FR2464943A1 - ALUMINUM SALTS OF N-ACYLCARNOSINE, THEIR PREPARATION AND THEIR APPLICATION IN THE TREATMENT OF DIGESTIVE TRACT ULCERS - Google Patents

Abstract

THE SUBJECT OF THE INVENTION IS AN ALUMINUM SALT OF N-ACYLCARNOSINE. THIS SALT MEETS THE FORMULA: (CF DRAWING IN BOPI) IN WHICH RALKYL LOWER IN CC, PHENYL OR PHENYL SUBSTITUTED BY ALCOXY LOWER, L1 A 5, M1 A 3 AND N0 A 8. PREPARATION OF ORAL OR INJECTABLE MEDICINES TO TREAT ULCES PEPTICS AND OTHER ULCERS OF THE DIGESTIVE TRACT.

Description

!

  The present invention relates to aluminum salts of N-acylcar-

  nosine, their preparation and a medicine against the ulcers of the digestive tract.

containing such salt.

  In recent years, there has been a clear trend towards increasing the number of patients suffering from a gastrointestinal ulcer or a peptic ulcer, and it has obviously been sought to

  drugs against ulcers of this kind.

  The Applicant has synthesized a number of compounds and has

  their pharmaceutical effects. As a result of this research, it has

  that the compounds of N-acylcarnosine of a particular type, which will be described later, show an excellent effect against ulcers of the digestive tract or an anti-ulcerative action and that, moreover, these compounds are of low toxicity and are therefore satisfactory for use

  Medical. Based on these findings, the present invention has been

borated.

  Accordingly, the main objects of the invention are to provide: - aluminum salts of N-acylcarnosine of a new type; - a new process for the preparation of these aluminum salts of N-acylcarnosine and - a new drug - for the treatment of ulcers of the digestive tract which

  comprises an effective dose of an aluminum salt of N-acylcarnosine.

  Briefly, the above-mentioned objectives, as well as others, are attained if an aluminum salt of N-acylcarnosine corresponding to the formula (I) CH 2 CHCOO AQm (OH) n is used.

HN - N (I)

HNN NHCOCH2CH2NHCOR (

  Wherein R represents a lower alkyl radical of 1 to 6 carbon atoms, a phenyl radical or a phenyl radical substituted by a lower alkoxy group, 2 is an integer of 1 to 5, m is an integer of

  1 to 3 and n is 0 or an integer of 1 to 8.

  The aluminum salts of N-acylcarnosine of formula (I), according to

  the invention can be prepared for example by the reaction of an N-

acylcarnosine of formula (II).

  Wherein R has the same meaning as above with an aluminum alkoxide or an aluminum mineral salt according to any one of the methods of the present invention.

described below.

  Process 1 An N-acylcarnosine is reacted with an aluminum alkoxide

  and thus an aluminum salt of N-acylcarnosine of formula (I) is obtained.

  For example, N-acylcarnosine can be prepared for use in

  quality of one of the starting materials, by converting the carboxylic acid

  that corresponding to an acid halide in a usual manner and then by reacting this halide with carnosine. Carnosine which can be used as a starting material for the preparation of Nacylcarnosine can be

in the form L, D or DL.

  As representative examples of aluminum alkoxide, it is possible to

  mention in particular the methylate, the ethylate, the isopropylate, the aluminum t-butylate

  as well as aluminum cyclohexylate and similar compounds. Lors-

  If the aluminum alkoxide contains any impurity, such as aluminum hydroxide or a polymer thereof, it is preferable to remove this impurity by distillation, extraction with a solvent or the like. The reaction is advantageously carried out in a suitable solvent and at a temperature between room temperature and C. The appropriate solvents are water, organic solvents such as

  methanol, ethanol, isopropanol or butanol and mixtures thereof.

  Once the reaction is complete, the reaction solution is removed from the alcohols produced on a secondary basis and the aluminum salt is thus obtained.

  desired N-acylcarnosine of formula (I).

  Process 2 An N-acylcarnosine is reacted with a mineral salt of aluminum and the resulting aqueous reaction solution is passed through a column packed with an anion exchange resin and thus the salt is obtained.

  desired aluminum N-acylcarnosine of formula (I).

  As representative examples of the inorganic salts of aluminum that may be used in this method 2, mention may be made of the salts of mineral acids

  aluminum such as sulphate, nitrate or aluminum chloride.

  The anion exchange resin useful in process 2 may be a weakly basic resin or a strongly basic resin, and yet an anion exchange resin of the weakly basic type such as

  for example the product "Amberlite IR 45".

  The amount of anion exchange resin to be used depends on the amount of the mineral acid ions and the type of ions present in the aqueous solution containing the N-acylcarnosine and the mineral acid. Too small proportions of such a resin cause the introduction of acid ions

  in the effluent, while high proportions of resin pro-

  void the adsorption of N-acylcarnosine to an unacceptable degree. It is therefore desirable that the anion exchange resin be used in a

  quantity which corresponds to twice or three times the equivalent of Nacylcar-

  nosine. The concentration of the aqueous solution which is passed through the column is not critical but is advantageously maintained at a level such that the concentration of ions of the mineral acid is between about 0.5 and 1 equivalent. per liter of solution. Space velocity

  is advantageously between about 0.5 and 2. -

  The aqueous solution is evaporated from the column under reduced pressure and evaporated to dryness to give the desired compound of

Formula 1).

  In both Method 1 and Method 2 above, when the molar ratio of N-acylcarnosine to aluminum alkoxide or aluminum mineral salt is varied, aluminum salt can be prepared.

  N-acylcarnosine which corresponds to the chosen molar ratio.

  The aluminum salts of N-acylcarnosine, which are representative and usable for the implementation of the invention, are hereinafter denoted by the letters A to 0 and are subjected to tests to determine their curative effect. on the ulcers of the digestive tract and also the degree of toxicity,

  the results being indicated in the experimental examples below.

