The method of obtaining water-soluble chitosan

 

(57) Abstract:

The invention is intended for use in medicine, veterinary medicine and cosmetics. Describes the method of obtaining water-soluble chitosan, comprising preparing a homogeneous solution of chitosan, its secretion by treatment with an alkaline agent to a pH of 6.9 and 7.5, the amorphization of chitosan in the form of the aqueous suspension in cavitation or mechanical fields with shear effects, the interaction of the resulting suspension with inorganic, organic acids or their anhydrides and isolation of the target product from solution in demineralized water using spray or freeze drying, characterized in that the used chitosan molefractions composition molecular weight (~100 kDa to-unit link - glucosamine) and degree of deacetylation from 68 to 95%) when the molar ratio of amine groups of all fractions of chitosan and inorganic acid of 1:(0.8 to 1), the amino groups of all fractions of chitosan and an organic acid of 1:(0,8-1,2), the amino groups of all fractions of chitosan and the anhydride of the organic acid of 1:(1-1,4). The technical result - environmentally friendly and efficient way to obtain without the use of organic solvents, extension spanie relates to the field of obtaining water-soluble chitosan and relates to the synthesis of a salt form of chitosan with various inorganic, organic acids and water-soluble derivatives of chitosan as a result of its reaction with anhydrides of carboxylic acids, which can be used in medicine, as a biologically active food supplements, veterinary and cosmetics.

Known methods of obtaining salt form of chitosan on the basis of mineral and organic acids for use in cosmetics, medicine and food industry [ed. mon. 419529. 08 IN 37/00. 15.03.74; the Japan patent 1152104 And 08 In 37/08, 14.06.89 and 1062302 And 08 In 37/08, 08.03.89; U.S. patent 5061792, 08 At 37/08, 29.10.91] and methods of obtaining water-soluble acylated derivatives of chitosan by its interaction with the anhydrides of organic acids [RF patent 2100373. 08 IN 37/08. Bull. 36 from 27.12.97; ed. mon. 508212, 08 At 37/08, Bull. 11 from 25.03.76].

The closest known solution is the method of obtaining succinate sodium salt of chitosan [RF patent 2144040 08 In 37/08. 07.04.98], characterized by efficiency and environmental cleanliness without the use of organic solvents and the use of acid-soluble chitosan with deacetylation (SD) 76% (range 74-82%) and srednevozrastnoe molecular mass (MM) 550 kDa (range 26-650 kDa) with a relatively narrow molecular weight distributed yousie and other properties significantly depend on the molecular characteristics - MM and SD. It is shown that the drugs based on chitosan with DM 70% have high biological activity, contribute to the activation of macrophages peritoneal exudates, natural killer cells, increase the production of antibodies and cleocinonline cytotoxicity [Nishimura K., Nishimura, S., Nishi N. Adjuvant activity of chitin derivatives in mice and guinea pigs. Vaccine - 1985. Vol. 3. 5. P. 375-384; Nishimura, K., Nishimura, S., Nishi N. Immunological activity of chitin and its derivatives. Vaccine - 1984. Vol. 2. 1. P. 93-99]. In addition, we discovered that these drugs activate the production of cytokines, such as interleukin-1, colony stimulating factor, interferon [K. Nishimura , S. Nishimura, H. Seo Macrophage activation with multi-porous beads prepared from partially deacetylated chitin. J. Biomed. Mater. - Res. - 1986. Vol. 20. 9. P. 1359-13721.

When studying the effect of chitosan on phage infection that his inactivating capacity increases with increase in the number of amino groups in the chitosan molecule (with increasing DM), reproduction coliphages effectively suppressed more high molecular weight chitosan [Kochkina H. M., Chirkov, S. N. Effect of chitosan on phage infection. Materials of the 5th Conf. "New perspectives in the study of chitin and chitosan". M: VNIRO may 25-27, 1999. S. 1511. Study of the sensitivity of microorganisms isolated from biopsies of the mucosa m is s was in direct correlation with MM and SD [Chervinets C. M., Mosquitoes B. A., S. Moskvin Century, Kurochkin A. A. Sensitivity of microflora in the stomach and duodenum to the chitosan and low-intensity laser radiation. Materials scientists. proc. "Herbal medicine and laser therapy in the 21st century". Chernogolovka RIO IPCP RAS 7-9 December 1999. S. 1051].

