Method for preparing high-purity 68ga solutions

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to methods for preparing 68Ga solutions which involves the following stages: reaction of 68Ge/68Ga generator eluate and cation-exchange resin, washing of cation-exchange resin in the mixture of 0.2-1 M hydrochloric acid and 20-80 vol. % of acetone, eluation of 68Ga with cation-exchange resin by the mixture of 1.8-2.5 M hydrochloric acid and 20-80 vol. % of acetone, reaction of the prepared eluate and anion-exchange resin, washing of anion-exchange resin in an organic solvent, drying of anion-exchange resin by air and neutral gas and eluation of 68Ga with anion-exchange resin by an aqueous solution of 0.01-0.1 M hydrochloric acid wherein it's amount is 15-25 less than that of the initial 68Ge/68Ga generator eluate. EFFECT: method provides preparing the concentrated solutions of the 68Ga radionuclides of high chemical and radiochemical purity containing no organic solvents that enables preparing the 68Ga radiopharmaceutical of high molar activity and radiochemical purity.

2 cl, 3 tbl, 2 dwg, 4 ex

 

The invention relates to medicine, in particular to methods for solutions of68Ga high purity using radionuclide generator68Ge/68Ga, and can be used for the synthesis of radiopharmaceuticals (RN)used in positron emission tomography (PET).

Radionuclide68Ga obtained from radionuclide generator68Ge/68Ga [1]by the totality of the nuclear-physical and chemical properties, is one of the most promising for the synthesis of radiopharmaceuticals used in PET. Great half-life of the parent68Ge provides the long life of the generator. In turn, the small half-life68Ga (T½ ,=68,1 min) allows the use of radiopharmaceuticals required activity without creating significant radiation doses to the patient. In addition, the cation68Ga can form stable complex compounds with many ligands containing oxygen, nitrogen and sulfur as the atoms of the donor, making it suitable for synthesis of a large number of chelate complexes of macromolecules of different functional purposes. Most of the labeled molecular imaging agents include ligand system is a bifunctional chelating agent (BHA), which binds the radionuclide and contains a functional group capable of binding the b complex biomolecules. The most significant polydentate representatives bifunctional chelating agents are acyclic ligands N,N'-bis(2,2-dimethyl-2-mercaptoethyl)Ethylenediamine-N,N'-dioxyna acid (6SS), Tris-aminomethylated (TAME), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and deferoxamine (DFO), and macrocyclic 1,4,7-triazacyclononane-N, N', N"-trioxane acid (NOTA), 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraoxane acid (TETA) and 1,4,7,10-tetraazacyclododecane-N, N', N", N"'-tetraoxane acid (DOTA) and derivatives thereof. These chelating agents are well studied and successfully used in the synthesis bioconjugates included in RN. Their use and synthesis described in the scientific literature and is protected by several patents [2-13].

The chemical form68Ga in the eluate generator68Ge/68Ga means, theoretically, its universal and direct use in the preparation of the RFP, subject to the availability of a suitable chelating agent. However, the presence of competing chemical impurities in the eluate prevents the formation of complexes68Ga3+. The presence in the working solution of impurities Cd2+;2+; Cu2+; In3+; Fe2+; Fe3+; Lu3+; Ni2+; Zn2+already in quantities of 1 μm is unacceptable for qualitative RN [5]. Breakthrough dolgozhivuscikh the parent 68Ge through the column with sorbent is 10-2-10-3% of total activity68Ge generator at the time of elution. In addition, a sufficiently large volume (5 ml) of the eluate generator requires concentration activity for tagging nanomolar quantities bioconjugates. Thus, purification and concentration of the eluate generator68Ga are the necessary procedures before the actual reaction tagging bioconjugates.

