JPH05500055A - Derivatives of 5-amino-1,2,3,4-tetrahydroacridine and their use as medicines - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] 5-amino-1,2,3,4-tetrahydroacridine derivatives and pharmaceuticals Use of 5-amino-IL 2. s = 4-tetrahydroacridine and the use of these substances as medicines.

The THA molecule, as well as methods for producing this molecule, have already been described in the literature. This product Especially Merck Index No.

8907, named Tacrine in 1st O edition (July 1983) found by the name Depending on the nomenclature applied to write chemical formulas, THA is It can also be said to be 9-amino-1,2,3,4-tetrahydroacridine. .

This molecule apart from its use as an anticholinesterase and respiratory stimulant and Alzheimer's disease, which causes various forms of degeneration, especially severe mental illness in some people. It can be used to treat Ymel's disease. However, treatment with THA until the end Particularly due to the toxicity of some impurities present in available THA preparations, there is a huge shortage. It had a point.

Furthermore, N-substituted derivatives of THA are particularly suitable for p-chlorophenoxyacetate of THA. 1 ~ Salts and para-bromophenoxy acetate salts of THA are known. , these are used to treat pathological conditions caused directly or indirectly by cerebral oxygen deprivation. used (patent for mesoisonal products, French pharmaceutical patent) No. 3860 Specification).

The objectives of the present invention are, on the one hand, low toxicity and, on the other hand, unsubstituted THA THA derivatives with increased specificity and biological activity, especially antitoxicity, compared to It's about offering your body.

The subject of the invention is therefore 5-amino-1,2,3,4-tetrahydroacridine. The following general formula derived from (in the formula, R is A glycosyl group, -thiocarbamyl group, optionally substituted with a purine base, in this case The above groups are common to the two THA molecules bonded via the NH group in the 5-position, -optional an adamantyl group substituted with, -isatinyl group, -α-ketogel aryl group -HJ group, where Z is an ionic form and a monoacyl group that is non-covalently bonded to the molecule of the compound. the residue of a hydrogen atom, in which case the compound is α-adamantane , α-aminoadamantane and adenosine, guanosine or inosine. A small amount of THA that binds to at least one molecule selected from nucleosides. Both exist in the form of a complex with one molecule. ) It is a compound represented by

These compounds can be in the form of racemic mixtures or stereoisomers. Wear.

Compounds in which R is other than a HZ group may also be in the form of pharmaceutically acceptable salts. Wear.

When R represents a glycosyl group, the above group can be an ascorbyl group. . THA ascorbate is water soluble and can be administered intramuscularly (i-m, ), intravenously ( i, v, ) or can be injected subcutaneously or perfused.

When R represents a substituted glycosyl group, said group is an optionally substituted inosinyl group. , adenosinyl or guanosinyl group. I can do it.

When R represents a thiocarbamyl group, the above compound is bis(1,2,3,4-te (trahydro-5-acridinyl)-thiourea.

When R represents an adamantanyl group, the above group is α-adamantanyl or α-adamantanyl. -aminoadamantanyl group.

When R represents a HZ group, the above compound is in the form of a pamoate salt of THA. be able to.

In the present invention, molecules with known drug activity, e.g. antivenom activity, are combined with THA. to increase the effect of THA or its use as a medicine, especially in the practice of administering it. can be easily operated.

These compounds can be prepared using methods known to those skilled in the art, in particular by dissolving THA and other reactants. The THA and other reactants can be simultaneously dissolved in a medium or milled simultaneously in a mortar. I can do it.

Furthermore, the subject of the invention provides that at least one of these compounds or p- Pharmaceutical products containing chlorophenoxyacetate salts, especially for degenerative or atrophic diseases e.g. Treatment of AIDS, dementia, multiple cirrhosis or Dusen myalgia It is a medicine for use.

Another subject of the invention is at least one of the above-mentioned compounds or p-chlorophyllof THA. An effective amount of the phenoxy acetate salt is added to one or more compatible and pharmaceutically acceptable rare It is a pharmaceutical composition containing diluents or auxiliaries.

Such compositions are suitable for treating degenerative or atrophic diseases, especially those of the Alzheimer's type, multiple cirrhosis. , Duchesne, directed to the treatment of myalgia and AIDS. This group Preferably, the compositions are administered orally, parenterally or intravenously.