Especially note the lipotropic action of chitosan, opposing cardiovascular disease. Proposed antihyperlipidemic drug containing as an active ingredient oligomers of chitosan and/or chitin and does not cause side effects even with prolonged use [Japan's Bid 63-41422 from 06.08.86]. Lipotropic effect of chitosan was confirmed by scientists and our country [Tarasenko, A. Experimental substantiation of the hypocholesterolemic action of chitosan from shell crab. Materials of the 5th Conf. "New perspectives in the study of chitin and chitosan." M: VNIRO may 25-27, 1999. S. 198; Petrov, C. A., Tarasenko, A. Toxicological and higienica evaluation of chitosan from shell crab in chronic experiment. Ibid. S. 179].

The presence of water-soluble fractions of chitosan (MM-10 kDa that sootwetstwuet-60 units in the oligomeric chain) in preparations on its basis enhances the antitumor [patent I is 1956. A 61 K 31/73. 20.11.90 and 5912000. A 61 K 45/00. 15.06.99], promotes the healing of wounds [patent England 1252373. A 61 K 27/00 08 IN 19/14. 03.02.69; U.S. patent 3632754 17/00 a 61 K. 04.01.72 and 4772591 from 16.04.86].

An important quality of chitosan oral application (especially in the form of soluble forms complexes with acids or water-soluble derivatives [RF patent 2174000 from 22.02.2000] are its sorption properties, the ability to restore the gut and clean it the epithelium, preventing celias-the disease and its Gelato and complexing properties, providing linking and removal from the body of heavy metals, radionuclides, and various toxins, including anionic polymers. Chitosan in tens times more efficient ionoobmennye resin, all of these properties are directly dependent on the MM and DM chitosan.

Thus, the analysis of literary data and presents information leads to the conclusion that to expand the spectrum of positive action of chitosan-containing drugs and dietary supplements based on chitosan and its derivatives should be used chitosan molefractions composition in MM in the range from monomer (glucosamine) to ~150 kDa and diabetes in the limit is eghosa by mixing chitosan with different characteristics: 40-45 wt. % chitosan with MM 80-100 kDa and DM 80-85%; 45-40% chitosan with MM 80-100 kDa and DM 68-72%; of 7.0 to 6.0 wt.% chitosan with MM25 kDa and DM 80-85%; 8.0 to 7.0 wt.% chitosan with MM25 kDa and DM 68-72%; 0.0 to 2.0 wt.% oligomers of chitosan with the number of links in the chain from 1 to 10 and SD%, to obtain a water-soluble chitosan at a molar ratio of amine groups and an inorganic acid of 1:(0.8 to 1), amino and organic acids of 1:(0,8-1,2), amino groups and the anhydride of the organic acid of 1: (1-1,4), and chitosan with SD 80-85% (68-72%) and the desired value of MM is treated aqueous suspension of chitosan from the original MM 300-600 kDa hydrogen peroxide if necessary to obtain the specified value MM. The chitosan oligomers with N=1-10 treated chitosan aqueous phosphoric acid at a weight ratio of components: chitosan - phosphoric acid - demineralized water, respectively: 1:(0,4-0,6):(0,6-0,4) if 70oC for 4 hours, followed by neutralization and sublimation selection of the target product.

It is known that chitosan and its derivatives belong to progestacare polymers [RF patent 2144040 from 07.04.1998]. Heterogeneous degradation of these polymers depends on the degree of order (crystallinity), the values of MM and MMD, and the intensity of development under the influence of aggressive environments. M.: Chemistry. 1972. C. 72-78]. This phenomenon is due to diffusion availability destructible agent to the glycosidic linkages of chitosan [N. A. Plate, A. D. The Litmanovitch, O. C. Noah. Macromolecular reaction. M.: Chemistry. 1977 S. 47-51].