A method of obtaining chemically and radiochemically pure radionuclide68Ga [6], according to which Frank Rosch and Konstantin P. Zhemosekov with co-workers proposed the use of cationic exchange for purification and concentration of the eluate generator68Ge/68Ga. By the described method the eluate generator68Ge/68Ga is in the interaction with the cation exchange resin Dowex 50W×8, then the68Ga eluted from the cation exchange resin with a mixture of hydrochloric acid and acetone. This method protected by the patent [7]. The claimed method allows to obtain a purified and concentrated solution of the radionuclide68Ga 400 ál in a mixture of 0.05 M Hcl/97.6% of acetone with a yield of more than 97% of the initial activity68Ga (including decay). Thus obtained solution was used directly for the reaction tagging bioconjugates. The claimed method is characterized by simplicity re the implementation, fast, high concentration and high yield68Ga, high efficiencies from non-isotropic media (Zn2+, Fe3+, Ti4+) and can be successfully applied for the synthesis of labeled68Ga PET markers [8]. However, obtaining labeled compounds practically in acetone solution makes it impossible to use for clinical purposes directly after the reaction tagging. Therefore, after the reaction tagging synthesized RN must undergo solid-phase extraction for the removal of acetone and improve the radiochemical purity. The use of solid phase extraction lengthens the process of synthesis of prepared radiopharmaceuticals (resulting in loss of short-lived radionuclide) and entails the presence of ethyl alcohol in the finished product, which is also undesirable. A method of obtaining chemically and radiochemically pure radionuclide68Ga proposed Velikan, Blogstream (Irina Velikyan, Bengt Långström), etc. This method includes a step of purification and concentration of the eluate generator68Ge/68Ga using anion-exchange resin-based politicalgovernmental containing HCO3-as the counterions and the functional group Quaternary amine. According to the described technology [9] the eluate generator68Ge/68Ga smachivaetsya concentrated hydrochloric acid (to bring the concentration of Hcl up to 4-5 M). The resulting solution is in the interaction with the anion-exchange resin-based politicalgovernmental including VAT3-as the counterions and the functional group Quaternary amine. More than 99%68Ga while held in the resin and can be subsequently suirvey 200 ml of pure water. The method is characterized by speed, high concentration and high yield68Ga, high efficiencies from non-isotropic media (Zn2+, Fe3+, Ti4+) and can be successfully applied for the synthesis of labeled68Ga PET markers. The disadvantages of this method include the use of concentrated hydrochloric acid (which requires the use of particularly resistant construction materials), as well as the fact that when the elution68Ga with anion-exchange resin with water after concentratewanna hydrochloric acid is extremely difficult to control the pH of the final solution (due to the presence of residual acid on the resin, the concentration of Hcl in the final solution can be greater than 0.1 M, which makes the solution suitable for the reaction tagging bioconjugates).

There is a method of allocating children radioisotope68Ga, substantially free from impurities of the parent radioisotope68Ge [12], using the apparatus comprising the first number of the TCU with the sorbent, containing parent68Ge and child68Ga, the source of the first eluent, connected with the first column to highlight child68Ga from the first sorbent; the first eluent contains citric acid that is separated gallium exists in the form of gallium citrate, which in the mixing chamber is mixed with concentrated hydrochloric acid. Gallium citrate is converted to gallium tetrachloride, which is adsorbed in the second column, and then eluted with water or a weak buffer solution for subsequent labeling of the target molecules with final purification of the product on the third column. The disadvantages of this method are as mentioned above the use of concentrated hydrochloric acid (which requires the use of highly resistant structural materials). It also uses a rather complicated three - step purification scheme, and the question of refinement of metals is not considered, and the corresponding data are not presented.

The closest in technical essence and the achieved result is a method of obtaining solutions68Ga using a system consisting of two columns containing cation exchange resin and anion exchange resin [13]. In the first column68Ga adsorbed from a solution of 0.1-0.5 M Hcl (in the example, 0.5 M) on the strongly acidic cation exchange resin (AG 50W×8), a68Ge passes through the column. For more the complete separation 68Ge column was washed with 0.5 M Hcl. For desorption68Ga use a 4 M solution of Hcl. From this solution68Ga sorbed in the second column on the UTEVA resin (diamyl[Jamil]phosphonate). For desorption68Ga is used 2-5 ml of 0.1 M Hcl. The process time 22 min Output68Ga with regard to the collapse of 95%, the impurity of the parent68Ge in the product is less than 10-7%. As an option in order to save time it is proposed to use a single column with anion exchange resin and lead sorption68Ga on the anion of 8 M Hcl solution, but in this case it is impossible to get such a high level of purification from68Ge. The disadvantage of the method the authors note the high content in the product of calcium and phosphorus, which, apparently, partially washed out of the material of the anion. In addition, as in the above-described methods, in this case it is necessary to use relatively concentrated solutions of Hcl. The disadvantages of the method can also include a relatively large volume (2-5 ml) of the obtained product, i.e. the task of concentrating the eluate generator68Ge/68Ga in this way is not solved.

