PL210209B1 - New application of undecane-2-ol - Google Patents

Description

The present invention relates to a new use of undecan-2-ol.

In recent years, there has been an intensification of research on the biological activity of compounds of natural origin. So far, the biological properties of essential oils have been best understood. Essential oil is a mixture of sometimes several dozen chemical compounds and the synergistic effect of individual components is responsible for its biological properties. Obtaining essential oils requires a large amount of natural resources, is quite expensive, and therefore the price of the oils is high. Moreover, the chemical composition of oils depends to a large extent on the climatic conditions from which the raw materials for their production come from and is often variable. Therefore, research has been undertaken to determine which of the oil components are mainly responsible for their biological properties, whether they can be obtained by chemical synthesis and whether those obtained by chemical synthesis are identical to the natural ones.

Interesting in this respect turned out to be the aliphatic component of essential oils - undecan-2-ol. Undecan-2-ol can be obtained by simple, ecological and efficient chemical synthesis and the synthesis product has a status identical to the natural one. Undecan-2-ol is characterized by a fruity-fat odor and has so far been used as an ingredient in food flavors and flavor bases.

The new use according to the invention is that undecan-2-ol is used as an immunostimulating agent, stimulating cellular and humoral defense mechanisms, antibody production and the production of angiogenic cytokines, especially as an agent that inhibits the growth and angiogenesis of neoplastic cells, especially for people after illnesses, during the convalescence period. Undecan-2-ol is preferably used in the form of an additive to drugs, cosmetics and foodstuffs.

In nature, undecan-2-ol is present, inter alia, in Ruta graveolens herb oil, in Philodendron acutatum Scott root oil, in two varieties of curcuma Curcuma aeruginosa Roxb. and Curcuma heyneana Val., in Litsea odorifera oil, in cocoa butter, in sweet corn, and in many fruits, for example, fresh apples, bananas, strawberries.

The chemical synthesis of undecan-2-ol is based on the catalytic ketonization of acetic and decanoic acids in a flow system at a temperature of 400 ° C in the presence of MnO2 and Al2O3 oxides, and then reduction of undecan-2-one obtained in this reaction with sodium borohydride in isopropanol to undecane -2-ol. The ketonization process is 70% efficient, and the reduction is 91% efficient.

Undecan-2-ol is therefore an easily available compound with properties that allow it to be used as an ingredient in drugs, foodstuffs and cosmetics.

The following examples illustrate the subject matter of the invention.

P r z k ł a d I

In order to investigate the effect of undecan-2-ol on cellular and humoral defense mechanisms, 1% and 10% oil solutions of this compound were prepared and administered to 5 mice (Balb / c - weighing 25-28 g) inhaled for 1 hour. for 3 consecutive days. These solutions were administered as follows: 5 drops of the solution were put on a filter paper, and the paper was placed in a cage with mice, which was covered with a towel.

At the same time, another group of mice was not inhaled, but their cage was also covered with a towel (control group).

On the fourth day, the mice were anesthetized and bled to isolate the spleen for immunoassay. The test results are presented in Table 1 and Table 2. Means ± SD, n = 5, * means statistically significant P <0.05, ** means statistically significant P <0.01, compared to the control group parameters.

PL 210 209 B1

T a b e l a 1

Investigated immunological parameters Control group of mice 1% solution undecan-2-ol 10% solution undecan-2-ol Metabolic activity of blood phagocytes (RBA) (OD 620 nm) 0.35 ± 0.03 0.37 ± 0.04 0.53 ± 0.04 ** Intracellular killing activity blood phagocytes (PKA) (oD 620 nm) 0.31 ± 0.04 0.34 ± 0.05 * 0.48 ± 0.03 ** Proliferative activity of T lymphocytes (ConA) isolated from blood (OD 620 nm) 0.42 ± 0.03 0.45 ± 0.04 0.59 ± 0.04 ** Proliferative activity of T lymphocytes (ConA) isolated from the spleen (OD 620 nm) 0.47 ± 0.04 0.49 ± 0.05 0.68 ± 0.04 ** Proliferative activity of B lymphocytes (LPS) isolated from blood (OD 620 nm) 0.32 ± 0.02 0.34 ± 0.04 0.57 ± 0.04 ** Proliferative activity of B lymphocytes (LPS) isolated from the spleen (OD 620 nm) 0.39 ± 0.03 0.42 ± 0.04 0.64 ± 0.03 **

