is combined prior ~o enteric coating with approximately 30% by weight albumin which also resists degra~
~ : : , .: - , ~ , ~ ~; dation in the stomach. - ~ ~
.
,'~ ' ', ~. ~ :
~: :
Formulation of the dipeptide or its pharmaceutically-acceptable salt into a liquid composition involves dispersing the dipeptide or its salt in a liquid which is physiologically compatible sterile and which is a solublizer therefor. A
suitahle liquid i5 distilled water raised to a pH of 12 or .
higher with a base such as sodium hydroxide. After dissolu-tion of the dipeptide or salt, an.acid such as hydrochloric acid can be added to decrease the pH of the resulting solution to about 7.2 at which the solution is suitable for injection. . ~ .
The solid or liquid composition containing the dipep- .
tide or its salt can be formulated in dosage unit form with a pharmaceutical carrier and also, if desired, a suitable addi- :.
tive such as a bacteriostat. Some examples of dosage unit ~ : -forms are tabletsl capsules, lozenges and pills; as well as .:
powders and aqueous and non-aqueous solutions packaged on con- :
tainers either one or some larger number of dosage units and capable of being subdivided into individual doses by suitable measuring devices.
Examples of pharmaceutical carriers suitable for use in .
association with the dipeptide or its pharmaceutically-accept-able salt includes sugars such as lactose and sucrose; starches such as corn starch and potato starch; cellulose derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, methyl -cellulose, and cellulose acetate phthalate; talc; stearic acid;
magnesium stearate; vegetable oils such as peanut oil, cotton- . ~
: seed oil, sesame oil, olive oil, corn oil and oil of theobroma; .-: ~: propylene glycol; glycerine; sorbital; polyethylene glycol;
~; water; agar; alginic acid; isotonic saline; and phosphate buffer solutions; as well as other compatible substances norm-: 30 ally used in pharmaceutical formulations. The compositions of the invention can also contain other components such as color- ' : ing agents, flavoring agents, and/or preservatives. .:.
.', .: ' "
_5~
:, ' . ':
.~,, - . , , . ., .. . : , , ~, , ~ . . , .. ,, .. , . . , ;
, :,, , These materials, if present, are usually used in relatively small amounts. The compositions can, if desired, also contain other therapeutic agents.
The percentage of the dipeptide or its pharmaceutically-acceptable salt in the foregoing composition can be varied within wide limits but for practical purposes it is preferably present in a concentration of at least 5 percent. The most satisfactory compositions are those in which a much higher proportion of said dipeptide or its pharmaceutically-acceptable salt is pxesent. In cases where the composition of the inven-tion is to be administered to humans, it should preferably contain from 25 to 1,000 mg of said dipeptide or its pharma-ceutically-acceptable salt per dosage unit so that the entire ~ amount to be administered during a day can be made up from a `3 reasonable number of dosage units. ;
Also in accordance with the invention, the composition comprising the dipeptide or its pharmaceutically-acceptable salt and a suitable pharmaceutical carrier are employed as an anti-inflammatory agent. To this end they are administered .~ -in dosage unit form for the relief and the treatment of rheu-matism and other disorders involving inflammation. The com-~, position can be administered orally with the dose adjusted to -the needs and tolerances of the individual patients. A suitable daily dose for mammals is about 40 mg/kg., i.e. 40 mg of dipeptide or its salt per kg of patient weight. The composition mayt for example, be packed in a cachet, the cachet body then serving as a;solid carrier. Alternatively, the dipeptide or its pharmaceutically-acceptable salt dissolved in a physio-logically compatible sterile ~olution can be administered ~y 30 ~ injection. Such solutions may contain a thickening agent, for example, methyl cellulose. Thus, for example, a sterile 'I ~ ` .
.1~
',: :: ,' solution of 50 mg of dry sterile dipeptide in powder form dissolved in 10 ml water containing 1% weight by volume methyl cellulose may be prepared and may be packed in sealed containers. The solution, in proper doses, may subsequently be administered by injection.
, ,., i . ,: ' ' "~
~, . , ' .: ' ': ~,'' ' ' ~ ~",' ,''" ' ,' ' '' .' ,: .
'', ~'''''", '~
. . .
. ' .' ::, .
~ ~,~`-.-' ~ ~ '., ''.' : ~ -: . .
- - - .
:~: ' .
: 30 . :~
', ~
~7~ .
, ' :," '
although the relief from inflammation will be more short lived than where the patient is given D-forms of the dipeptide.
A less severely depressed patient might usefully be given a formulation containing a smaller proportion of L-tryptophanyl-L~tryptophan, e.g. a formulation containing 10% down to as little as 1~ of L-tryptophanyl-L-tryptophan based on the total weight of dipeptides present in the formulation. A patient given the latter formulation will experience a lower level of anti-depression activity and more long-lasting relief from inflammation. A patient who is not depressed can usefully be ~
given a formuLation containing only amino acids of the D- , stereoisomeric form. Accordingly, the condition of the patient will dictate which form of dipeptide can most usefully be administered to him.