The aim of the invention is to develop a new method of obtaining solutions68Ga high purity, which allows to obtain concentrated solutions68Ga high chemical and radiochemical purity, containing no PR is hanicheskih solvents, which can be used for the synthesis of radiopharmaceuticals with high specific (molar) activity and radiochemical purity in the most convenient for clinical use form.

As a result of experimental studies, we have developed a method of obtaining solutions68Ga high purity using ion exchange technology, providing the possibility of reducing the content of radionuclide impurities68Ge two to three orders of magnitude, and the content of chemical impurities on 1-4 order while concentrating solutions68Ga in 15-25 times.

To achieve this goal solution68Ga high purity was obtained in accordance with the flowchart presented in figure 1. According to the block diagram of the generator eluate68Ge/68Ga (5 ml 0.1 M Hcl) was applied for the first column of strongly acidic cation-exchange resin, which68Ga was quantitatively sorbirovtsa. In this part of chemical impurities contained in the eluate, and the parent radionuclide68Ge on the cation exchanger was not late. Then most of the sorbed on the cation exchange resin chemical impurities (Zn2+In3+, Cr3+,

Cu2+Cd2+, Pb2+Sn2+, Al3+and others) were quantitatively suirable when washing the cation exchange resin with a mixture of hydrochloric acid and acetone (volume concentration of hydrochloric acid from 0.2 to 1 is, volumetric content of acetone from 20 to 80%), with68Ga with the cation exchanger was not elyuirovaniya. After washing68Ga quantitatively and almost was selectively suirable with the cation exchange resin with a mixture of hydrochloric acid and acetone (volume concentration of hydrochloric acid from 1.8 to 2.5 m, the volumetric content of acetone from 20 to 79%). The obtained eluate was directed to the second column of strongly basic anion-exchange resin, which was quantitative sorption of68Ga. With2+, Ti4+, Mn2+, Ni2+and some other impurities were not barbirollis. To completely remove traces of acetone and hydrochloric acid anion-exchange resin was washed with ethyl alcohol or other suitable organic solvent and dried air or inert gas. After which68Ga was quantitatively suirable with anion-exchange resin 200-300 µl of hydrochloric acid with a concentration of 0.01-0.1 M Thus, the original solution68Ga was concentrated in 15-25 times. The result has been purified and concentrated solution of chloride complexes68Ga in hydrochloric acid with a concentration of 0.01-0.1 M, suitable for direct use in the labeling reaction. Synthesized using the obtained solutions RN68Ga was characterized by a high radiochemical purity (>95%).

Figure 1 shows the block diagram of the process receive the deposits of solutions 68Ga high purity; figure 2 is a chromatogram of the reaction mixture when the reaction tagging with the original eluate of genrator68Ge/68Ga and purified solution68Ga.

Example 1.

Cleaning the model solution. Using salt (chlorides) metals and hydrochloric acid concentration of 0.1 M, cook the model solution. The metal content in the model solution shown in table 1.

Table 1
The metal content in the model solution
Concentration, ug/l
LiLi0,35
AluminumAl14000
TitaniumTi18000
VanadiumV14
ChromeCr7700
ManganeseMn7600
Cobalt Co3,3
NickelNi16000
CopperCu15000
ZincZn9500
GermaniumGe2000
ArsenicAs2,8
StrontiumSr3,6
ZirconiaZr11000
CadmiumCd13000
IndiesIn5600
TinSn7900
AntimonySb4,2
TelluriumThe0,54
ThalliumTl0,11
LeadPb9500
BismuthBi1
GalliumGa18000

The resulting solution was passed through a column containing ion exchange resin Dowex AG 50W×8 (H+form (200-400 mesh). The amount of the missed solution - 5 ml column Then washed with hydrochloric acid and acetone (0.5 M Hcl/50% vol. acetone), and then pass 5 ml of hydrochloric acid and acetone (2 M Hcl/70% vol. acetone). With the help of hydrochloric acid with a concentration of 2 M bring the ratio of hydrochloric acid and acetone in the eluate to the value (2M Hcl/44 vol.% acetone). The resulting solution was passed through a column of anion exchange resin containing ion-exchange resin Dowex 1×2 in CL--form. Then a column of anion exchange resin is washed with 5 ml of ethyl alcohol. Through the washed column skip the solution of 0.1 M Hcl.