Furthermore, the present invention provides at least one of the above compounds or p-chlorophenoxylate of THA. By administering cyacetate salts, degenerative or atrophic diseases, especially Alzheimer's Information on how to treat dementia, multiple cirrhosis, Dusen's myalgia and AIDS. It is something that

The routes of administration of such compounds are those commonly used for these treatments, particularly oral, non- Oral or intravenous administration.

The invention will be described and illustrated by the following description and with particular reference to the following drawings: etc., but there are no restrictions.

Figures 1 and 20 show the final results of THA ascorbate and Example 11, respectively. It is a nuclear magnetic resonance (NMR) spectrum diagram of a compound.

Second. 4. 7. 9. 10. II, 13. 15. Figures 17 and 19 Example 1. 2. 4. 5. e, 7. s, 9; described in to and 11 FIG. 2 is an infrared (IR) spectrum diagram of a compound.

Third. 5. 6. 8. 12. 14. Figures 16 and 18 show Example 1. Beckman-D64 spectrophotometry of the compounds described in 2, 3. 4. 7, 8, 9.10 The figure shows an ultraviolet (UV) spectrum obtained with a meter.

Example 1 Preparation and characterization of THA ascorbate (C+J2-NtO-) THA ascorbate Corbate is represented by the following structural formula (1): 2 g of THA base is added to 50 volumes/ Dissolved in 20 ml of vol% ethanol and heated the resulting solution on a water bath for 10 min. The THA was dissolved; the pH of this solution was approximately 10.

At the same time, add 1.80 g of ascorbic acid to 10 mL of a 50% v/v ethanol solution. 1 (pH of solution 2-3).

The two solutions were then mixed and the final pH was 5-7. Two distinctive effects, one On the other hand, there is an exothermic effect, in which heat is generated by mixing the two solutions, and on the other hand, there is a bathochromophore effect, in which both components are The final product was observed to be colorless and yellow or yellowish. Water bath to remove excess solvent Removed and dried on top.

This gives a light yellow microcrystalline powder, which is a mixture of water, alcohol and It was soluble in glycol and had a melting point of 174°C in capillaries.

The elemental analysis of the product obtained was as follows: THA Asco in 1 ml of deuterated water. Obtain the NMR spectrum of the product in C20 by dissolving 10 mg of rubate. The infrared spectrum obtained with VARIAN-60 and shown in Figure 1 is 2 and its ultraviolet spectrum is shown in FIG. 3. This is about 215 r+m, 2 It showed characteristic bands at 45 nm and 320 nm.

Example 2 Production of THAp-chlorophenoxyacetate (C2,N2.N203CI) and characterization THAp-chlorophenoxyacetate can be represented by the following structural formula ([I) Ru: Dissolve 1 g of freshly prepared THA base in 25 ml of absolute ethanol and add slightly Warm; the pH of the solution was 10 at this time. At the same time, 0.94g of p-chlorophene Noxyacetic acid was dissolved in 10 [111] of absolute ethanol (solution pH 4).

The two solutions obtained above are mixed by magnetically stirring and after an exothermic bathochromic reaction, p H was about 7.

The mixture was left overnight and dried on a water bath to remove excess ethanol under vacuum.

This gave a viscous yellow material which slowly crystallized. Compound produced appears in the form of fine, colorless crystals, and the compound is soluble in alcohols and glycols. It had a melting point of 68°C. As a result of the analysis, we obtained the following results: Carbon % 65.54 Hydrogen 96 5.50 Nitrogen % 7.29 Chlorine 96 9.22 The infrared spectrum of the final product compound is shown in Figure 4, and the ultraviolet spectrum is shown in Figure 5. Four characteristics are available at 282 nm, 252 nm, 248 nm and 206 nm. It showed a certain peak.

Example 3 Bis(1,2,3,4-tetrahydro-5-acridinyl)thiourea<czt Preparation and characterization of bis(1,2,3,4-tetrahydro- 5-acridinyl)thiourea can be represented by the following structural formula (III). of THA base in a 150 ml vessel equipped with a cooler and magnetic stirrer. ml of absolute ethanol at low temperature. Warm the solution slightly to reduce all T. HA was dissolved. The mixture was cooled and 5 ml of carbon disulfide was introduced.

The mixture was then stirred with a magnetic stirrer and heated gently for 2 hours. excess The solvent was removed under vacuum on a water bath to obtain a viscous yellow paste and the product was dissolved in alcohol. It was recrystallized in an aqueous solution.