So for destruction under the action of hydrogen peroxide used svezhepriobretenny chitosan at pH 6.9 and 7.5, which is characterized by a low order and high availability glycosidic linkages [RF patent 2144040 from 07.04.1998].

It is known that hydrogen peroxide at pH ~7.0 and a temperature of 80oWith decomposes slowly in a large range of concentrations, and the rate of decomposition is a linear function of time [hydrogen Peroxide and peroxide compounds. Edited by Professor M. E. posina. L: GNTI chem. l-RA. 1951. S. 88-106]. Catalytic decomposition of hydrogen peroxide can be some enzymes of animal and plant cells, as well as ions of copper and iron, especially in a homogeneous environment, and under their joint presence, when the rate of decomposition can increase hundreds of times. Control of the concentration of metals in chitosan and its destruction in a heterogeneous environment allows to obtain reproducible data at concentrations: [H2ABOUT2]to 0.20 wt.%, [chitosan]3.0 wt.% and tempestuously chitosan under the action of hydrogen peroxide universal dependence of the degree of decomposition (DD - dgradation degree) from the process conditions [Sychuk A. C. Universal measure the depth of the degradation of the polymer. The logarithm of the relationship of molecular masses. RBM. Chem. Journe. So 57. 11. 1991. S. 1229]. Experimentally determined dependence DD=1n(M0/M)=f{[N2ABOUT2]}, where M0and M - srednevozrastnoe MM, respectively, the source and destruktivnogo acid-soluble chitosan [Gamzazade A. I., V. M. Slimak, Sklar A. M., Shtikova E. V., Pavlova S. V., S. V. Rogojin // Acta Polymerica. 1985. V. 36. 8. P. 420], the time in minutes, allows you to set conditions of degradation for a given MM target chitosan for any values of MM of the original polymer. Thus it is found experimentally that the value of the SD of chitosan at its heterogeneous decomposition under the action of peroxide of hydrogen does not change significantly.

Heterogeneous destruction swollen rigid or projectmanager polymer, as a rule, leads to reduction of MM and extension MMD because of the increased content of low molecular weight fractions of the polymer. This pattern is confirmed and chitosan. Studies exlusionary chromatography on device "Waters" with column firms Waters Ultrahydrogel-250 (7,8300 mm) showed that changing the relationship M0/M ~of 6.7 (DD=1,9) to~21,1 (DD=3,1) in the heterogeneous degradation of MMP fitosanitario increases by 20-30%. The evaluations showed that heterogeneous destructively chitosan with srednevozrastnoe MM ~80-100 kDa has a wide MMD: from ~ 150 kDa to water-soluble fractions, and with MM 25 kDa and ~50 kDa to glucosamine. Examination by means of GPC showed that the product of deep acid hydrolysis of chitosan consists of glucosamine and its homologues with the number of links in the chain of not more than 10.

Chitosan molefractions composition consisting of macromolecules with different number of links in the chain: from 1 (Monomeric link - glucosamine) to ~1000, obtained by combining the fractions of chitosan with different molecular characteristics. The amorphization of chitosan carry out selecting it by treating solutions of the alkaline agent to a pH of 6.8-7.5 and by treating the suspension of a mixture of fractions of chitosan in demineralizing water in cavitation or mechanical fields with shear effect realized when using a homogenizer brand MPW-302 (Poland) or mixer with high-speed (~ 1400 rpm) disk stirrer special design [RF patent 2144040 from 07.04.1998] that allows you to create cavitation and mechanical fields with shear effect on the working volume.