T a b e l a 2

Investigated immunological parameters Control group of mice 10% undecan-2-ol solution Metabolic activity of blood phagocytes (RBA) (OD 620 nm) 0.352 ± 0.04 0.51 ± 0.03 ** Intracellular killing activity of blood phagocytes (PKA) (oD 620 nm) 0.30 ± 0.03 0.45 ± 0.04 ** Proliferative activity of T lymphocytes (ConA) isolated from blood (OD 620 nm) 0.44 ± 0.03 0.57 ± 0.02 ** Proliferative activity of T lymphocytes (ConA) isolated from the spleen (OD 620 nm) 0.45 ± 0.04 0.65 + 0.03 ** Proliferative activity of B lymphocytes (LPS) isolated from blood (OD 620 nm) 0.35 ± 0.03 0.58 ± 0.03 ** Proliferative activity of B lymphocytes (LPS) isolated from the spleen (OD 620 nm) 0.38 ± 0.03 0.68 ± 0.04 ** Serum lysozyme activity (mg / l) 7.85 ± 0.45 9.80 ± 0.40 ** CRP (mg / l) 25.50 ± 2.55 26.9 ± 2.10 Ceruplasmin activity (IU) 19.5 ± 1.2 18.2 ± 1.6 Γ-globulin level (g / l) 9.25 ± 1.2 10.3 ± 1.5

As a result of the analysis of the research results, it was found that undecan-2-ol had a strong influence on defense mechanisms. Already at a concentration of 1%, it increased the activity of serum lysozyme, with no effect on acute-phase proteins and the level of gamma-globulin in the serum. It also increased phagocytamic and metabolic activity, as well as the ability to respond to ConA and LPS myogens of blood and spleen leukocytes.

P r z x l a d II

Studies of the effect of undecan-2-ol on antibody production were carried out on 10-12 week old female Balb / c and F1 Balb / cxDBA2 hybrids. Each mouse was administered intraperitoneally with 0.1 ml of a 10% sheep cell suspension (SRBC) and inhaled for 3 consecutive days with various concentrations of undecan-2-ol oil. For this purpose, a filter paper soaked in 5 drops of the solution was introduced into the cage with mice and the cage was covered with a cloth for 1 hour.

Simultaneously, the control group of mice was given a suspension of sheep blood cells, but not inhaled.

On the seventh day, the mice were anesthetized, bled, and serum levels of hemagglutinating antibodies to sheep erythrocytes were determined.

PL 210 209 B1

The test results are presented in Table 3.

T a b e l a 3

Number of mice Mean log titre +/- SE Significance of the difference in relation to the control group Control group of mice 10 7.5 +/- 0.20 - Undecan-2-ol 1% 5 10.4 +/- 0.24 P <0.001 Undecan-2-ol 10% 5 9.8 +/- 0.18 P <0.001

The analysis of the assay results shows that 1% undecan-2-ol showed a very strong stimulation of antibody production.

P r x l a d III

Studies on the effect of undecan-2-ol on the production of angiogenic cytokines by mouse spleen lymphocytes in vivo in the graft-versus-host test and in the syngeneic system were carried out on Baib / c inbred mice, F1 Balb / cxC3H hybrids and F1 female Balb / cxDBA2 hybrids at the age of 12 weeks weighing 25-28 g. Dormant mice were implanted intradermally into shaved skin of the back, splenic cells - 4-6 implants in one mouse, 500 thousand cells in 0.05 ml of Parker medium. The mice prepared in this way were inhaled for 3 days with undecan-2-ol solutions - filter paper impregnated with 5 drops of the test solution was introduced into the cage with 5 mice and the cage was covered with cloth for 1 hour.

At the same time, the control group of mice were implanted intradermally with spleen cells, but inhalation was not used.