The product obtained was in the form of a yellow microcrystalline powder with a melting point of 268°C. Living The composition was analyzed and the following results were obtained: Carbon% 74.03 Hydrogen % 5.98 Nitrogen % 12.79 Chlorine % 7.32 The UV spectrum is shown in Figure 6, and there are four characteristic peaks at 215 nm, 24 ．． It was observed at 1.5 nm, 324.5 nm and 336.5 na+.

Example 4 Production and characterization of THA Bamoate (C3g+(3°N20g)) THA Bamoate The ate can be represented by the following structural formula ([V): Dissolve 2 g of pamoic acid in 20 ml of 50% aqueous pyridine solution. (pH=5).

At the same time, 2 g of freshly obtained THA base was dissolved in 20 ml of 50% pyridine aqueous solution; The final pH was approximately 1O.

The two solutions were mixed with a magnetic stirrer and a pH of about 6-8 was obtained after an exothermic reaction.

The mixture was then concentrated to dryness on a water bath under vacuum using a water pump.

The product formed is in the form of fine, colorless crystals and is soluble in alcohols and glycols. It had a melting point of 256°C. I analyzed it and got the following results: Carbon 96 73.70 Hydrogen 965.15 Nitrogen % 4.77 The infrared spectrum of the compound is shown in Figure 7 and its UV spectrum is shown in Figure 8, or 209 nm, 238 nm, 289 nm, 302 nm and 3I8 It showed five characteristic peaks at nm.

Example 5 Production and characterization of N-(α-adamantanyl) THA (C2J2@N2) fixed N-(α-adamantanyl)-THA had the following structural formula: 1.08 g of α- Promoadamantanil (molecular weight = 215) in 20ml of absolute ethyl alcohol dissolved in.

1 g of THA base was separately dissolved in 25 ml of absolute ethyl alcohol.

When the two solutions obtained above were mixed by stirring magnetically: the pH changed and heat was generated. A reaction was observed. The reaction was continued for 30 minutes with stirring and then the excess alcohol was removed. The filtrate was removed and dried under vacuum on a water bath. The product was produced as a colorless powder with a yield of about 9596. Obtained in the form of a crystalline powder, the powder is insoluble in water and comparable to alcohols and glycols. It was soluble in both acetone and acetone and had a melting point of 108°C.

I analyzed it and got the following results: Carbon 96 66.88 Hydrogen 96 7.08 Nitrogen % 6.78 The infrared spectrum of this compound is shown in FIG.

Example 6 Production of N-(α-aminoadamantanyl) THA’ (Ct2H31N3) and characterization N-(α-aminoadamantanyl)-THA can be represented by the following structural formula. Ru: 1.18 g of THA hydrochloride was introduced into a 100 ml mortar at low temperature. Then, 0.94 g of α-aminoadamantane hydrochloride was added to a small amount. introduced in small quantities. Mix these two types of powder and pulverize for another 15 minutes at a low temperature. It continued for a while.

The resulting product is a fine, colorless crystalline substance that is soluble in alcohols, glycols, and water. The melting point was 250°C. I analyzed it and got the following results: Carbon % 65.25 Hydrogen 96 7.87 Nitrogen % 9.94 The infrared spectrum of the produced compound is shown in Figure 1O.

Example 7 Production and identification of N-(isatinyl)-THA (C2,H,,N,0.) N-(5-isatinyl)-THA is represented by the following structural formula: The finely ground freshly obtained THAlg was introduced into a 100 ml capacity mortar and then 1 ．． 13 g of 5-bromoisatin were introduced in small portions.

Manual pulverization was maintained for 15 minutes to obtain a fine, deep red microcrystalline powder. obtained The product had a melting point of 140°C and was insoluble in water but soluble in alcohol and glycol. It was soluble in recall and acetone.

I analyzed it and got the following results: Carbon % 59.48 Hydrogen 96 4.8 Nitrogen 96 9.91 The infrared spectrum of this compound is shown in Figure 11, and its UV spectrum is shown in Figure 12. 215.5 nm, 1243.5 nm, 314.5 nm, 319. It showed five characteristic peaks at 5 nm and 320.5 nm.

Adenosine base THA can be represented by the following structural formula: 1.35 g of adenosine Nosine base and 1.18 g of THA hydrochloride hydrate were added as in Examples 6 and 7. It was ground to an extremely fine microcrystalline powder under similar conditions.

The product obtained is a fine, colorless crystalline substance with an alcohol and glycol content. It was soluble in water and had a melting point of 203°C.