  Samples:: r. ## STR2 ##

CH2CHCOO

  B COCH2CH2HC 3 AQ2 (OH) 5 (DL Form) C: (T C HOH A..3 (OH '(Fr / DA

L10N NHCOCH2CHNCOCH

  > NHCC2C2NCOCH 25At3 (OH) 4 (DL form)

CH2Cac0-

  ## STR3 ##

[N.N ECOCH2 CH2NHOH

I; CH2CHCOO

  (1 LNN6.N NHCOCH2CH2NHCOCH3 A3 (OH (Form L) I 1: ElCiCHlIOHC3 A. (OH) 2 (omeL

-CH2CHCOO

  G: NcN NHCOCH2CH2NHCOCH2CH3A (OH2 (Form L)) NHR = N NHCOCH2CH2NHCOCH2C3 OH (For L) C (2CHCO (L) 25 Ncc2.zC0CH2CR2] C3d sA3 (H1 8L - 1 CE 2CHCOOi == [- L: | HNNH2COCA0 ( ) - (Form L)

NROC2CH2ECC CJ

Cyn2H COO A (OH) 2 (Form L)

N NCOCH12CH2NHCO0

  : f1f CH2CHCOO CR = Au (OH) 2 (Form L)

N CHKCHCO0

  O :: m -CH2CHCOO A g2 (OH) 5 (Form L)

L: N N NHCOCH2CH2NHC 2H

  It will be noted that, as control compounds, the L-

  carnosine, L-glutamine, aluminum salt of N-acetyl-L-glutamine and aluminum-sucrose sulfate which are compounds known for their anti-ulcer action and which allow a comparison to be made. To determine

  the anti-ulcer action and the degree of toxicity of N-aluminum salts

  acylcarnosine according to the invention, rats and more particularly

  rats suffering from gastric ulcers of different types which

  allows to estimate the anti-ulcer action of the considered products.

  Experimental methods of determining the anti-aging effect

  ulcer and toxicity will be evident from reading the description

  Hereinafter: Shay Ulcer Experience: Groups of ten male Donryu rats each weighing 210 to 230 g were deprived of food for 48 hours. We

  ligated the pylorus of each rat according to the method of Shay et al (Gastrointestinal

  terology, 5, 43-61, 1945). For another 14 hours, we deprived the animals

  food and water, then sacrificed and stomachs removed.

  After collecting gastric juice, the ulcerated area (mm) in the anterior stomach of each rat was measured using a dissection microscope

  (x 10). The total area (mm) of all lesions in each rat is indicated

  as the ulcer index. Drug samples were administered

  immediately after ligation of the pylorus. The results

  experimental data are shown in Table 1.

TABLE 1

  Inhibition effects on Shay ulcer in experimental rats ...) Dose Index. Inhibition of ulceration, T & moin - 2.4 + 0., 7 to 1000 0.5 1 0; 79r2 B 1000 0-147 i 0 , 4 80.4 L-Carnosine 1000 2, .1 + 07 12.5 L-Glutamine 1000 2.2 + 0.8 8.3 Aluminum sulphate sucrose -1000 - 0.7. + 0. -8. -71 Witness - 2-, 9: i 9 O9

C, 000 0.7: .0) -8 7519

  D 1,000 0.80. 06 72r4 Aluminum salt of N-acetyl-L-glutamine 2,000 0,9 0t7 69zo Aluminum sulphate sucrose sucrose 1000. 08 + 0.6 -.72.4

,. , _ .., _

  - 2r5 * 0r7 E 100Q0 0M6 + 01.4 76f L-Carnosine 1 000 2 ', 2 +0; 7 810 N-acetyl-L-glutamic aluminum salt 2 000 0.7 +, 6 72.0 sodium sulphate aluminum sucrose.1000 0.8 ± 0.9 ..... 680 Control 2.9 ± 04 TF 1000 1.0 Or7 65.5 G i 000 019 + 09 69.0 H 1000 06 t0, 79.3 Aluminum salt of N-acetyl-L-glutamine 2000 o, 9 + 0.7 69.I0 Aluminum sulphate sucrose 1000 -08 -076 7214 l.0 _-. 08_ _ TABLE 1 (Continued) Experiment 2 Stress Ulcer: Groups of ten male Donryu rats each weighing 240 to 260 g were placed in a stress cage, the cage being used to immobilize the animals and then immersed in a water bath at 23 C at a level in accordance with the xipholde process described by K. Takagi et al (Jap J. Pharmac., 18 (9), 9-19, 1968) thus imposing a stress (or stress) on each rat. Seven hours after the immersion, each animal was removed from the water bath, immediately sacrificed with a blow to the head, and then the stomach of each rat was removed. The stomach was swollen slightly by injecting a 1% formalin solution and then dipped immediately into 1% formalin solution, after which it was incised along its largest curvature to measure the length (mm) of each lesion in the glandular part under a dissecting microscope (x 10). The total length (mm) of all lesions in each rat was indicated as the ulcer index. The drugs were administered by

  oral ten minutes before immersion in water.

  The results are shown in Table 2.

  Dose Index Samples Dose Index * Inhibition (mg / kg., P..O.) Of ulceration

Witness _ 3.1 1,1 -

I 1,000,017,015,7774

  J 1000 0r9 017 71.0 K 1 OQO 0.8 0.8 74t2 L i 000 0O9 + 1.0 71.0 M 1000 1t0 i 0.9 67.7

N 1000 11 0.8 64.5

  Aluminum salt of N-acetyl-L-glutamine 2,000 1,0 + 0r6 67t7 Aluminum sulphate 1,000 0,9 0,5 71g0 sucrose

TABLE 2

  Inhibitory effects on stress ulcer in rats

Dose Index -

  Samples (mg / kg, ulceration (%)% Inhibition

Witness - 15.2 3r2 -

A 300 8t0 2.8 47.4

1,000 4,4 2,2 71X1

B 300 8, I i 2.9 46t7

1,000 4,5 + 2,4 7014

L-Carnosine 300 14-, 2 i 37 6.6

1,000 10.7 7 2.2 29.6

  Aluminum sulphate sucrose i 000 675 + 6.0 56; 7

Witness - 17.5 315 -

E 300 9.2 3.0 47.4

  1,000 4,8 i-2,6 72t6 L-Carnosine 300 16,0 + 4-X0 8,6 1,000 12l1 i 2t5 30t9 N-acetyl-L-glutamine aluminum salt 2,000 5,5 4r8 68 6 Aluminum sulphate sucrose 1,000 7.3 6.8 58.3

7.3 _____ ___6_8____3

  A, B, E have the same meanings as above.

Example 3

  Ulcers caused by aspirin: we have no food -

  for 24 hours groups of ten male rats of the Donryu strain each weighing 220 to 230 grams. The pylar of each rat was ligated under anesthesia

  to the ether by the method of S. Okabe et al (JJ Pharmac., 24, 357-361, 1974).

  Following ligation of the pylorus, an aspirin (100 mg / kg) dose was administered orally to each rat. Seven hours after administration, animals were sacrificed under ether anesthesia and stomachs removed. After collecting the gastric juice and after treatment with a solution of formalin

  at 1%, the length of each lesion formed in the glandular portion was measured.

  lar. The total length (mm) of all lesions in each rat is indicated

  as the ulcer index. The orally administered

  drugs tested immediately after ligation of the pylorus.

  The results are shown in Table 3.