The dipeptides may be made by conventional methods, for example, by reaction between \ CH2 2 ~ ~
' ~
YHN - C - COX andH2N - C - COOZ
H H
where Y and Z are protective groups that may be removed after ;
completion of the reaction, and X is a halogen atom, e.g.
;~ 20 chlorLnet If the reaction is between two molecules of the same l acid, then Z may ~lso be hydrogen. For example, Y may be the .1 ~
~; carbobenzoxyl radical (C6H5CH2OCO-) and Z may be a methyl group. However, any suitable method used in peptide synthesis may be~employed, for example, generally as described in "The Chemistry of Amino Acids and Proteins" edited by C. L. A.
Schmidt, 2nd edition, 1945, Charles T. Thomas, publisher, ~ Springfield, Illinois, p. 262. -;!
., , _3_ , :
.
.. . .
.,, , , : . :
The term "pharmaceutically-acceptable salt" as used herein includes any salt which is not substantially more toxic than an equal weight of the dipeptide from which it is derived when measured in the same mammalian host using the same vehicle and method of administration. Some examples of such salts are the sodium, potassium, calcium, ammonium and 2 hydroxyethylr ammonium. The preferred salts are the pharmaceutically-accept-able salts with an alkali metal, an alkaline earth metal, ammonia or an amine.
In accordance with the invention, the dipeptide or a pharmaceutically-acceptable salt thereof is formulated into ~ -solid pharmaceutical compositions in dosage unit form for oral administration or into liquid compositions also in dosage unit form for administration by injection. In the former case, the dipeptide or its salt is coated with an enteric substance, i.e.
one which resists dissolution in gastric fluids but disinte-grates and releases the active ingredient in the lntestine.
Enteric substances suitable for the purpose are fats, fatty ~ acids, waxes and mixtures, shellac, ammoniated shellac and cellulose acetate phthalate. Shellac and cellulose acetate phthalate are preferred enteric coating substances.
The dipeptide or its salt is only effective as an anti-inflammatory where it reaches the intestine intact or substan-:
tially intact and the enteric coating is necessary to ensurethat it does so. Should the active ingredient not be protectad by an enteric coating, it will be dissolved by the gastric fluids in the stomach and will be ineffective as an anti-inflammatory. Preferably, as a further protection to the active ngredient, it is combined prior ~o enteric coating with approximately 30% by weight albumin which also resists degra~
~ : : , .: - , ~ , ~ ~; dation in the stomach. - ~ ~
.
,'~ ' ', ~. ~ :
~: :
Formulation of the dipeptide or its pharmaceutically-acceptable salt into a liquid composition involves dispersing the dipeptide or its salt in a liquid which is physiologically compatible sterile and which is a solublizer therefor. A
suitahle liquid i5 distilled water raised to a pH of 12 or .
higher with a base such as sodium hydroxide. After dissolu-tion of the dipeptide or salt, an.acid such as hydrochloric acid can be added to decrease the pH of the resulting solution to about 7.2 at which the solution is suitable for injection. . ~ .
The solid or liquid composition containing the dipep- .
tide or its salt can be formulated in dosage unit form with a pharmaceutical carrier and also, if desired, a suitable addi- :.
tive such as a bacteriostat. Some examples of dosage unit ~ : -forms are tabletsl capsules, lozenges and pills; as well as .:
powders and aqueous and non-aqueous solutions packaged on con- :
tainers either one or some larger number of dosage units and capable of being subdivided into individual doses by suitable measuring devices.
Examples of pharmaceutical carriers suitable for use in .
association with the dipeptide or its pharmaceutically-accept-able salt includes sugars such as lactose and sucrose; starches such as corn starch and potato starch; cellulose derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, methyl -cellulose, and cellulose acetate phthalate; talc; stearic acid;
magnesium stearate; vegetable oils such as peanut oil, cotton- . ~
: seed oil, sesame oil, olive oil, corn oil and oil of theobroma; .-: ~: propylene glycol; glycerine; sorbital; polyethylene glycol;
~; water; agar; alginic acid; isotonic saline; and phosphate buffer solutions; as well as other compatible substances norm-: 30 ally used in pharmaceutical formulations. The compositions of the invention can also contain other components such as color- ' : ing agents, flavoring agents, and/or preservatives. .:.
.', .: ' "
_5~
:, ' . ':
.~,, - . , , . ., .. . : , , ~, , ~ . . , .. ,, .. , . . , ;
, :,, , These materials, if present, are usually used in relatively small amounts. The compositions can, if desired, also contain other therapeutic agents.
