53164-05-9

Basic information

• Product Name: Acemetacin
• Synonyms: ((1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl)acetoxy)aceticacid;(1-(p-chlorbenzoyl)-5-methoxy-2-methylindol-3-acetoxy)essigsaeure;1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1h-indole-3-aceticacicarboxymethyl;1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1h-indole-3-aceticacidcarboxymethyl;2-(2-(1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl)acetoxy)aceticacid;acemetacinum;acemix;aximeixin
• CAS NO: 53164-05-9
• Molecular Formula: C₂₁H₁₈ClNO₆
• Molecular Weight: 415.82
• EINECS: 258-403-4
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;API;EMFLEX
• Mol File: 53164-05-9.mol

Chemical Properties

• Melting Point: 151.5°C
• Boiling Point: 565.5 °C at 760 mmHg
• Flash Point: 295.8 °C
• Appearance: Light yellow solid
• Density: 1.2387 (rough estimate)
• Vapor Pressure: 1.26E-13mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: -20°C Freezer
• Solubility: Practically insoluble in water, soluble in acetone, slightly soluble in anhydrous ethanol.
• PKA: 2.60±0.10(Predicted)
• Merck: 14,27
• CAS DataBase Reference: Acemetacin(CAS DataBase Reference)
• NIST Chemistry Reference: Acemetacin(53164-05-9)
• EPA Substance Registry System: Acemetacin(53164-05-9)

Safety Data

• Hazard Codes: T+
• Statements: 26/27/28
• Safety Statements: 22-25-36/37/39-45-24/25
• RIDADR: UN 2811
• WGK Germany: 3
• RTECS: NL3521400
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 53164-05-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Acemetacin is used as an analgesic and anti-inflammatory agent for the treatment of various conditions such as rheumatoid arthritis, osteoarthritis, and low back pain. It helps alleviate pain and reduce inflammation by inhibiting the COX-2 enzyme, which is responsible for the production of prostaglandins that cause inflammation and pain.
Used in Postoperative Care:
Acemetacin is used as a postoperative analgesic and anti-inflammatory drug to manage pain and inflammation following surgical procedures. Its effectiveness in reducing postoperative pain and inflammation contributes to faster recovery and improved patient outcomes.
Used in Oncology:
Acemetacin is used as an anti-tumor agent, particularly in the treatment of colon cancer. Its anti-tumor activity is attributed to its ability to inhibit the COX-2 enzyme, which plays a role in tumor growth and progression. Additionally, it may have potential synergistic effects when combined with other chemotherapeutic drugs, enhancing their efficacy and chemo-sensitivity in resistant cases.
Used in Drug Delivery Systems:
To improve the bioavailability and therapeutic outcomes of Acemetacin, various drug delivery systems have been developed. These systems, including organic and metallic nanoparticles, serve as carriers for Acemetacin, enhancing its delivery to target tissues and cells, and potentially reducing side effects associated with traditional administration methods.

Originator

Rantudil ,Bayer ,W. Germany ,1980

Manufacturing Process

25.4 g (0.050 mol) of [1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3- indoleacetoxy]-benzyl acetate were dissolved in 400 ml of glacial acetic acid and hydrogenated on 2.0 g of palladium carbon at room temperature. After the absorption of hydrogen had finished (1 hour), the catalyst was filtered off, the filtrate was concentrated by evaporation under vacuum and the compound was caused to crystallize by adding petroleum ether. The compound melted at 149.5-150.5°C (determined on the micro-Kofler bench); the yield was 19.4 g which corresponds to 93% of the theoretical yield. The starting material for the above step may be prepared as follows: 5 g (0.016 mol) of N1-(p-methoxyphenyl)-p-chlorobenzhydrazide hydrochloride and 4.75 g (0.018 mol) of benzyl levulinoyloxyacetate were heated in 25 ml of glacial acetic acid for 3 hours at 80°C. The solvent was then evaporated off under vacuum. The residue was taken up in chloroform and the solution was washed neutral by shaking with sodium bicarbonate solution and thereafter with water. After drying the chloroform solution, this was subjected to chromatography on aluminium oxide, the eluate was concentrated by evaporation and the viscous oil remaining as residue was crystallized by adding ether. The compound melted at 94-95°C. The yield was 4.1 g which corresponds to 50.7% of the theoretical yield.