TABLE 3

  Inhibitory effects on ulcers rats caused by asDirine in

  A, B, and E have the same meanings as before.

  Experiment 4 Ulcers caused by indomethacin: Groups of 10 male Donryu rats each weighing 200 to 215 g were deprived of food for 24 hours. The pylori were ligated under anesthesia with ether and then indomethacin was administered subcutaneously at mg / kg to each rat. Seven hours after administration, the patients were sacrificed

  animals under ether anesthesia, the stomachs were removed and plunged

  10 minutes in a 1% formalin solution. The semi-fixed stomach was incised, following its greatest curvature, and the length (mm) of each lesion formed in the portion of the mucous membranes was measured using a dissection microscope (x 10). The total length (mm) of all samples Dose Index | (mg / kgOp) dewatering% Inhibition t

Witness - 17.7 + 23 -

A 1000 0T6 Or6 96.6

B 1,000 0.7 016 96.0

  L-Glutamine 1,000 610 + 2.2 66, r Aluminum sulphate sucrose 1,000 3.7 + 2.1 79.1

Witness - 17.5 + 3.5 -

  E 1000 0r6 + 0.6 96.4 L-Glutamine 1000 4.5 15 73.2 Aluminum sulphate sucrose 1000 2r0 11 88.1l The lesions of each rat are indicated as the ulcer index . We

  administered the drugs tested orally 10 minutes before

the pylorus.

  The results are shown in Table 4.

TABLE 4

  Inhibitory effects on indomethacin-induced ulcers in rats Samples Dose Index% Inhibition Samples (mg / kg, PO) of ulceration

Witness _ 163 + 2T4 -

A 300 675 272 60.1

  B 300 670 2.4 63r2 L-Carnosine 300 17.3 3t0 -0 L-Glutamine 300 9.5 + 4, 1 41.8 Aluminum sulphate sucrose 300 7.8 3.0 5271

-, .. i. l.

Witness _ 16.8 2-t1 -

  C 300 6T7 3r0O 60, 1 D 300 6,5 + 2t5 61,3 E 300 6r4 2r2 61,9 L-Carnosine 300 17,1 3,1-O -L-Glutamine 300 9-7,379 42t3 iSulphate aluminiu sucrose - 300 7.4 2.8 56r0 ______ ______ _____ ______ __7_4. 2r8___ __ __ 6,0 '__ __

  A, B, C, D and E have the same meanings as before.

Experience 5

  Ulcers caused by histamine: deprived of food

  48 hours of groups of 10 male Donryu rats each weighing 210 to 230 g and then administered i.p. histamine phosphate (300 mg / kg). Four hours after administration, the animals were sacrificed

  under anesthesia with ether and then the stomach was removed and immersed

  10 minutes in a 1% formalin solution. The semi-fixed stomach was incised along its largest curvature and the length (mm) of each lesion was measured under a dissecting microscope (x 10). The total length

  (mm) of all the lesions in each rat is referred to as the ulcer index.

  Orally tested drugs were administered prior to administration

histamine.

  The results are shown in Table 5.

TABLE 5

  Inhibitory Effects on Histamine-induced Ulcers in Rats Samples Dose (mg / kg, P..O.) Ulcer Index% Inhibition Control 241 47- A 300 976 18 60r2 B 300 9r4 20 61rO0 L-Carnosine 300 1773 3.2 28.2 Aluminum sulphate sucrose 300 14.4 At lt5 40r2 Witness

Witness _- 23T0 3.0 -

  E 300 9r1 1T9 60.4 L-Carnosine 300 18.0 + 2.7 21.7 Nacetyl-L-glutamine aluminum salt 2000 8.5 3.0 63T0 Aluminum sulphate sucrose 300 10r7 + 2r1 53 5

  A, B, and E have the same meanings as before.

  Experiment 6 Acute toxicity: Male rats were divided into two groups and

  females of the Wister strain each weighing 150 to 200 g, each group comprising

  10 rats and the oral aluminum salts were

  N-acylcarnosine according to the invention. The treated rats were subjected to an observation

  for seven days after administration.

  The results are shown in Table 6.

TABLE 6

LD50 values in rats

  A, B, C, D and E have the same meaning as before.

  As is evident from the examination of the experimental results

  Table 1 to 6. The aluminum salts of Nacylcarnosine according to the invention show an excellent inhibitory action on ulcers of various types. Specifically, when aluminum salts of N-acylcarnosine are administered in a dose of 300 to 1000 mg / kg to rats for Shay ulcer, stress ulcer, aspirin-induced ulcer, indomethacin-induced ulcer and histamine-induced ulcer, effective inhibition of each of the ulcers is found, and these compounds are therefore better than

  all known agents for the fight against ulcers.

  In the acute toxicity test, even when the aluminum salts of N-acylcarnosine are administered orally at a dose as high as g / kg, no rat death and little or no change in

general symptoms.

  Accordingly, the aluminum salts of N-acylcar-

  nosine according to the invention as a medicament against ulcers of the digestive tract.

  with greater efficacy and safety than L-glutamine, aluminum salt of N-acetyl-L-glutamine and aluminum sulphate sulfate, LD 50 (mg / kg, PO) Samples - male 1 female

A> 10,000> 10,000

B> 10,000> 10,000

C> 10,000> 10,000

D> 10,000> 10,000 -

E -> 10,000> 10,000-.

  I3 which are the most commonly used anti-ulcer agents. The salts according to the invention may be administered orally or parenterally and may be used in the form of tablets, capsules, powders, granules and the like.

  syrups for the oral route and also in injectable form by way of

  térale. The dose administered is in general between 500 and 5000 mg per day for adults, the dose being variable according to the age of the patient and

according to the symptoms of the disease.

  The following examples serve to illustrate the invention without any

limit its scope.