Analysis of this compound gave the following results: Carbon 96 55.07 Hydrogen 96 5.62 Nitrogen % 19.55 The generated compound has an infrared spectrum shown in Figure 13 and a UV spectrum shown in Figure 14. It has a spectrum of 212.5 nm, 243.5 nm and 318.5 nm. A characteristic peak was observed at m.

The guanosine base THA can be represented by the following structural formula: Examples 5 and 6 The procedure was performed in the same manner as described in . 1.42g of guanosine base and 1.18g of THA hydrochloride was ground in a mortar.

The product obtained appears as fine, colorless crystals containing alcohols and glycols. It was soluble in water and had a melting point of 208°C.

The analysis yielded the following results: Carbon % 53.38 Hydrogen % 5.45 Nitrogen % 18.95 The infrared spectrum of the obtained compound is shown in Figure 15, and the UV spectrum is shown in Figure 16. As shown in the figure, 207 nm, 240.5 n+n, 315 nm and 317 nm It showed a characteristic peak at nm.

Example IO Inosine base THA can be represented by the structural formula shown below: The procedure was similar to that described in Examples 5 and 6, i.e. 1.18 g of THA Rhodochloride, then gradually add 1.35g of inosine base in a mortar at low temperature. It was ground into a powder and the milling was extended for 15 minutes.

The product obtained is in the form of fine, colorless crystals and is comparable to alcohols and glycols. It was soluble in both water and had a melting point of 216°C.

I analyzed it and got the following results: Carbon % 54.98 Hydrogen % 5.4I Nitrogen % 16.72 The infrared spectrum of the obtained compound is shown in Figure 17, and its UV spectrum is shown in Figure 1. As shown in Figure 8, there are characteristics at 213.5 nm, 243.5 nm and 319.5 nm. It showed a peak.

α-Ketoglutarate can be represented by the following formula: The manufacturing method is as in Example 2. Follow the same method as for producing the compound, and use α-ketoglucose instead of p-chlorophenoxyacetic acid. The mixture of this compound and THA was gradually neutralized using lutaric acid.

After removing excess ethanol, a white viscous product was obtained.

Presented with crystal or microcrystalline powder form deafness. The UV spectrum has a characteristic vane to TH. indicated. The infrared spectrum of the compound finally obtained is shown in Figure 19, and its nuclear magnetic resonance The sound spectrum is shown in Figure 20.

a) Swiss market for acute toxicity of THA ascorbate and THA hydrochloride Expressing THA ascorbate and THA hydrochloride as bases, 20, Intraperitoneal (i, p,) administration in solutions at concentrations of 30, 40, 50 and 60 mg/kg. did.

At doses of 50 mg/kg and 60 mg/kg, the time after administration of the two substances Mortality rate was 100%.

The symptoms are similar for THA and THA ascorbate, and their cholinergic function is similar. Spasticity, convulsions, excessive reflex sensitization to shock and noise, and severe sweating. and salivation.

The rat died of muscle tension and post-mortem clonic muscle spasm was present.

The calculated lethal dose (LD) value is 37 mg for THA hydrochloride (50 mg All died, all survived at 20 rng/kg) and 26 mg for THA ascorbate. Met.

Therefore, the acute toxicity of the above ascorbate is The acute toxicity was greater than that of loride. In both cases the mortality rate is 2 hours after i.p. administration of the substance. observed between.

Conventionally, for humans, the therapeutic dose of THA was 100 to 200 mg/24 hours per person. between 1.6 and 3.2 mg/kg, which is equivalent to LDio ( i, p, ) corresponds to approximately 1/I2. Keeping the same proportions, the dosage will Scorbate is 1 to 2 mg/kg per day for humans and 70 to 140 mg/24 hours. corresponds to

In normal rats, no liver toxicity was found after administration of extremely pure THA. There wasn't.

Furthermore, for comparison purposes, THA hydrochloride or THA as to study the effects of corbate by repeated injections of carbon tetrachloride. The cat developed cirrhosis.

An experiment record 30 Evans, 5-6 months old, weighing 450g and 550g Long rat (Janvier) - Injured animal house (warm) The animals were placed in a room with controlled temperature, humidity, and ventilation, and divided into three groups of 10 animals each.

Next, rats were given 1.25 m of carbon tetrachloride mixed with the same amount of olive oil. g/kg once per day (between 11 a.m. and 11 a.m.) for 4 days. Administered orally.