Therapeutic Function

Antiinflammatory

Safety Profile

Poison by ingestion, subcutaneous,intraperitoneal, intravenous, and intramuscular routes. Anexperimental teratogen. Other experimental reproductiveeffects. When heated to decomposition it emits toxic fumesof Cl?? and NOx. An anti-inflammatory agent.

InChI:InChI=1/C21H18ClNO6/c1-12-16(10-20(26)29-11-19(24)25)17-9-15(28-2)7-8-18(17)23(12)21(27)13-3-5-14(22)6-4-13/h3-9H,10-11H2,1-2H3,(H,24,25)

Synthetic route

acemetacin tert-butyl ester (75302-98-6) → acemetacin (53164-05-9)

Conditions	Yield
With hydrogenchloride; acetic anhydride In acetic acid at 80℃; for 5h; Large scale;	99.45%
With trifluoroacetic acid In dichloromethane at 20℃; for 48h;	80%

2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid tert-butyl ester (1601-20-3) + acetic acid (64-19-7) → acemetacin (53164-05-9)

Conditions	Yield
With hydrogenchloride; aluminum (III) chloride at 60℃; for 5h; Reagent/catalyst; Temperature; Large scale;	98.8%

<1-(4-Chlorbenzoyl)-5-methoxy-2-methylindol-3-acetoxy>essigsaeurebenzylester (53164-04-8) → acemetacin (53164-05-9)

Conditions	Yield
With aluminum (III) chloride In dichloromethane; N,N-dimethyl-formamide at 80℃; for 24h; Temperature;	97.8%
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; under 760.051 Torr; for 20h;	95%
With hydrogen; palladium on activated charcoal In ethyl acetate at 40℃; for 1h;	93%

acemetacin tert-butyl ester (75302-98-6) → [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1) + acemetacin (53164-05-9)

Conditions	Yield
With iodine; aluminium In acetonitrile at 20℃; for 6h; chemoselective reaction;	A 30% B 66%

4-methoxyphenylhydrazine hydrochloride (19501-58-7) → acemetacin (53164-05-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / acetic acid / 1.) 42 h, 28 deg C, 2.) 5 h, 50 deg C 2: 78 percent / various solvent(s) / 3 h / 190 - 195 °C 3: 93 percent / H2 / 5 percent Pd/C / ethyl acetate / 1 h / 40 °C View Scheme

(5-Methoxy-2-methylindol-3-acetoxy)essigsaeurebenzylester (53164-08-2) → acemetacin (53164-05-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / various solvent(s) / 3 h / 190 - 195 °C 2: 93 percent / H2 / 5 percent Pd/C / ethyl acetate / 1 h / 40 °C View Scheme

[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1) → acemetacin (53164-05-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) DMF, 45 min, 50 deg C, 2.) 3 h, 50 deg C 2: 93 percent / H2 / 5 percent Pd/C / ethyl acetate / 1 h / 40 °C View Scheme

levulinic acid (123-76-2) + phosphorus pentasulfide → acemetacin (53164-05-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) K2CO3 / 1.) DMF, 70 min, 40 deg C, 2.) 4 h, 50 deg C 2: 80 percent / acetic acid / 1.) 42 h, 28 deg C, 2.) 5 h, 50 deg C 3: 78 percent / various solvent(s) / 3 h / 190 - 195 °C 4: 93 percent / H2 / 5 percent Pd/C / ethyl acetate / 1 h / 40 °C View Scheme

Laevulinoyloxyessigsaeurebenzylester (53164-03-7) → acemetacin (53164-05-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / acetic acid / 1.) 42 h, 28 deg C, 2.) 5 h, 50 deg C 2: 78 percent / various solvent(s) / 3 h / 190 - 195 °C 3: 93 percent / H2 / 5 percent Pd/C / ethyl acetate / 1 h / 40 °C View Scheme