Example 1

  a) A solution of 5.36 g of N-acetyl-DL-carnosine is heated

  (A. Lukton and A. SISTI, J.O.C. 26, 617, (1961) in 100 ml of water at a temperature of

  about 40C. To this solution is added dropwise with vigorous stirring 90 ml of a solution of isopropyl alcohol containing 4.08 g of aluminum isopropoxide. After the addition, the reaction mixture was stirred at 40 ° C. for ten minutes and insoluble substances were removed by filtration. The solvent is removed under reduced pressure and the oily residue is added isopropyl alcohol for its solidification. The resulting solid is ground and powdered. The powder is washed with isopropyl alcohol suitably and dried at 60 ° C under reduced pressure to obtain 6.5 g (quantitative yield) of a colorless powder (mp 2100 ° C (dec)). . 5 g of the powder thus obtained are dissolved in 30 ml of water. 4.8 g of an aluminum salt of N-acetyl-DL-carnosine are obtained.

  from this solution by spray drying at 80 ° C.

  mp: 215 ° C (decomp.) IRν KBr cm-1: 3400 (OH), 1630 (C = O), 1450, 1380 (1H NMR (D20) δ): 1.88 (3H, s, -COCH3) 2, r43 (2H, m, -CH2CH2NHCOCH3) 3.28 (4H, m, -COCH2CH2N ', -CH2CHCOO) I 4.09 (1H, m, -CH2CHCOO) 7t05, 8.10 (1Hx2, sx2, protons of the imidazole nucleus) Elemental analysis for? (C11H15N4O4)? (OH) 2: Calculated: C 40 R25, H 5.22, N 17.07, -AL 8f22 (%) Found: C 40.10, H 5 R 41, N 16 R 77, A u 8.01 (%) These analytical data confirm the following structure (A)

CH2CHCOO

  A: NHCOCH2C2NHCOCHA (OH) 2 (DL form)

NCCH2CHCO 23

  b) A solution of 4.5 g of N-acetyl-DL-carnosine in 30 ml of water is heated to a temperature of approximately 60 ° C. and then

  25 ml of an isopropyl alcohol solution are added with vigorous stirring.

  3.75 g of aluminum isopropoxide. After the addition, stir

  the reaction mixture at 60 ° C. for 4 hours, the isopropyl alcohol is removed.

  under reduced pressure of the reaction mixture and filtered off.

  all insoluble substances in the residual aqueous solution. We

  5.1 g (quantitative yield) of an aluminum salt of N-acetyl-DL-

  carnosine as a colorless powder from the filtrate by drying

by spraying at 80 C.

  The analytical data are strictly the same as those obtained in paragraph a) above.

Example 2 -

  a) A solution of 600 g of N-acetyl-L-

  carnosine dissolved in 5.2 liters of water. 3.8 liters of a solution of isopropyl alcohol containing 500 g of aluminum isopropoxide are added dropwise with vigorous stirring to this solution. After this addition,

  the mixture is stirred for 3 hours at 60 ° C., after which the isopropyl alcohol is removed.

  under reduced pressure and the insoluble substances are removed by filtration of the reaction mixture. 690 g of an aluminum salt of N-acetyl-L-carnosine are obtained in the form of a colorless powder from the filtrate.

  spray drying at 80 C.

  m.p. 235 C (decomp.) [Α] 20 + 15.90 (C = 5% in H 2 O) KBr cm-1: 3400 (OH), 1360 (CO), 1450, 1380 NMR (D 2 O) δ: 1.98 ( 3H, s, -OCOC3) 2 R53 (2H, m, -CH2CH2NHCOCH3) 3.40 (4H, m, -COCH2CH2N- •, -CH2CHCOO) 4t20 (1H, m, CH2CHCOO) 7.25, 8.53 (1H2) , sx2, protons of the imidazole nucleus) Elemental analysis for (CllH15N464) Az (OOi) 2: 30. Calculated C 40t25, H 5 R 22, N 17, 07, Al 8 R 22 (%) Found: C 40.13, H 5.19 , N 17.01, Ak 8.27 (%)

  These analytical data confirm the following structure (E).

  ## STR3 ## wherein R 2 is CH 2 CHCOO 2 H (NHCOCHO 3) 2 (Form L)

  b) A solution of 120 g of N-acetyl-L

  carnosine dissolved in one liter of water. To this solution add drop to

  800 ml of an isopropyl alcohol solution with vigorous stirring.

  containing 100 g of aluminum isopropoxide. After the addition, the mixture is stirred for three hours at 60 ° C. and is then removed under reduced pressure.

  isopropyl alcohol and finally the insoluble substances are removed by filtration.

  treatment of the residual aqueous solution and the filtrate is concentrated to 300 ml.

  The resulting solution is freeze-dried and 151 g of aluminum salt are obtained.

  N-acgtyl-L-carnosine as a colorless powder.

  The analytical data are exactly the same as those

obtained in paragraph (a).

  c) A solution of 3 g of N-acetyl-L-

  carnosine dissolved in 25 ml of water and added dropwise to this

  solution, with vigorous stirring, 20 ml of a solution of isopropyl alcohol

  than containing 2.5 g of aluminum isopropoxide. After the addition, the mixture is stirred for 3 hours at 60 ° C. The insoluble substances are removed from the residual aqueous solution by filtration and the filtrate is concentrated to dryness in order to obtain 3.5 g of an aluminum salt. Nacetyl-L-carnosine under

form of a colorless powder.

  The analytical data are exactly the same as those

obtained in paragraph (a).

Example 3

  0.816 g of aluminum bisisopropylate is heated in 6.6 ml of isopropanol.

  panol and then stirred at about 60 ° C for 30 minutes, then 0.536 g of N-acetyl-DL-carnosine. The resulting mixture is stirred at 60 ° C. for 3 hours, then the isopropyl alcohol is removed under reduced pressure.

10 ml of water are added to the residue and the mixture is stirred at 60 ° C. for one hour.

  The insoluble substances are removed by filtration and the filtrate is condensed.

  Isopropyl alcohol is added to the residue. The resultant solidified aluminum salt is collected by filtration. After sufficient washing of the solid product with isopropyl alcohol, 0.81 g (quantitative yield) of

  aluminum salt of N-acetyl carnosine in the form of a colorless powder.

  m.p. 280 C <(decomp.) IRv KBr cm-1: 3500 - 3200 (O5I) max

1660 - 1610 (C = O)

1590 1540 (COO)

  NMR (D20) 6: 2 R00 (3H, s, -COCH3) 2.54 (2H, m, -CH2CH2NH-) 3-44 (4H, m, COCH2CH2N1, -CH2CH ') 4t68 (1H, m, -CH2CHCOO) 7.36, 8.66 (1Hx2, sx2, protons of the imidazole nucleus) Elemental analysis for (Cl1H20N4O9) A 2 (OH) δ: Calc .: C 32.52, H 4.96, N 13.79, AZ 1328 (%) Found: C 32.63, H 5.27, N 13.89, AP 13.31 (%)

  These analytical data confirm the following structure (B).

C 2CECOO

B: 1NC2C2C C3 AZ2 (OH) (DL Form)

Example 4

  a) is heated to about 60 C a solution of 60 g of N-acetyl-DL-

  carnosine in 500 ml of water and 250 ml of an isopropyl alcohol solution are added dropwise with vigorous stirring to this solution.

  containing 27.5 g of aluminum isopropoxide.

  After the addition, the reaction mixture is stirred at 60 ° C. for 3 hours, the insoluble matter is removed by filtration, the solvent is concentrated to 1 / 10th of its volume under reduced pressure and to the viscous solution thus obtained. isopropyl alcohol to allow

  solidification. The resulting solid is ground and powdered.