On days 3 and 4, rats were given 1/2 hour after the third dose of carbon tetrachloride. ) Administered intraperitoneally four times (noon, 8:00 p.m., 8:00 a.m., 4:00 p.m.) - Physiological solution (1 ml/kg (10 rats)) - or THAl in basic form, 5 THA hydrochloride solution (2 mg/kg/m, 1) equivalent to 7 mg (10 animals) of THA ascorbate (2 m g/kg/ml) (10 rats) Neurological score 1 hour after the last i.p. Rats were examined and sacrificed (after weighing) to obtain Researching liver enzymes To do this, the blood sample is loaded onto heparin, and the plasma is quickly separated after centrifugation. was stored until the next day.

The liver was visually observed, fixed in Bouin's solution and hormone calcium, and then microscopically examined. I examined it in the mirror.

Three rats died upon injection of carbon tetrachloride in DI, D2 and D3.

The average weight (g) of the rats before treatment and at the end of treatment is summarized in Table 1.

Table 1: Weight change of rats Control THA THA Hydrochloride ascorbate (8 rats) (9 rats) (9 rats/throat) Before treatment 495 ± 1 0 487 ± 10 491 ± 12 At the end of treatment 464 ± 10 456 ± I2” 453±13$PS: 0.05 - Comparison between before and after treatment according to researcher's test The only difference observed between the three groups was based on carbon tetrachloride liver toxicity, which A weight loss of about 6-8% occurred.

2- Study of the macroscopic appearance of the liver After administration of carbon tetrachloride, steatosis accompanied by cell lysis gradually appeared. At the 48th point, the appearance is opposite. Peach-ochre, almost reddish-brown, characteristic of terrozoa. - Formation of dot-like granular spots throughout the leaf, - In some cases hemorrhagic hematoma.

This does not correspond to alcoholic cirrhosis, but rather to steatohepatitis.

Treatment with THA ascorbate or hydrochloride can cause The view could not be changed significantly.

3-Study of rat behavior and neural activity The following reflexes for each rat are rated as follows: Knee corneal reflex studied in normal 0 None 1 Hibernation One pinna response normal 0 None I For each ear -Grasp reflex normal None O for each front leg 1 Bracing normal 2 reactions 1 leg l Hall all four legs (fall) Upper hall 1 Hole to side one balance test Slope change direction Less than 15 seconds 2 15-30 seconds 1 Greater than 30 seconds 0 Horizontal bar 1~〇 Single flexor reflex normal 1 None〇 1 Spontaneous mobility normal 2 decreased l None 0 The normal score (sum of ratings) was 24 for young rats without any lesions.

Table 2 shows the results obtained with carbon tetrachloride and various treatments.

Table 2: Neurological score ~Rat Carbon Tetrachloride Only (8 rats) -18±1 One carbon tetrachloride + THA (9 rats) -18±l - Ut carbon tetrachloride + THA alcoholate (9 rats) - 18 ± 1 However, in rats, no differences were found between the various treatments for all scores. There is a difference in mobility, this is an optovariometer (ontovarimex) It is quantified by the number of rays of light passing through per minute.

Table 3 Voluntary Mobility of Rats on Niobium Varimeter Mobility of Rats (7 minutes) -Rat carbon tetrachloride only (8 rats) -224±15 -Rat carbon tetrachloride THA (9 rats) 140±16 -Rat carbon tetrachloride + THA ascorbate (9 rats) 229±IO Ne*p≦0.01 - Comparison with rats treated with carbon tetrachloride alone THA There was a very long decrease in motor activity and the rats remained fatigued in the cage. T.H. A ascorbate does not have this effect, but this is probably due to the essence of ascorbate. This is because of its divine stimulating effect.

4- Biological results for plasma The following enzymes were measured: ASAT (aspartate aminotransferase) normal 0.281U/ff 1 ALAT (alanine aminotransferase) normal 0.441υ/iP, 0 J ((alkaline phosphatase) normal 0.69 rU/iGT (glutamine Transferase) Normal 0.4310/I! Biological results are shown in Table 4.

Table 4: Liver enzyme evaluation results ASAT ALAT P, OH8GT -only carbon tetrachloride (8 rats) 224 ± 15 761 ± 212 135 ± 10 6 ± 2-4 salts carbonization +THA (9 rats) 1591±400** 1914±471 146±103 ±1−carbon tetrachloride 10THA ascorbate (9 rats) 680±99 814±144 161±184±1”p <0.05 - "P <O ', 01 carbon chloride injection is transformer It also increases ASAT and ALAT and alkaline phosphatase (POH). I got it. Conversely, it is observed in cases of alcohol sclerosis that GT is There wasn't. This case is therefore relevant to the activity and breakdown of liver cells. of the above test The results showed that THA ascorbate was effective against already damaged liver cells in vivo. It clearly shows that it is less toxic than A.