Table 2
The degree of purification of the model solution
Concentration, ug/lThe purification coefficient, K=C1/C2/sub>
before cleaning, C1after cleaning, With2
LiLi0,350,057
AluminumAl1400020700
TitaniumTi1800059305
VanadiumV1427
ChromeCr770025031
ManganeseMn760018,2418
CobaltCo3,30,5546
NickelNi160009,5 1684
CopperCu15000467,632
ZincZn950030317
GermaniumGe20000,1315385
ArsenicAs2,80,214
StrontiumSr3,60,218
ZirconiaZr110001,66875
CadmiumCd1300030,6425
IndiesIn56000,414000
Tin Sn7900320,725
AntimonySb4,20,0670
TelluriumThe0,540,0154
ThalliumTl0,110,00814
LeadPb950042375
BismuthBi10,0520
GalliumGa1800017350

The resulting eluate is collected and analyzed for metals by the method of inductively coupled plasma mass spectrometry (ICP-MS). The results of the analysis, and the calculated values of the coefficients To clean are shown in table 2.

Analyzing the data presented in table 2, m is tenderly to conclude, the model solution of gallium has been considerably cleaned, losses Ga amounted to only 3.6%.

Example 2.

Purification of the eluate generator68Ge/68Ga. To obtain the solution68Ga use generator68Ge/68Ga (1850 MBq from 17.06.2009). For elution using 0.1 M Hcl. The volume of the eluate with 5 ml. of Activity at the time of elution - 435 MBq. (0.5 ml of the eluate is taken for analysis for metals and the breakthrough of the parent radionuclide68Ge). The resulting eluate is passed through a column of cation exchange resin containing ion-exchange resin Dowex AG 50W×8 in the N4form (200-400 mesh). Then the column was washed with 5 ml of hydrochloric acid and acetone (0.5 M Hcl/50% vol. acetone). Through the washed column skip to 1 ml of hydrochloric acid and acetone (2M Hcl/44 vol.% acetone). The resulting eluate is passed through a column of anion exchange resin containing ion-exchange resin Dowex 1×2 in CL-form, after which the column is rinsed with argon for 5 minutes Then through a column of anion exchange resin miss 300 μl of 0.1 M hydrochloric acid. The resulting eluate is collected. Measure the absolute activity. Analyze for metals. The activity of the obtained eluate after 17 minutes after elution of the generator68Ge/68Ga is 358 MBq. The output of the cleaning process without taking into account the decay is 82%, taking into account decay - 98%. The results of anal is for the content of metals (atomic absorption analysis) source and purified eluate is presented in table 3.

1,8×10-7
Table 3
The degree of purification of the eluate generator68Ge/68Ga
Source (µg/ml)Cleared (µg/ml)ToPTS
Zn52475301750
Fe3951658681
C8343471775
Ti218924,2
Al6815911,5
Ni4802519,2
Cr69000203450
68Ge/68Ga, %of 3.2×10-3

Thus, the application of the developed method of purification of the eluate generator68Ge/68Ga has allowed to obtain a concentrated solution68Ga high purity.

Example 3.

Purification of the eluate generator68Ge/68Ga.

To obtain the solution68Ga use generator68Ge/68Ga (1850 MBq from 17.06.2009). For elution using 0.1 M Hcl. The volume of the eluate with 5 ml. of Activity at the time of elution - 380 MBq. The resulting eluate is passed through a column of cation exchange resin containing ion-exchange resin Dowex AG 50W×8 in the N+form (200-400 mesh). Then the column was washed with 5 ml of hydrochloric acid and acetone (0.5 M Hcl/50% vol. acetone), and then pass 5 ml of hydrochloric acid and acetone (2 M Hcl/70% vol. acetone). With the help of hydrochloric acid with a concentration of 2 M bring the ratio of hydrochloric acid and acetone in the eluate to the value (2M Hcl/44 vol.% acetone). The resulting solution was passed through a column of anion exchange resin containing ion-exchange resin Dowex 1×2 in CL--form. Then a column of anion exchange resin is washed with 5 ml of ethanol, after which the column is rinsed with argon for 5 minutes washed Through the column pass 300 μl of a solution of 0.01 M Hcl. The activity of the obtained eluate after 20 min after elution of the generator68Ge/68Ga is 294 MBq. The output process is as clean without taking into account the decay - 77%, taking into account decay - 95%.

Example 4.

The preparation of radiopharmaceuticals.