  Then, the powder is sufficiently washed with isopropyl alcohol and dried at 60 ° C. under reduced pressure to obtain 61.8 g (quantitative yield) of an aluminum salt of N-acetyl-DL-carnosine. b) 5 g of the thus-obtained powder of aluminum salt of N-acetyl-DL-carnosine are dissolved in 30 ml of water and 4.8 g of the aluminum salt are obtained;

  N-acetyl-DL-carnosine from this solution by drying it by spraying.

at 80 C.

  mp: 223 C (decomp.) NMR (D 2 O): 1.91 (3H, s, COCH 3) 2 R 43 (2H, t, COCH 2 (? 2NH) 3 R 10 (2H, m, -CH 2 CHCOO) 3 R 28 (2H, t, -COCH2CH2NH-) 4t44 (1H, m, CH2CHCOO) 7.07, 8T25 (1Hx2, sx2, protons of the imidazole nucleus) These analytical data confirm the following structure (C)

C H2CCOO "

  C: NNHCOCH 2 CH 2 NHCO 3 H 5 AZ 3 (OH) 4 (DL Form) c) 1.39 g of aluminum isopropoxide in 20 ml are heated to 60 ° C.

  of isopropyl alcohol and 3.04 g of N-acetyl-DL-carnosine are added at 60 ° C.

  The mixture is stirred for 1 hour and then 10 ml of water are added.

  After stirring for 30 minutes, the insoluble substances are removed by filtration of the resulting homogeneous solution. The isopropyl alcohol is removed by evaporation under reduced pressure from the filtrate. The residual aqueous solution is lyophilized and 3.35 g (quantitative yield) of

  aluminum salt of N-acetyl-DL-carnosine as a colorless powder.

  The analytical data are exactly the same as those

  obtained in paragraph b) above.

Example 5

  To a solution of 1.33 g of aluminum isopropoxide in 20 ml of isopropyl alcohol is added 2.91 g of N-acetyl-L-carnosine at 60 ° C. and stirred for one hour. 10 ml of water are added and the mixture is stirred for 30 minutes until homogeneous. After filtration, isopropyl alcohol is removed from the filtrate by evaporation under reduced pressure and

  lyophilizes the residual aqueous solution to obtain 3.2 g (quantitative yield).

  tative) of an aluminum salt of N-acetyl-L-carnosine as a colorless powder. P-f: 218 C (decomp.)] +19.0 (C = 5% in H 2 O)

D 2

IRV KBr cm1 3400 (OH) max

1600 (CO)

  NMR (OD): 1.91 (3H, s, -COCH3) 2.43 (2H, t, -COCH2CH2NH-) 3.10 (2H, m, CH2CHCOO) 3 R28 (2H, t, -COCH2CHNH-) 4744 ( 1H, m, -CH 2 CHCOO) 7.07, 8.25 (1H x 2, SX 2, protons of the imidazole nucleus) Elemental analysis for (ClHH 1 SN 4 O 4) 5A 3 (OH) 4: Calculated: C 44 R 47, H 5.37, N 18.86 (%) Found: C 44, 39, H 5r34, N 18.62 (%) These analytical data confirm the following structure (D)

H N NHOCH 2CHCO O-)

  D: CH2C HHCOCOCH A3OH) 4 (Form L) kNI N NHCOCHvu2CH2NHCC3

Example 6

  To a solution of 0.70 g of aluminum isopropoxide in 20 ml of isopropyl alcohol is added 2.76 g of N-acetyl-L-carnosine at 60 ° C. and the mixture is stirred for 1 hour. 10 ml of water are added to the mixture which is stirred for 30 minutes until homogeneous. After filtration, isopropyl alcohol is removed by evaporation under reduced pressure and the residual aqueous solution is lyophilized to obtain 2.8 g (quantitative yield) of

  aluminum salt of N-acetyl-L-carnosine as a colorless powder.

  P-f-: 220 C (decomp.) [1] + 22.8 (C = 5% in R2O) XKBr-1 IRvBax cm 1 NMR (OD) ax

NMR (D20O) 6:

3400 (OH), 1630 (C = O), 1390, 1300

  1.63 (3H, s, -COCH3) 2.21 (2H, t, -C-CHCH2NH-) I 2r96 (2H, m, -C2CHCOO)

3.16 (-COCH2CH2NH-)

  44 (1H, m, -CH3CHCOO) 7.41, 8.81 (1Hx2, sx2, protons of the imidazole nucleus) Elemental Analysis for (Cl11H15N4O4) 3A2 .: Calc .: Found:

C 47.82, H 5.48, N 20.28 (%)

C 47.58, H 5.24, N 20.08 (%)

  These analytical data confirm the following structure (F)

(/ - CH2CHCOO

F: HCOCHCHNHCOCHj A2 (Form L)

Example 7

  To a solution of 1.04 g of aluminum isopropoxide in 20 ml of isopropyl alcohol is added 2.73 g of N-acetyl-L-carnosine at 60 ° C.

  2.9 g (quantitative yield) of an aluminum salt of N-acetyl-L-

  Carnosine in the form of a colorless powder by the same technique as in

example 6.

  mp: 218 ° C (decomp.) [] 25: +19.6 (C = 5% in H 2 O) KBr m 1: 3400 (OH), 1630 (C = O), 1390, 1300 max I (D o) 6: 191 (3H, s, -COCH 3)

2

  2-, 42 (2H, t, -COCH2CH2N-) 3.10 (2H, m, -CH2CHCOO) 3.32 (2H, t, COCH2CH2NH-) 4.44 (1H, m, -CH2CHCOO) 7 , 09, 8t32 (1Hx2, sx2, protons of the imida nucleus: Elemental analysis for (CllH15N4O4) 2AuOH: Calc .: C 45.67, H 5y41, N 19r37 (%) Found: C 45r84, H 5112, N 19r45 - (% )

  These analytical data confirm the following structure (G).