Tests of water-soluble forms prefractal practice chitodes in pure form and in combination, first infusions fees medicinal plants, and then with dry extracts of various charges have revealed high efficiency of the proposed composition of the chitosan in the prevention and treatment of various diseases [Chervinets C. M., Bogatov centuries , Soloviev, C. A., SAMINA S. A., Petrov, M. B., Komarov A. B. Method of increasing the sensitivity of bacteria to biodestruction the action of laser radiation in combination with a photosensitizer. RF patent 2151601 from 09.09.1999; Chervinets C. M., Komarov A. B. treatment of chronic gastritis, gastric ulcer and duodenal ulcer. RF patent 2150271 from 13.10.1999; Treskunov K. A. , Komarov A. B. a Method of treatment of cancer. RF patent 2165253 from 20.01.1998; Chervinets C. M., Bogatov centuries, SAMINA S. A., Komarov A. B. Method of local treatment of acute prostatico. RF patent 2153318 from 13.10.1999; Treskunov K. A., Komarov A. B. Method of treatment of bronchial asthma. RF patent 2172634 from 18.08.1998; Pogorelsky L. C., Treskunov, K. A., tracina I. P. Komarov, B. A., Turanov M. H., Petrov E. C. treatment of infectious diseases. RF patent 2174000 from 22.02.2000]. These circumstances demonstrate compliance of the proposed technical solution the criterion of "novelty".

Due to the fact that water-soluble forms of chitosan molefractions composition can use supplements, it is important to note the toxicity and biological activity of the resulting product. As domestic researchers [K. D. Zhogolev, C. Y. Nikitin, V. N. The Gypsies. Drugs based on chitin, chitosan in medicine and a balanced diet. Series: Medicine for the 21st century. C. IB. 2000. C. 6] and foreign [S. S. Davis, Illum. Chitosan for drug delivery oral route. In kN. "Chitosan per os. From food additives is a drug". /Edited by Riccardo A. A., Muzzarelli/ Nizhny Novgorod: Publishing house "Vector - Tis". 2001. S. 187] note low toxicity of chitosan in oral application. The toxic property of chitosan is evident in the case of reception in the amount of greater than 18 g / day per 1 kg of body weight of the mice. It does not distinguish between samples of chitosan with different molecular characteristics [K. D. Zhogolev, C. Y. Nikitin, V. N. The Gypsies. Drugs based on chitin, chitosan in medicine and a balanced diet. Series: Medicine for the 21st century. C. IB. 2000. C. 17]. The lack of toxicity of chitosan observed with intramuscular or intraperitoneal administration. A study of 30 samples of chitin and chitosan with MM from 50 to 300 kDa and 9 and their low molecular weight water-soluble derivatives found their toxic action only when administered intravenously [Koval Y. F., J. the curtain and their derivatives // improvement of the production of chitin and chitosan from pancreatectomy waste krill and ways of their use. M. 1992. S. 30-36].

Using labeled substance3H-chitosan and chitosan, labeled with technetium-99m, the authors of [S. S. Davis, Illum. Chitosan for drug delivery oral route. In kN. "Chitosan per os. From food additives is a drug". / Edited by Riccardo A. A., Muzzarelli / Nizhny Novgorod: Publishing house "Vector - Tis". 2001. S. 187] could not find transportation chitosan through nasal mucosa into the bloodstream. But for oral use [B. A. Komarov, A. I. Albulov, D. A. Estrin, Y. I. Estrin, N. A. Shevchenko, R. I. Dad's, Century, Kostyuk. The efficiency of chitodes and phitochitodes as a promising biologically active food additives. Proceedings Of The 6th Int. proc. "New advances in the study of chitin and chitosan" M - Shchyolkovo. Ed. VNIRO. 2001. S. 195] found rapid (3 min) penetration oligomeric3H-chitosan not only in blood but also in various organs. It is essential that when using3H-chitosan with MM~87 kDa ceteris paribus also found chitosan in the blood and various organs, but in this case, the maximum content in the blood is reached after 15 minutes and is lower by 1.7 times compared with the oligomeric 3H-chitosan.