The mice were then sacrificed with the Morbital hypnotic and the angiogenesis assay was read at the sites of cell implants on the inner skin surface using an operating microscope.

Cell donors were also inhaled in some experiments.

In some experiments, the sera of inhaled mice were collected and the concentration of pro-angiogenic cytokines bFGF and VEGF was determined by enzyme immunoassay ELISA.

Table 4 shows the effect of inhalation of recipients with undecan-2-ol on the angiogenesis test (LIA) in GVH response in mice, and table 5 shows the effect of inhalation of donors of splenic cells and sera on the activity of these cells in LIA recipients.

T a b e l a 4

Number of tests LIA Mean number of newly formed blood vessels +/- SE Significance of the difference in relation to the control group Control group of mice 51 17.5 +/- 0.28 - Undecan-2-ol 1% 18 24.5 +/- 0.80 P <0.001 Undecan-2-ol 10% 19 18.5 +/- 0.47 0.05> P <0.1 at the border

T a b e l a 5

Test material Number of LIA tests Mean number of blood vessels +/- SE Significance of the difference in relation to the control group 1 2 3 4 5 Control group of mice Spleen of recipient Balb / c mice 36 16.04 +/- 0.35 - Undecan-2-ol 1% Spleen of recipient Balb / c mice 40 16.1 +/- 0.28 irrelevant Control group of mice Balb / c serum, recipients Balb / c 9 24.8 +/- 1.2 - Undecan-2-ol 1% Balb / c serum, recipients Balb / c 10 13.5 +/- 0.62 P <0.001

PL 210 209 B1 cont. table 5

1 2 3 4 5 Control group of mice F1 spleen cells, recipient F1 10 17.4 +/- 0.58 - Undecan-2-ol 1% F1 spleen cells, recipient F1 10 14.6 +/- 0.61 P <0.01 Control group of mice The serum of recipient F1 mice 11 9.4 +/- 0.48 - Undecan-2-ol 1% The serum of recipient F1 mice 8 12.2 +/- 0.61 P <0.01 Control group of mice Mouse serum Balb / c, recipients of F1 11 11.4 +/- 0.32 - Undecan-2-ol 1% Mouse serum Balb / c, recipients of F1 10 13.9 +/- 0.40 P <0.01

The analysis of the assay results shows that in the experiments in which the recipients of cells were inhaled, the stimulation of angiogenesis was caused by 1% and 10% undecan-2-ol solution. In experiments where the donors of cells were also inhaled, the solution of undecan-2-ol caused stimulation in the syngeneic system (F1 to F1), while in the semi-allogeneic system (GVH) it did not influence the angiogenesis reaction. Balb / c mice sera induced significantly more vessels in syngeneic recipients than F1 mice sera, and undecan-2-ol inhalation lowered this induction. Thus, one can speak of an immunomodulatory effect of undecan-2-ol against sera, because inhalation of undecan-2-ol lowered high activity (Balb / c to Balb / c) and increased low activity (F1 to F1, Balb / c to F1).

P r x l a d IV

The effect of inhalation with undecan-2-ol solutions on the growth of Sarkom L-1 transplant sarcoma was assessed. For this purpose, cancer cells obtained from the cell bank of the Oncology Center in Warsaw were passaged 3 times in Balb / c mice, syngeneic for this tumor, and then implanted intradermally into anesthetized mice and inhaled for 3 consecutive days. After 72 hours, some of the mice were sacrificed and angiogenesis readings were made. The remaining mice, 5 days after cell implantation, were dissected and weighed nodules, and then subjected to routine histological processing.

It was found that both 1% and 10% undecan-2-ol solution strongly inhibited nodule development and angiogenesis.

Claims (2)

1. The use of undecan-2-ol as an immunostimulating agent, stimulating cellular and humoral defense mechanisms, the production of antibodies and the production of angiogenic cytokines, especially as an agent that inhibits the development and angiogenesis of neoplastic cells, especially for people with a history of convalescence. 2. The use according to claim 1 The process of claim 1, wherein undecan-2-ol is preferably used as an additive to medicaments, cosmetics and foodstuffs.