  F: CH 2 HHACOOrme L) G: H N NHCOCH 2 CH 2 NHCOCH 3) 2 AOH (Form L)

Example 8

  To a solution of 3.13 g of aluminum isopropoxide in 35 ml of isopropyl alcohol is added 1.37 g of N-acetyl-L-carnosine at 60 ° C. and the mixture is stirred for 1 hour until homogeneous. then 25 ml of water are added to the reaction mixture and stirred for 30 minutes. The isopropyl alcohol is evaporated under reduced pressure and water is added to the residual solution. The clear solution is lyophilized and 2.4 g (quantitative yield) of an aluminum salt of N-acetyl-L-carnosine under

form of a colorless powder.

  mp: 280 ° C (decomp.) [α] 25: +8 (C = 1% in H 2 O) <Br -r IRV KBax cm 3400 (OH) 1640 (0 = 0), 1400 NMR (D9O) ): 1779 (3H, s, -COCH3) 2 R32 (2H, t, -COCH2CH2NH-) 3.21 (2H, -m, -CH2CHCOO) 3.69 (2H, t, -COCH2CH2NH-) 4; 1H, m, -CH 2 CHCOO) 7.04, 8.17 (1H x 2, sx 2, protons of the imidazole nucleus) Elemental analysis for (Cl 1 H 15 N 4 O 4) Al 3 (OH) 8: Calculations: C 27 F 28, H 4.80, N 11.57 (% Found: C 27 R 34, H 4.62, N 11t 65 (%)

  These analytical data confirm the following structure (H).

CH CHO

  2i Au (Form L 31: NHCOCH2CH2NHCOCH3 A3 (OH) 8 (Form L)

Example 9

  a) N-propionyl-L-carnosine: To a solution of 2.42 g of L-carnosine dissolved in 13 ml of water, 6.5 ml of acetone are added. Then add

  dropwise and simultaneously with this solution, 4.14 g of chloride of

  pionyl and 7.6 g of triethylamine at a rate such that the reaction mixture does not exceed a temperature of 20 C and its pH is maintained between 7.0 and 7.5. This dropwise addition requires about 1 hour. After the addition, the acetone is evaporated under reduced pressure and the residue is adsorbed on a strongly anionic exchange resin (SA-10A) in an amount of 130 ml. The anionic resin is washed with water and eluted with normal acetic acid, and the eluent is then adsorbed on a strongly cationic exchange resin (SK-IB) in an amount of 10 ml. After washing with water the cationic resin and eluting with 2% ammonia, the eluent is evaporated under reduced pressure to remove most of the ammonia. The residue is passed through 30 ml of a weak cationic exchange resin (IRC50) and the residue portion which has not been adsorbed is distilled to dryness under reduced pressure to thereby obtain a crude product. Recrystallization

  of this crude product in a methanol / acetone mixture (2/3) gives 1.46 g of N-

  propionyl L-carnosine as colorless crystals (48% yield).

  Pf-: 206-209 ° C (dec.) [] +20.40 (C = 3% in H2O) KBr -1 IRv KBx cm: 3300 (OH), 1630 (CO), 1540, 1390 max NMR (D 20 ): 1.06 (3H, t, J-8Hz, CH2CH3) 2.18 (2H, q, J = 8Hz, -CH2CH3) 2r44 (2H, t, J = 7Hz, -NHCOCH2CH2NH-) 3.14 (2H) , m, -CH2CHCOO) 3 R36 (2H, t, J = 7, -NHCOCH2CH2NH ') 4.44 (1H, m, CH2CHCOO) 708, 8.48 (1Hx2, sx2, protons of the imidazole nucleus) Elemental analysis for C12H18N4O4: Calculated: C 51.04, H 6.44, N 19785 (%) Found: C 5095, H 643, N 19.77 () Found: C 50195, H 6t43, N 19.77 - (% b) A a solution of 0.8 g of aluminum isopropoxide in 15 ml of isopropyl alcohol is added 1.11 g of N-propionyl-L-carnosine at 60 ° C.

  1.3 g (quantitative yield) of an aluminum salt of N-propionyl

  Carnosine by the same technique as in Example 6.

  mp: 228 ° C (decomp.) [+1774 (C = 3% in H 2 O) KBr 1 IR 4KBr cm-1 3400 (OH), 1640 (C = O), 1540, 1400 max NMR tD 2 0) 6: 1 R 02 ( 3H, t, -COCH 2 CH 3) 2, 11 (2H, q, -COC 2 CH 3) 2140 (2H, t, -COCH 2 CH 2 NH-) 3708 (2H, m, -C 2 CHCOO)

R28 (2H, t, -COCH2CH2NH-).

  417 (1H, m, -CH2CHCOO) 7-07, 8.26 (E1Hx2, sx2, protons im-idazol-e) Elemental analysis for (C12H17N4O4) AZ (OH) 2: Calculated: C 42, r10, H 5761, N 16.37 Found: C 41.88, H 5.83, N 16.12

  These analytical data confirm the following structure (I).

  fCH2CHCOO I: AHCO CH2CH2NHCCH2H3 A (OH) 2 (Form L) L U V CCgCiNCCH 2C Ij

Example 10

  To a solution of 0.72 g of aluminum isopropoxide in 15 ml

  of isopropyl alcohol, 1.97 g of N-propionyl-L-carnosine is added at 60 ° C.

  2.1 g (quantitative yield) of a Npropionyl aluminum salt are obtained.

  L-carnosine in the form of a colorless powder in the same way as in

example 6.

  of the core (%) (%) m.p .: 220 C (decomp.)

25

  [?] +14750 (C = 1% in H2O) KBr -1 IR VMaKBx cm 3400 (OH), 1640 (C = O), 1540 NMR (D20) 1: 1.02 (3H, t, -CH2CH3) 2 , 2710 (2H, q, -CH2CH3) 2, -42 (2H, t, -COCH2CH2NH-) 3r15 (2H, m, -CH2CHCOO) 3 R35 (2H, t, -COCH2CH2NH-) 4.44 (1H, m, -CH 2 CHCOO) 7.80, 8.27 (1H x 2, sx 2, protons of the imidazole nucleus) Elemental analysis for (C 12 H 17 N 4 O 4) 2AZOH: Calculated: C 47.51 H 5.83, N 18.48 (%) Found: C 47t37, H - 5.78, N 18.37 (%) These analytical data confirm the following structure (J)

CH2CHCOQO

  HN N NHCOCH2CHNHCOCH2CH3 A2OH (Form L)

Example 11

  To a solution of 0.76 g of aluminum isopropoxide in 15 ml

  of isopropyl alcohol, 1.75 g of N-propionyl-L-carnosine are added at 60 ° C.

  1.9 g (quantitative yield) of a Npropionyl aluminum salt are obtained.