4-Methoxyphenylhydrazin-β-sulfonsaeure Natriumsalz → acemetacin (53164-05-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 68 percent / conc. HCl / H2O / 2 h / 20 °C 2: 80 percent / acetic acid / 1.) 42 h, 28 deg C, 2.) 5 h, 50 deg C 3: 78 percent / various solvent(s) / 3 h / 190 - 195 °C 4: 93 percent / H2 / 5 percent Pd/C / ethyl acetate / 1 h / 40 °C View Scheme

N-methyl-N-(2-nitrooxyethyl)ammonium nitrate (145459-16-1) + acemetacin (53164-05-9) → (N-methyl-N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate (646511-41-3)

Conditions	Yield
With 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; dmap; triethylamine In dichloromethane at 20℃;	85%

2-nitroxyethylammonium nitrate (4665-58-1) + acemetacin (53164-05-9) → (N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate (646511-43-5)

Conditions	Yield
With 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; 2-(Dimethylamino)pyridine	60%

{(1R,2R)-cyclohexane-1,2-diamine}dichloridoplatinum(II) (38780-40-4, 52691-24-4, 61848-70-2, 61848-66-6, 61848-62-2) + acemetacin (53164-05-9) → C27H31Cl2N3O6Pt

Conditions	Yield
With sodium carbonate; silver nitrate In N,N-dimethyl-formamide at 20℃; for 24h; Darkness;	53%

methanol (67-56-1) + acemetacin (53164-05-9) → 2-methoxy-2-oxoethyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate

Conditions	Yield
With tert.-butylnitrite at 40℃; for 48h; Green chemistry;	48%

acemetacin (53164-05-9) + rubitecan (91421-42-0) → acemetacin

Conditions	Yield
With dicyclohexyl-carbodiimide; dmap In DMF (N,N-dimethyl-formamide) at 20℃; for 96h;	32%

acemetacin (53164-05-9) → 2-(4-Chlorphenyl)-6-methoxy-4H-3.1-benzoxazinon-4 + N-(4-Chlor-benzoyl)-5-methoxy-anthranilsaeuremethylester + <2-(4-Chlor-benzoylamino)-5-methoxy>-benzoyl-2-essigsaeuremethylester + <2-(4-Chlor-benzoylamino)-5-methoxy>-benzoyl-2-acetoxy-essigsaeure

Conditions	Yield
With oxygen; methylene blue In methanol for 10h; Irradiation; Further byproducts given;	A 24% B 21% C 11% D 21%

acemetacin (53164-05-9) → 2-Acetyl-N-(4-chlor-benzoyl)-4-methoxy-anilin + N-(4-Chlor-benzoyl)-5-methoxy-anthranilsaeuremethylester + <2-(4-Chlor-benzoylamino)-5-methoxy>-benzoyl-2-essigsaeuremethylester + <2-(4-Chlor-benzoylamino)-5-methoxy>-benzoyl-2-acetoxy-essigsaeure

Conditions	Yield
With oxygen; methylene blue In methanol for 10h; Irradiation; Further byproducts given;	A 10% B 21% C 11% D 21%

acemetacin (53164-05-9) → 5-methoxy-2-methylindol-3-yl acetic acid carboxymethyl ester + para-chlorobenzoic acid (74-11-3)

Conditions	Yield
With sodium hydroxide at 30℃; Kinetics; Equilibrium constant; Further Variations:; Solvents; detergents; micelles; zwitterionic micelles;
With borate buffer at 30℃; pH=9.65; Kinetics; Equilibrium constant; Further Variations:; with/without L-α-phosphatidylcholine vesicles; detergents; micelles;
With perchloric acid In water at 25℃; Kinetics; Product distribution;

acemetacin (53164-05-9) → 5-Methoxy-2-methylindole-3-acetic acid (2882-15-7) + [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1) + 5-methoxy-2-methylindol-3-yl acetic acid carboxymethyl ester + para-chlorobenzoic acid (74-11-3)

Conditions	Yield
In water at 30℃; Kinetics; Further Variations:; pH-values; Temperatures;

acemetacin (53164-05-9) → 4-chloro-N-hydroxybenzamide (1613-88-3)

Conditions	Yield
Stage #1: acemetacin With sodium hydroxide; hydroxylamine hydrochloride Stage #2: With hydrogenchloride; iron(III) chloride