This information is important for understanding the immuno which social research has established, what drugs chitosan cause a significant increase in activity of enzymes of glycolysis, hexosaminidase shunt and the Krebs cycle, activate the phagocytosis of microorganisms, increase the number of migrating phagocytes in the focus of inflammation [K. D. Zhogolev, C. Y. Nikitin, V. N. Roma, V. N. Egorov. The development and study of some dosage forms of drugs based on chitosan. Proceedings Of The 6th Int. proc. "New advances in the study of chitin and chitosan" M - Shchyolkovo. Ed. VNIRO. 2001. S. 165; K. D. Zhogolev, C. Y. Nikitin, V. N. The Gypsies. Drugs based on chitin, chitosan in medicine and a balanced diet. Series: Medicine for the 21st century. C. IB. 2000; L. Gorovoj, O. Seniouk, G. Beketova, N. Savichuk, G. Amanbaeva. The use of chitin-containing drug Mycoton in pediatric gastroenterology. In kN. "Chitosan per os. From food additives is a drug". /Edited by Riccardo A. A., Muzzarelli/ Nizhny Novgorod: Publishing house "Vector-Tis". 2001. C. 241].

Let's consider another aspect of the manifestation of biological activity of chitosan is its bacteriostatic properties. Extensive research conducted on the microbial contamination of the mucous membrane of the gastroduodenal zone in biopsies taken at fibrogastroduodenoscopy of periultseroznoy zone, enthralling the second colon, and from the mucosa of the lower third of the esophagus of patients with esophagitis using chitosan with MM from 26 to 600 kDa, helped to set a high antimicrobial activity of chitosan in the studied range MM - from 58 to 85% of the organisms are sensitive to all samples of chitosan [C. M. Chervinets. Change of microflora in inflammatory and erosive-ulcerative lesions of the esophagus, stomach and duodenum and its correction. Thesis for the academic degree of doctor of honey. Sciences. M 2002; C. M. Chervinets, V. M. Bondarenko, A. I. Albulov, B. A. Komarov. The antimicrobial activity of chitosan with different molecular weight. Proceedings Of The 6th Int. proc. "New advances in the study of chitin and chitosan" M - Shchyolkovo. Ed. VNIRO. 2001. S. 252]. Found a trend of increasing antimicrobial activity of chitosan with the increase of diabetes. The greatest sensitivity of the isolated microflora from a lesion of the mucous membrane of esophago-gastroduodenal found to samples of chitosan with 320-350 MM kDa (82-87%).

Clinical trials conducted in the Institute of nutrition Russian Academy of medical Sciences in 1996, allowed us to conclude that taking food SUPPLEMENTS "Chitosan food" on the background of a low-calorie hyponatriemia anti-sclerotic diet spasams,2% in the control group of patients, revealed pronounced hypolipidemic effect: reduction of cholesterol and triglycerides in the serum of patients experienced group 19% (against 10% and 12% in control) resulted in lower levels of bilirubin in the serum 3 times greater than that of the control group patients. The latter in combination with a cholesterol-lowering effect indicates the presence of a choleretic action of chitosan.

Based on data presented, we can conclude that the immunostimulatory effects of drugs on the basis of chitosan molefractions composition will be determined oligomeric water-soluble fraction of chitosan and bacteriostatic antimicrobial properties - the presence of high-molecular fraction of chitosan, which can dissolve only in acidified water.

The proposed method of producing chitosan molefractions composition tested in laboratory and industrial conditions. Currently manufactured an experimental batch of different food SUPPLEMENTS on the basis of dietary chitosan molefractions composition.

The invention is demonstrated by the following examples.