  L-carnosine in the form of a colorless powder in the same manner as in Example 6. m.p .: 220 C (decomp.) [A] 25: (C = 1% in H 2 O) IR KBr c-1: max

NMR (D20) 6:

(OH), 1640 (C = O), 1540, 1400

  1.02 (3H, t, -CH2CH3) 2.10 (2H, g, -CHCH3) 2.42 (2H, t, -COCH2CH2NH-) 3, 13 (2H, m, -CH2CHCOO) 3.32 (2H; t, -COCH2CH2NH) 444 (1H, m, -CH2CHCOO) 7, 08, 8.27 (1Hx2, sx2, protons of the imidazole nucleus) Elemental analysis for (C12H17N4O4) 5AM3 (OH) 4: Calculated: C, 46.32 , H 5.78, N 18 R01 (%) Found: - C 46725, H 5.72, N 17.94 (%) These analytical data confirm the following structure (K) CH2CHC00 K: HCOCH2CH2NHCOCH2CH3I 5AA3 (OH) 4 (Form L)

K: I "NHCOCH2CH2NHCOCH2CH3

Example 12

  a) N-heptanoyl-L-carnosine: To a solution of 2.42 g of L-carnotine

  sine in 13 ml of water, 6.5 ml of acetone are added. 6.36 g of heptanoyl chloride is then added to this solution and the reaction mixture is treated as described in paragraph a) of Example 9 to obtain a crude product. Recrystallization of the crude product from water: acetone (1: 2) gives 1.66 g of N-heptanoyl-L-carnosine in the form of colorless crystals.

(46% yield).

  p. f .: 214 - 217 c (decomp.) [25 + 4r7 (C = 2% in H2O)

[D 2

  IRvmKBr cm -1: 3290, 1635, 1530, 1400 nmr (D 2 O) δ: 0.72 (3H, m, -CH 3) OR 86 '156 (8H, m, -CH 2 x 4) 2 R 06 (2H, t, J = 7 Hz, -COCH2CH2-) 2T35 (2H, t, J = 7Hz, -NHCOCH2CH2NH) 2? 94-3.14 (2H, m, -CH2CHCOO) 3T26 (2H, t, J = 7Hz, NHCOCH2C2NH) 4H264t44 (1H, m , -CH2CHCOO) 7710, 8.42 (1Hx2, sx2, protons of the imidazole nucleus) Elemental Analysis for C16H26N4O4: Calculated C 56.77, H7r76, N 16.56 (%) Found: C 56t81, H 7.85, N 16.38 (%) b) To a solution of 0.68 g aluminum isopropoxide in 15 ml

  of isopropyl alcohol, 1.13 g of N-heptanoyl-L-carnosine at 60 ° C. is added.

  1.3 g (quantitative yield) of an aluminum salt of Nheptanoyl are obtained.

  L-carnosine in the form of a colorless powder in the same way as in

example 6.

  mp: 281 t D25 KEr IR VaBr m = +0 4a -7 -1 cm (decomp.) (C = 1% in H 2 O) 3400 (OH 2 O, 2930, 2860 (alkyb), 1640 .- (C-OO) , IR (D20δ: 0.80 (3H, t, CH2CH3) 1.20 (8H, m, -CH2-x4) 2,12 (2H, t, -CH2C2CO-) 2T40 (2H, t, COCH2CH2NH- 3.07 (2H, m, -CH2CHCOO) 3.31 (2H, t, -COCH2CH2NH-) 4t44 (1H, m, -CH2CHCOO) 7rO6, 8728 (1Hx2, sx2, protons of the imidazole nucleus)

  Elemental analysis for (C16H25N4O4) AZ (OH) 2:

  Calculated: C 48723, H 6.84, N 14.06 (%) Found: C 48.03, H 6r87, N 13t77 (%) These analytical data confirm the following structure (L) NHCOCH2COO H2NHCOCH3j A (OH) 2 ( Form L)

RN N NHCOCH2CH2NCOC6H3

Example 13

  a) N-benzoyl-L-carnosine: To a solution of 2.42 g of L-carnosine dissolved in 13 ml of water, 6.5 ml of acetone are added. 6.32 g of benzoyl chloride are then added and the reaction mixture is treated in the same way.

  than in paragraph a) of Example 9 to obtain a crude product. The recrystall

  The crude product in a mixture of methanol and acetone gives 1.69 g.

  N-benzoyl-L-carnosine as colorless crystals (48% yield).

  Mp: 217-219 ° C (decomp.) [Α] D: +10.3 (C1-1% in H20) KBr -1 IR vax cm at 3280, 1640, 1520, 1385 NMR (D20): 2, 48 (2H, t, J = 7Hz, -COCH2CH2NH-) 3rO2 (2H, m, -CH2 COO2) 3T46 (2H, t, J = 7Hz, -COCH2C- 2NH-) t 4737 (1H, m, CH2CHCOO) 6.99 [1H, s, Droton- imidazole nucleus (position 7.1 - 7.6 (5H, m, protons of the benzene nucleus) 814 [1H, s, proton of the imidazole nucleus (position Elemental analysis for C16H18N4O4: Calcd: C 58.16, H 5.50, N 16.96 (%) Found: C 58.21, H 5.65, N 16t93 (%) b) To a solution of 0.8 g of aluminum isopropoxide in 15 ml of isopropyl alcohol, 1.27 g of N-benzoyl-L-carnosine are added at 60 ° C.

  1.5 g (quantitative yield) of an aluminum salt of N-benzoyl-L-

  carnosine in the form of a colorless powder in the same manner as in example 6. mp: 280 C <(decomp.) la] D5: + 6r2 (C = 1% in H2O) KBr IR iax cm: 3400 (OH ), 1630 (C = O), 1540, 1400 -Max NMR (D20O) δ: 2r55 (2H, t, -COC2CH2NH-)

2 1

I

3707 (2H ,, -CH2CHCOO)

  3.55 (2H, t, -COCH2CH2NH-) 4T44 (1H, m, -CH2CHCOO) 6.99 [1H, s, imidazole ring proton (position 5)] 7744 (SH, m, benzene ring protons) 8r08 [1H, s, proton of the imidazole nucleus (position) Elemental analysis for (C 6 H 17 N 4 O 4) Au (OH) 2: Calculated C 49.23, H 4.92, N 14 36 (%) Found: C, 49.18, H 4 , 86, N 14418 (%) These analytical data confirm the following structure (M)

- -

  M: f CH2CHCOo 0 0 AQ (OH) 2 (Form L) t HE C NHCOCH2CH2NHCO

Example 14

  To a solution of 0.80 g of aluminum isopropoxide in 15 ml

  of isopropyl alcohol, 0.64 g of N-benzoyl-L-carnosine at 60 ° C. is added.

  0.9 g (quantitative yield) of a Nbenzoyl aluminum salt are obtained.

  L-carnosine in the form of a colorless powder in the same way as in

example 6.