1 ml of the original eluate generator68Ge/68Ga and obtained by the present method, as described in Example 2, concentrated and purified solution68Ga add 2 bottle with lyophilisate, consisting of 10 mg of sodium acetate and 20 μg of the peptide DOTA-TATE. Then the reaction mixture in vials thermostatic at a temperature of 95°C for 10 min, the Yield of the reaction tagging (radiochemical purity of the drug) is 44% for the source of the eluate and 98% when using concentrated and purified solution68Ga (method of analysis - radiooncology chromatography on plates ITLC SG, mobile phase 0.05 M citric acid). Chromatographic analysis shows (figure 2)that result from the use of the proposed method of obtaining solution68Ga high purity prepared radiopharmaceuticals with high radiochemical purity.

Sources of information

1. RU # 2126271 C1, 20.02.1999.

2. Meyer, G.J., H.Macke, J.Schuhmacher, W.H.Knapp and .Hofmann.68Ga-labelled DOTA-derivatised peptide ligands, Eur. J.Nucl. Med. Mol. Imaging (2004)31:1097-1104(2004).

3. WO 2005/057589 A2, 23.06.2005.

4. Maecke, H.R., .Hofmann, and U.Haberkom.68Ga-Labeled Peptides in Tumor Imaging, J. Nucl. Med. 46:172S-178S (2005).

5. Breeman W.A.P., de Jong M, Blois E, Bernard BF, Konijnenberg M, Krenning E.P.; Radiolabelling of DOTA-peptides with68Ga. Eur. J. Nucl. Med. Mol. Imaging. - 2005. - V.33. - P.478-85.

6. Zhemosekov K.P., Filosofov DV, F.Rosch et al. Processing of generator-produced68Ga or medical application. J. Nucl. Med. - 2007. - Vol.10. - P.1741-1748.

7. DE 102004057225 B4, 12.10.2006 (EP 000001820197, WO 002006056395, US 20080277350).

8. Astia, M., De Pietria, G., Rosch, F. et al. Validation of68Ge/68Ga generator processing by chemical purification for routine clinical application of68Ga-DOTATOC. // Nuclear Medicine and Biology. - 2008. - Vol.35. - P.721-724.

9. EN 2343965 C2, 20.01.2009 (WO 2004/089517, EP 1610886).

10. US 7586102 B2, 08.09.2009.

11. WO 2004/089425 A1, 21.10.2004.

12. US 7728310 B2, 01.06.2010.

13. McAlister D.R., E.P. Horwitz Automated two column generator systems for medical radionuclides. Applied Radiation and Isotopes 67 (2009) 1985-1991.

1. The method of obtaining solutions68Ga high purity by successive transmission of the eluate generator68Ge/68Ga through a column of cation exchange resin and the column with anion exchange resin, comprising the following stages: the interaction of the eluate generator68Ge/68Ga with cation exchange resin, which results in the sorption of68Ga, washing the cation exchange resin with the besieged68Ga, elution68Ga with cation exchange resin, the interaction of the obtained eluate from the anion-exchange resin with the besieged68Ga and elution68Ga with anion exchange resin with an aqueous solution of hydrochloric acid, characterized in that for washing the cation exchange resin using a mixture of hydrochloric acid and acetone (volume concentration of hydrochloric acid in the mixture is from 0.2 to 1 m, and the volumetric content of acetone - 20%to 80%) for elution of68Ga with cation exchange resin, a mixture of salt is islote and acetone (volume concentration of hydrochloric acid in the mixture is from 1.8 to 2.5 M, and volumetric content of acetone - from 20 to 79%), in addition, after the deposition of the68Ga on anion-exchange resin rinse anion exchange resin with an organic solvent, with subsequent drainage of air or inert gas, after which elution of68Ga with anion-exchange resin using an aqueous solution of from 0.01 to 0.1 M Hcl, and the volume of it in 15-25 times smaller than the original volume of the eluate generator68Ge/68Ga.

2. The method according to claim 1, where the organic solvent for washing the anion exchange resin using ethyl alcohol.



 

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2 dwg, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: analysed sample is infused with an organic insulating agent. The obtained extract is purified through chromatography on a column of silica gel L 40/100 µ, while performing elution with a mixture of organic solvents. The analysed substance is determined using a chromatographic technique using a mobile phase which contains hexane, dioxane and propanol-2. The organic insulating agent is toluene. The toluene extract is dehydrated with anhydrous sodium sulphate. During the purification process, hexane is first passed through the column and elution is then carried out with a hexane-dioxane-propanol-2 solvent mixture (8:3:0.6 by volume). Eluate fractions containing the analysed substance are merged. The eluent is evaporated. The residue is dissolved in the hexane-dioxane-propanol-2 solvent mixture (15:5:1 by volume) and detection is carried out using high-performance liquid chromatography (HPLC) in a 64×2 mm column filled with Silasorb-600 sorbent using a hexane-dioxane-propanol-2 mobile phase (15:5:1 by volume) and a UV detector.