The percentage of the dipeptide or its pharmaceutically-acceptable salt in the foregoing composition can be varied within wide limits but for practical purposes it is preferably present in a concentration of at least 5 percent. The most satisfactory compositions are those in which a much higher proportion of said dipeptide or its pharmaceutically-acceptable salt is pxesent. In cases where the composition of the inven-tion is to be administered to humans, it should preferably contain from 25 to 1,000 mg of said dipeptide or its pharma-ceutically-acceptable salt per dosage unit so that the entire ~ amount to be administered during a day can be made up from a `3 reasonable number of dosage units. ;
Also in accordance with the invention, the composition comprising the dipeptide or its pharmaceutically-acceptable salt and a suitable pharmaceutical carrier are employed as an anti-inflammatory agent. To this end they are administered .~ -in dosage unit form for the relief and the treatment of rheu-matism and other disorders involving inflammation. The com-~, position can be administered orally with the dose adjusted to -the needs and tolerances of the individual patients. A suitable daily dose for mammals is about 40 mg/kg., i.e. 40 mg of dipeptide or its salt per kg of patient weight. The composition mayt for example, be packed in a cachet, the cachet body then serving as a;solid carrier. Alternatively, the dipeptide or its pharmaceutically-acceptable salt dissolved in a physio-logically compatible sterile ~olution can be administered ~y 30 ~ injection. Such solutions may contain a thickening agent, for example, methyl cellulose. Thus, for example, a sterile 'I ~ ` .
.1~
',: :: ,' solution of 50 mg of dry sterile dipeptide in powder form dissolved in 10 ml water containing 1% weight by volume methyl cellulose may be prepared and may be packed in sealed containers. The solution, in proper doses, may subsequently be administered by injection.
, ,., i . ,: ' ' "~
~, . , ' .: ' ': ~,'' ' ' ~ ~",' ,''" ' ,' ' '' .' ,: .
'', ~'''''", '~
. . .
. ' .' ::, .
~ ~,~`-.-' ~ ~ '., ''.' : ~ -: . .
- - - .
:~: ' .
: 30 . :~
', ~
~7~ .
, ' :," '
Claims (5)
1. A pharmaceutical composition in a solid form for oral administration or in a liquid form for administration by injection, said composition being useful in the treatment of inflammation and having as active ingredient a dipeptide or a pharmaceutically acceptable salt thereof, said dipeptide having the general formula:
wherein R1 and R2 are the same or different and each is either phenyl or indolyl, said active ingredient when said composi-tion is in a solid form being surrounded by an enteric coating and when said composition is in a liquid form being dissolved in a physiologically compatible sterile liquid, the amount of said active ingregient present in said composition being an amount effective against inflammation.
wherein R1 and R2 are the same or different and each is either phenyl or indolyl, said active ingredient when said composi-tion is in a solid form being surrounded by an enteric coating and when said composition is in a liquid form being dissolved in a physiologically compatible sterile liquid, the amount of said active ingregient present in said composition being an amount effective against inflammation.
2. A pharmaceutical composition in a solid form for oral administration or in a liquid form for administration by injection, said composition being useful in the treatment of inflammation and having as active ingredient a dipeptide or a pharmaceutically-acceptable salt thereof, said dipeptide being selected from the group consisting of D-phenylalanyl-D-phenylalanine, D-phenylalanyl-D-tryptophan, D-tryptophanyl-D-phenylalanine, D-tryptophanyl D-tryptophan, and L-tryptophanyl-L-tryptophan, said active ingredient when said composition is in a solid form being surrounded by an enteric coating and when said composition is in a liquid form being dissolved in a physiologically compatible sterile liquid, the amount of said active ingredient present in said composition being an amount effective against inflammation.
3. The composition as claimed in Claims 1 or 2 wherein said composition is in a solid form and said enteric coating is shellac or cellulose acetate phthalate.
4. The composition as claimed in Claims 1 or 2 wherein said composition is in a liquid form and said sterile liquid is water to which is added a base to cause dissolution of said active ingredient and afterward to which is added an acid to decrease the pH to about 7.2.
5. The composition as claimed in Claims 1 or 2 wherein said composition is in a liquid form and said sterile liquid is water to which is added sodium hydroxide to cause dissolu-tion of said active ingredient and afterward to which is added hydrochloric acid to decrease the pH to about 7.2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA230,772A CA1044142A (en) | 1975-07-04 | 1975-07-04 | Anti-inflammatory dipeptide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA230,772A CA1044142A (en) | 1975-07-04 | 1975-07-04 | Anti-inflammatory dipeptide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1044142A true CA1044142A (en) | 1978-12-12 |
Family
ID=4103533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA230,772A Expired CA1044142A (en) | 1975-07-04 | 1975-07-04 | Anti-inflammatory dipeptide |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1044142A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757151A (en) * | 1985-11-14 | 1988-07-12 | Warner-Lambert Company | 2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl] |
-
1975
- 1975-07-04 CA CA230,772A patent/CA1044142A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757151A (en) * | 1985-11-14 | 1988-07-12 | Warner-Lambert Company | 2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl] |
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