Example 1. 515,5 g of chitosan with MM ~600 kDa and DM 68-72% dissolved under stirring for 4 h at aprooval mesh to remove insoluble impurities, which content is 3 wt.%. To the resulting solution while stirring, slowly add 8,02 kg 2.5 wt.% NaOH solution in demineralized water and adjusted pH to 6.8. Landed chitosan was filtered using a special filter from Bellington diagonal weave, washed with demineralized water and wring out, get 500 g svezheproshitogo chitosan in the form of 5.5 wt.% suspension. The resulting suspension is loaded into an enamel or glass reactor with a capacity of ~25 l, diluted with demineralized water to a concentration of 3 wt.%, heated to a temperature of 80oTo add the hydrogen peroxide at the rate of 0.15 wt.% the total weight of the suspension and with intensive stirring and incubated for 25 min, then filtered, washing with cold demineralized water (17-20 l). The resulting suspension to wring out of chitosan content of 7.2-7.5 wt.%. Losses are practically absent. Destructively chitosan has a MM ~80 kDa, SD ~ 68-72%.

Example 2. Analogously to example 1, but take for dissolving chitosan with MM 300 kDa and DM 80-85%, at planting NaOH solution pH was adjusted to 7.5, the suspension svezheproshitogo chitosan is treated with a hydrogen peroxide concentration of 0.2 wt. % within 34 minutes Get hit% load in an enamel or glass reactor with a capacity of ~ 2 l, add 500 g of 60 wt.% orthophosphoric acid in demineralized water (density of solution 1,426 g/ml), which corresponds to the relationship: chitosan - phosphoric acid - demineralized water, equal to 1-0,6-0,4. Then heated under stirring and the temperature at 70oC for 4 h After cooling portions with vigorous stirring add calcium hydroxide to a pH of 4, again cooled, filtered, adjusted pH to 7.0-7.5 and advocate for at least 12 hours Then decanted and the aqueous solution lyophilizer. The output of the oligomers with the number of links in the chain from 1 to 10-67 g, or to 13.4 wt.%, SD 95% (267 g of 25 wt.% solution of oligomers in demineralised water). Used in dry form or in solution.

Example 4. Analogously to example 3, but take 500 grams of chitosan with MM 25 kDa, SD 80-85% (68-72%), add 500 g of 40 wt.% orthophosphoric acid in demineralized water (density of solution 1,254 g/ml). The output of chitosan oligomers from the monomer to datatimer ~100 g, or ~20 wt.%, SD 95% (400 g 25 wt. % solution of oligomers in demineralised water).

Example 5. In an enamelled vessel with a volume of 8 l dissolve of 37.7 g of L-glutamic acid in 3 l of demineralized water at 40oC and stirring with a homogenizer brand MPW-302 (P is x and mechanical fields with shear effect on the working volume of a La carte add sample fractions of chitosan: 400 g of a suspension of chitosan, 7.2 wt. %, (28.8 g) MM 80-100 kDa and DM 80-85%; 450 g of a suspension of chitosan, 7.2 wt. %, (32,4 g) MM 80-100 kDa and DM 68-72%; 70 g of a suspension of chitosan, 7.2 wt. %, (5,04 g) MM 25 kDa and DM 80-85%; 80 g of a suspension of chitosan, 7.2 wt. %, (5,76 d) MM 25 kDa and DM 68-72% in accordance with a molar ratio of L-glutamic acid and NH2groups of all fractions of chitosan, equal to 0.8:1, and stirred to dissolve within 1.5-2 minutes the resulting solution is frozen and lyophilizers. After lyophilization crushed and tabletirujut. Output 97-98 wt.%.

Example 6. Analogously to example 5, but take succinic acid at a molar ratio to the NH2groups of all fractions of chitosan, equal to 1.2:1, and the fraction of chitosan: 450 g of a suspension of chitosan, 7.2 wt.%, (32,4 g) MM 80-100 kDa and DM 80-85%; 400 g of a suspension of chitosan, 7.2 wt.%, (28.8 g) MM 80-100 kDa and DM 68-72%; 60 g of a suspension of chitosan, 7.2 wt.%, (4,32 d) MM 25 kDa and DM 80-85%; 70 g of a suspension of chitosan, 7.2 wt.%, (5,04 g) MM 25 kDa and DM 68-72% and USD 5.76 g of a solution of chitosan oligomers, 25 wt.%, (1.44 g) with the number of links in the chain from 1 to 10 and SD 95%.