Cu2(CH3COO)4(H2O)2 + acemetacin (53164-05-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → bis(N,N-dimethylformamide)bis-(O,O'-ACM)copper(II) + bis(N,N-dimethylformamide)tetrakis-μ-(O,O'-ACM)dicopper(II)

Conditions	Yield
at 20 - 35℃;

1H-imidazole (288-32-4) + Cu2(CH3COO)4(H2O)2 + acemetacin (53164-05-9) → bis(O,O'-acemetacin)bis(imidazole)copper(II)

Conditions	Yield
In methanol; water for 0.416667h;

zinc diacetate (557-34-6) + water (7732-18-5) + acemetacin (53164-05-9) → bis(O,O'-acemetacin)diaquzinc(II)

Conditions	Yield
In ethanol at 60℃;

Cu2(CH3COO)4(H2O)2 + water (7732-18-5) + acemetacin (53164-05-9) → bis(O,O'-acemetacin)diaquacopper(II)

Conditions	Yield
In ethanol at 20 - 40℃;

[Co(NH3)5(OSO2CF3)](CF3SO3)2 + acemetacin (53164-05-9) → pentaammine(acemetacin)cobalt(III) bis(trifluoromethanesuIfonate)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 50 - 80℃; for 5h;

1,2,3,4-tetra-O-trimethylsilyl-β-D-glucopyranose (98461-21-3) + acemetacin (53164-05-9) → C39H60ClNO11Si4

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 5h;

Duloxetine (116539-58-3, 116539-59-4, 116539-60-7, 116817-13-1) + acemetacin (53164-05-9) → acemetacin (S)-duloxetine salt (1309349-71-0)

Conditions	Yield
Stage #1: Duloxetine; acemetacin In tetrahydrofuran; methanol Stage #2: In di-isopropyl ether at 12℃; for 12h;
In tetrahydrofuran; methanol Product distribution / selectivity;

Upstream product

• 53164-04-8 <1-(4-Chlorbenzoyl)-5-methoxy-2-methylindol-3-acetoxy>essigsaeurebenzylester 
• 19501-58-7 4-methoxyphenylhydrazine hydrochloride 
• 1601-20-3 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid tert-butyl ester 
• 64-19-7 acetic acid 
• 75302-98-6 acemetacin tert-butyl ester 
• 53164-03-7 Laevulinoyloxyessigsaeurebenzylester 
• 123-76-2 levulinic acid 
• 53-86-1 [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid 
• 53164-08-2 (5-Methoxy-2-methylindol-3-acetoxy)essigsaeurebenzylester 

Downstream Products

• 75511-23-8 5-methoxy-2-methylindol-3-yl acetic acid carboxymethyl ester 
• 74-11-3 para-chlorobenzoic acid 
• 2882-15-7 5-Methoxy-2-methylindole-3-acetic acid 
• 53-86-1 [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid 
• 1613-88-3 4-chloro-N-hydroxybenzamide 
• 646511-43-5 (N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate 
• 1309349-71-0 acemetacin (S)-duloxetine salt 

Relevant articles and documents

Preparation method of acemetacin

The invention discloses a preparation method of acemetacin. The preparation method comprises the following steps: (1) introducing hydrogen chloride into glacial acetic acid to prepare an acetic acid solution of hydrogen chloride; (2) adding acetic anhydride into the acetic acid solution of hydrogen chloride prepared in the step (1); (3) adding acemetacin tert-butyl ester into the hydrogen chloride-acetic acid-acetic anhydride mixed acidolysis solution obtained in the step (2), and stirring at a constant temperature; (4) after the reaction is finished, cooling, carrying out standing crystallization, filtering, and carrying out top-washing to obtain a crude product acemetacin; and (5) refining the crude product acemetacin to obtain the finished product acemetacin. The invention provides a preparation method of acemetacin, wherein the influence of moisture in raw materials on an acidolysis reaction of acemetacin tert-butyl ester is eliminated on the premise of adopting the existing equipment, so that the product yield is increased, the production cost is lowered, and the economic benefit is improved.