  Mp: 2.35 C (decomp.) * [D] 25: + 4T1 (C = 1% in H2O) IR VD2 cm ':

R (D20) 6

  Elemental Analysis Calculated: Found:

3400 (OH), 1630 (C = O), 1540

  2? 55 (2H, t, -COCH2CH2NH-) 3,10 (2H, m, -C- CHCCO) 3r56 (2H, t, COCH2CH2NH-) 4.44 (1H, m, -CH2CHCOO) 6-99 [1H, s, proton of the imidazole ring (position 5)] 7.45 (5H, m, protons of the benzene ring) 8708 [1H, s, proton of the imidazole ring (position 2)] Read for (C16H17N404) A2 (OH) 5

C 41.03, H 4.74, N 11.96 (%)

C40.88, -H 4.67, N 11.89 (%)

  These analytical data confirm the following structure (O).

  o: L or CH 2 C co O-: Ao 2 -CzHO 2 '(OH) 5 R 2 -N EnCOCE 2 ClNHC (Form L;

Example 15

  a) N- (o-methoxy) benzoyl-L-carnosine: To a solution of 2.42 g of L-carnosine dissolved in 13 ml of water, 6.5 ml of acetone are added. 7.67 g of o-methoxybenzoyl chloride are then added and the reaction mixture is treated in the same manner as in paragraph a) of Example 9 to obtain a crude product. This crude, highly hygroscopic product is then washed with ether to give 1.54 g of N- (o-methoxy) benzoyl-L-carnosine in the form of

  colorless crystals (yield: 40%).

  mp: 203 C (decomp.) [C] 25 +7 6 (C = -1% in H 2 O) IR v KBr cm 1 max

NMR (CD30D) 6 :.

3380, 1630.

  R15 (2H, t, J = 7Hz, -COCH2CH2NH-) 3716 (2H, m, -CCHCOO)! 3716 C2H, m, Cl2CHCOO) 3.60 (2H, t, J = 7Hz, -COCH2CH2NH-) 3t86 (3H, s, -OCH3) 4.55 (1H, m, -CH2CHCOO) 6785-7r85 (5H, m.p. protons of the benzene and proton nucleus of the imidazole nucleus) 8r33 (1H, s, proton of the imidazole nucleus) Elemental analysis for C17H20N4O5: Calculated: Found:

C 56.65, H 5.60, N 15? 55 (%)

C 56.61, H 5758, N 15.61 (%)

  b) To a solution of 0.68 g of aluminum isopropoxide in 15 ml of isopropyl alcohol is added 1.20 g of N- (o-methoxy) benzoyl-L-carnosine

  at 60 ° C. 1.40 g (quantitative yield) of an aluminum salt of N-

  (o-methoxy) benzoyl-L-carnosine in the form of a colorless powder of the same

way than in example 6.

  p. ú: 280 C <(decomp.) [a] 2D5: +2.7 (C = 1% in H2O) IRv KB cm-: 3400 (OH), 1630 (C = O), 1540, 1400, 1310 Max NMR ( D20) 6: 2r56 (2H, t, -COCHCH2NH-) I. 3.29 (2H, m, -C2CHCOO) 3.55 (2H, t, -COCH2CNH-) 3t83 (3H, s, -OC3) 4 , 44 (1H, m, -CH2CHCOO) 6r95-7-65 (SH, m, Protons of the benzene ring and proton of the imidazole ring) 7.96 (1H, s, proton of the imidazole ring) Elemental analysis for (C17H19N405) AQ (OR) 2: Calculated: C 48.57, H 5.05, N 13, t33 (%) Found: C 48.42, H 4f92, N 13.18 (%)

  These analytical data confirm the following structure (N).

  N: m ^ CH2CECOO CH30A A OH) (Form L) RN EwN NHCOCH2CH2NHCO_ AJ

Example 16

  Preparation: I g of a drug against the ulcer of the digestive tract pre-

  prepared as granules and containing the following ingredients: Ingredients Compound E * Milk Sugar Corn Starch Quantities / mg mg 400 mg 400 mg TOTAL: 1,000 mg

  * The compound E is the same as defined above.

Claims (17)

  1. Aluminum salt of an N-acylcarnosine, characterized in that it corresponds to the formula (I) CH2CHCOO Am () NHCOCH2CH2NHCOR (   in which R represents a lower alkyl radical of 1 to 6 carbon atoms, a phenyl radical or a phenyl radical substituted by a lower alkoxy group ,. is an integer from I to 5, m is an integer   from I to 3 and n represents 0 or an integer from 1 to 8.   2. Salt according to claim 1, characterized in that = 1, m = 1 and n = 2.   3. Salt according to claim 1, characterized in that = 1, m 2 and n- = 5.   4. Salt according to claim 1, characterized in that Q = 1, m 3 and n = 8.   5. Salt according to claim 1, characterized in that = 2, m = and n = 1.   Salt according to claim 1, characterized in that Q = 3, m 1 and n = zero.   Salt according to claim 1, characterized in that Q = 5, m = 3 and n = 4.   8. Salt according to claim 1, characterized in that R represents   is an alkyl radical of 1 to 6 carbon atoms.   Salt according to claim 1, characterized in that R represents the methyl radical.   10. Salt according to claim 1, characterized in that the acyl-   Carnosine is in the form L. It. Process for the preparation of an aluminum salt of N-acylcarnosine   of formula (I) as defined in any one of claims I   at 10, characterized in that it consists in reacting an N-acylcarnosine of formula (II) my CH2CHCOOH UIN N NHCOCIH2CH2NHCOR   wherein R is as defined above, with an aluminum alkoxide in the presence of a solvent, and then removing from the reaction medium, the solvent   and the alcohols formed as side products.   12. Process according to Claim 11, characterized in that the aluminum alkoxide is chosen from methylate, ethylate, isopropanol and   pylate, t-butylate and aluminum cyclohexylate.   13. The method of claim 11 or 12, characterized in that the solvent is selected from water, methanol, ethanol, isopropanol,   butanol and mixtures thereof.   14. Process according to claim 11, 12 or 13, characterized in that the reaction is carried out at a temperature comprised between ambient and 80 C.   15. Process for the preparation of an aluminum salt of N-acylcarnosine   of formula (I) as defined in any one of claims 1 to   10, characterized in that it consists in reacting a acylcarnosine of   mule (II) as defined in claim 11, with a mineral salt   of aluminum, and then to separate, using a resin-exchange the product re- looked for the reaction mixture.   16. Process according to claim 15, characterized in that the inorganic aluminum salt is chosen from the aluminum salts of the acid   sulfuric acid, nitric acid and hydrochloric acid.   Method according to claim 15 or 16, characterized in that   said exchange resin is a weakly basic anionic exchange resin   than. 18. The method of claim 15 or 17, characterized in that   the exchange resin is used in a double or triple proportion of the equivalent of acylcarnosine.   19. A medicament for inhibiting ulcers of the digestive tract, characterized in that it comprises an effective dose of an aluminum salt of   N-acylcarnosine as defined in any one of claims 1 to 10.