Example 7. Analogously to example 5, but take hydrochloric acid at a molar ratio of NH2groups of all fractions of chitosan, which is 1:1.

Example 8. Analogously to example 7, but take molar ratio of hydrochloric acid to NN IS M 80-100 kDa and DM 80-85%; 400 g of a suspension of chitosan, 7.2 wt.%, (28.8 g) MM 80-100 kDa and DM 68-72%; 70 g of a suspension of chitosan, 7.2 wt.%, (5,04 g) MM 25 kDa and DM 80-85%; 70 g of a suspension of chitosan, 7.2 wt.%, (5,04 g) MM 25 kDa and DM 68-72% and 2.88 g of the solution of chitosan oligomers, 25 wt.%, (0,72 g) with the number of links in the chain from 1 to 10 and SD 95%.

Example 9. Analogously to example 5, but the amorphization of a mixture of fractions of chitosan carried out using a mixer with high-speed disk stirrer special design that allows you to create cavitation and mechanical fields with shear effect on the working volume. In the process of amorphization to the mixture of fractions of chitosan add powder succinic anhydride with a particle size of 100 μm when the molar ratio of NH2groups of all fractions of chitosan, which is 1:1.

Example 10. Analogously to example 9, but add to the mixture fractions of chitosan powder succinic anhydride with a particle size of 100 microns at its molar ratio to the NH2groups of all fractions of chitosan, is 1.4:1.

The concentration of NH2groups in chitosan molefractions composition consisting of a mixture of n-fractions are calculated according to the formula: [NH2] = SUM(GnSDn)/(n100), where Gnand SDnaccordingly dry weight in g and deacetylation Yun= 203-(CDn)/100.

Found in clinical practice, high efficiency chitodes to a certain extent due to partial penetration of chitosan in the blood and various organs. Consider this question in more detail. The fact the absorption of chitosan and its excretion is installed on a quantitative level, with a special study of the dynamics of the penetration and removal of oligomers3H-chitosan with the number of links in the chain from 1 to 10 in the blood and various organs of male mice of line C-57/MO. Oligomer3H-chitosan was administered per os in the form of a solution in water at a dose of 4 mg/kg of body weight of the animal (~100 μg per animal), which corresponds to the reception 5-7 times a day, double the dose for a person weighing 70 to 90 kg (1 dose of chitodes equal to 25 mg).

It turned out that the most active3H-chitosan enters the liver, where the maximum content of 1.2 wt.% from the input) is detected within three minutes after oral administration, then the content of chitosan initially decreases rapidly (up to ~15 min), then smoothly (up to 20 hours). Note that in the blood and organs3H-chitosan detected already after 1 min after injection. It is essential that qualitative test soluble 3H-chitosan with MM 87 kDa and is in their blood and various organs, but in this case, after 15 min of its content in the blood ~ 1,7 p less compared to oligomeric 3H-chitosan in equal doses and conditions introduction, in the future, the blood levels of these two types of3H-chitosan is aligned. The content of acid-soluble3H-chitosan in the liver 15 min after injection three times less than oligomeric3H-chitosan. It is obvious that by changing the content of oligomeric fractions (1 to 10 links in the chain) in the chitosan molefractions structure it is possible to regulate the degree of penetration of it in the blood and various organs.

The research continues. But we can already conclude that found many different scholars and schools of the properties of edible chitosan due to its ability to partial rapid digestion and absorption in the blood and various organs subject to the availability of, apparently, the chitosan is similar to the oligomeric fraction. This fact may underlie a variety of positive effects in clinical practice chitodes and phytochitodes.

In addition, the efficiency of chitodes may be due to important as solubility in water, saliva. Oral use only moderately weakly alkaline (7<pH 25 kDa and DM 80 - 85%; 8.0 to 7.0 wt. % chitosan with MM 25 kDa and SD 68 - 72%; 0.0 to 2.0 wt. % of chitosan oligomers with number of links in the chain of 1 - 10 and SD 95%.

 

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