C) Preliminary study of treatment of AIDS patients with THA ascorbate. Extremely high purity. Ascorbate obtained from THA had very low liver toxicity.

The activity of THA on the cholinergic system was expressed in animals and humans. THA is stiff showed increased choline esterase and increased choline transfer to nerve terminals.

When the same method was applied to THA ascorbate, its effect was found to be retroviral. The situation was even more serious. Its water-soluble dosage form can be administered intravenously and in hospitalized patients. It made Biganryu possible. HIV 1 virus (one of the viruses that causes AIDS) When THA Ascorbe-1 was applied to 20 patients suffering from The number of CD41J cells increased at a significant rate in knee patients with good results. - p24 antigen decreased; Regression of a disease that occurs after a single opportunity.

No liver toxicity was observed in treated patients. THA ascorbate is a cure for AIDS Like THA, it is active at lower doses than THA base, and its water-based As a result of its solubility it can be administered by perfusion, which is a major advantage . As mentioned above, the dosage is 70-140 mg/24 hours.

20 30 40 FIOAn international search report Ippuichi-Aee1ml-k PCT/FR9010063G International Search Report

Claims (16)

[Claims] Derived from 1,5-amino-1,2,3,4-tetrahydroacridine (THA) and the following general formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ (R in the formula is A glycosyl group, monothiocarbamyl group, optionally substituted with a purine base, in this case The above groups are common to two THA molecules bonded via the 5-position NH group, and are optional an adamantyl group substituted with, one isatinyl group, 1a-ketoglutaryl group, -HZ group, where Z is an ionic form and a monoalyte that is non-covalently bonded to the molecule of the compound. Indicates a cid or diacid residue. monohydrogen atom, in which case the compounds are a-adamantane, a-aminoadamantane and and nucleosides such as adenosine, guanosine or inosine. Complexes having at least one molecule of THA bound to at least one molecule It exists in the form of ) A compound characterized by: 2. R is a group other than HZ, and the above compound is in the form of a pharmaceutically acceptable salt The compound according to claim 1, characterized in that 3. characterized in that the above compound is in the form of a racemic mixture or a stereoisomer; The compound according to claim 1 or 2. 4. Claim 1, 2 or 3, characterized in that R is an ascorbyl group compound. 5. R is an optionally substituted inosinyl, adenosyl or guanidocinyl group; 4. A compound according to claim 1, 2 or 3, characterized in that: 6. R is a thiocarbamyl group, and the above compound is a bis(1,2,3,4-tetrahydride Claims 1, 2 or 2 are characterized in that or the compound described in 3. 7. Claims 1, 2, or 2, wherein R is an a-adamantanyl group; 3. The compound described in 3. 8. Claims 1 and 2, characterized in that R is an a-aminoadamantanyl group or the compound described in 3. 9. characterized in that R represents HZ, and the above compound is in the form of a pamoate salt A compound according to claim 1, 2 or 3. 10. At least one of the compounds described in any one of claims 1 to 9 A pharmaceutical product characterized by containing. 11. Containing at least p-chlorophenoxyacetate salt of THA Characteristic medicines. 12. Degenerative or atrophic diseases, especially senile dementia of Alzheimer's type, multiple cirrhosis, dementia Claims 10 and 10 are characterized in that the invention is used for the treatment of myopathy and AIDS. or medicines listed in 11. 13. p-chlorophenoxyacetate salt of THA or claims 1 to 9 an effective amount of at least one of the compounds described in any one of the paragraphs in a compatible and pharmaceutically acceptable manner. A pharmaceutical composition characterized in that it contains in combination with acceptable diluents or auxiliaries. 14. AIDS and degenerative or atrophic diseases, especially senile dementia of Alzheimer's type, Claim 13 characterized in that it is used for the treatment of severe cirrhosis, Dusen's myopathy, etc. Pharmaceutical compositions as described. 15. A claim characterized in that it is used for oral administration, parenteral administration or intravenous administration. The pharmaceutical composition according to claim 13 or 14. 16. Degenerative or atrophic diseases, especially senile dementia of Alzheimer's type, multiple cirrhosis, dementia Any one of claims 1 to 10 in treating Struggle myopathy and AIDS. p-chlorophenoxy of at least one of the compounds described in one section or THA A method for treating the above-mentioned disease, which comprises administering an acetate salt.