Preparation method of acemetacin

The invention discloses a synthesis method of acemetacin. The synthesis method includes the steps that A, acemetacin benzyl ester is prepared according to the patent US4600783; B, the acemetacin benzyl ester is dissolved in a solvent, wherein the solvent is one of acetonitrile, methylbenzene and dichloromethane, a benzyl kation scavenging agent is added, the scavenging agent is one of anisole, phenol and N,N-dimethylaniline, and a solution A is obtained; C, aluminum chloride is added into the solvent, the prepared solution A is added at zero temperature, and the materials are stirred at normaltemperature; D, after the reaction is completed, a reaction mixture is poured into ice water, the materials are stirred and then filtered, and crude acemetacin is obtained; E, the obtained crude acemetacin is recrystallized according to the volume ratio of acetone to water being 2:1, vacuum drying is carried out, and the pure acemetacin is obtained. The method is easy to carry out, easy and convenient to operate and suitable for large-scale preparation, the price of aluminum chloride is low, no dechlorinated byproducts are generated, the purity of the acemetacin can reach and be larger than 99.8% only through one step of simple recrystallization, and no heavy metal residues are generated.

Chemoselective ester/ether C–O cleavage of methyl anisates by aluminum triiodide

The aluminum triiodide mediated chemoselective ester/ether C–O cleavage of methyl anisates was investigated. o-Anisate undergoes ether cleavage at low temperatures in carbon disulfide, cyclohexane and acetonitrile. Further cleavage of the ester group occurs at elevated temperatures to afford salicylic acid. The cleavage of p-anisate is solvent-dependent. In cyclohexane, the ester and ether groups were cleaved non-selectively to give equimolar amounts of p-anisic acid and methyl p-hydroxybenzoate. The ester group was preferentially cleaved in acetonitrile, compared to ether group cleavage in carbon disulfide. The ester cleavage reaction was improved using pyridine as an acid scavenger additive. Reasons for the contrasting reactivity of anisates towards AlI3 were explored, and the methods were applied to cleavage of the tert-butyl ester of acemetacin which gave different products under these conditions.

Preparation method for acemetacin

The invention relates to a preparation method for an anti-inflammatory and anti-phlogistic analgesic medicament, in particular to a preparation method for acemetacin, and belongs to the technical field of chemical pharmacy. The method comprises the following steps: introducing hydrogen chloride into acetic acid to prepare acetic acid and hydrogen chloride acidolysis solution, adding acemetacin tert-butyl ester into the acidolysis solution, stirring at a constant temperature, performing an acid hydrolysis reaction, cooling after the reaction is ended, standing, crystallizing, filtering, performing top washing, and refining to obtain the finished product acemetacin.

Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats

The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.

Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use related applications

The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

Process for the preparation of alkenyl esters of acemetacin

The new indole derivatives of the formula STR1 in which R1 and R2 are identical or different and denote hydrogen or lower alkyl, R3 denotes hydrogen, lower alkyl or halogen and R4 and R5 are identical or different and denote hydrogen, lower alkyl or optionally substituted aryl, and R4 and R5 can also represent lower alkenyl, and wherein R2 and R5 can be linked by an alkylene bridge of the formula in which n represents the number 0 or 1, can be prepared by reacting an ammonium or phosphonium salt of the corresponding indolecarboxylic acid with a haloacetic acid allyl ester. The new compounds can be used to prepare acemetacin. The new indole derivatives possess a pharmacological action.

Preparation process of acemetacin

A process for preparing acemetacin which process comprises removing a protecting group, which is other than tetrahydropyranyl group and is removable under acidic conditions, from an acemetacin ester represented by the formula STR1 wherein R means the protecting group, under the acidic conditions.

Process for preparing acemetacin

Acemetacin is prepared by reaction of an indometacin with tert.-butyl halogenoacetate and subsequent cleavage with sulphuric acid and/or sulphonic acid.

Isobutylene polymer active compound release systems

In a therapeutic system such as a plaster for administration of an active compound through the skin and comprising a covering layer which is essentially impermeable to the active compound an active compound reservoir layer and a protective layer which can be pulled off and which is essentially impermeable to the active compound, the improvement wherein the reservoir layer contains about 1-30% of active compound in an elastomer mixture comprising at least one of polyisobutylene, polybutadiene oil and paraffin oil, and a tackifying resin. Thereby the active compound can be released in regulated relatively large quantity over a prolonged period of time.