EFFECT: high accuracy and sensitivity of analysis.

3 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: there is described a method of quantitative cyclosporine A evaluation in patients' blood involving blood protein precipitation by adding an aqueous solution of zinc sulphate and methanol, mixing, centrifuging and sampling a centrifugate; separating the centrifugate ingredients by reverse phase high-yield liquid chromatography, mass-spectrometre detecting cyclosporine A and evaluating the cyclosporine A concentration with plotting a calibration curve; blood protein are precipitated with using whole blood; blood protein precipitation is followed by additional salt impurity precipitation by adding methanol to the centrifugate to the general concentration not less than 90 vol. %, mixing again, centrifuging and sampling the centrifugate; separating the centrifugate ingredients, detecting and evaluating the cyclosporine A concentration.

EFFECT: method allows facilitating analysis simplicity and universality with providing adequate sensitivity and selectivity ensured by the absence of necessity for the internal standard and online extraction and lower requirements to specification of the used mass spectrometre by conducting preliminary impurity precipitation.

1 ex

FIELD: physics.

SUBSTANCE: proposed method comprises forcing analysed product into chromatograph first circuit to define carbon sulphide at its concentration exceeding 0.1 wt % and, at a time, into second circuit at carbon sulphide concentration lower than 0.1 wt %. First circuit comprises piston-type metering valve and packed columns arranged in heated temperature-controlled cabinet and filled with polymer adsorbent, 0.1-1.5 m-long precolumn and 0.5-5 m-long main column, and heat conductivity detector. Second circuit comprises piston-type metering valve, packed capillary columns arranged in heated temperature-controlled cabinet and filled with polymer adsorbent, 0.1-1.5 m-long precolumn and 15-50 m-long main column with their ID making 0.23-0.32 mm, and sulfur-selective detector. Metering valves are arranged sequentially in both circuits along sample feed direction.

EFFECT: shorter easier process.

5 cl, 1 dwg, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying a cyclic or an acyclic peptide selected from a group comprising eptifibatide, exenatide, atosiban and nesiritide or combination thereof, from a mixture containing at least one impurity, involving contacting said mixture with a reverse phase HPLC matrix and an ion-exchange chromatography matrix and obtaining a purified peptide product with purity of at least 96% and, preferably, at least about 99%.

EFFECT: obtaining a purified peptide product.

11 cl, 4 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying a cyclic or an acyclic peptide selected from a group comprising eptifibatide, exenatide, atosiban and nesiritide or combination thereof, from a mixture containing at least one impurity, involving contacting said mixture with a reverse phase HPLC matrix and an ion-exchange chromatography matrix and obtaining a purified peptide product with purity of at least 96% and, preferably, at least about 99%.

EFFECT: obtaining a purified peptide product.

11 cl, 4 tbl, 18 ex

FIELD: process engineering.

SUBSTANCE: invention may be used in hydrometallurgy. Proposed invention allows separating such metals as uranium, nickel, copper and cobalt present in liquid wastes of ore leaching. Solution containing metal ions is forced through stationary layer of resin, Particularly, through, at least, three zones. Note here that solution drive appliances are arranged between adjacent zones and between last and first zones. Proposed method comprises several sequences, each comprising, at least, one step selected from steps of adsorption, washing and desorption. Every next sequence is performed by shifting fronts into zones downstream of circuit with identical increment unless cyclic shift of inlet and discharge points.

EFFECT: optimised amounts of components, higher efficiency.

15 cl, 13 dwg, 2 ex

FIELD: process engineering.

SUBSTANCE: invention may be used in hydrometallurgy. Proposed invention allows separating such metals as uranium, nickel, copper and cobalt present in liquid wastes of ore leaching. Solution containing metal ions is forced through stationary layer of resin, Particularly, through, at least, three zones. Note here that solution drive appliances are arranged between adjacent zones and between last and first zones. Proposed method comprises several sequences, each comprising, at least, one step selected from steps of adsorption, washing and desorption. Every next sequence is performed by shifting fronts into zones downstream of circuit with identical increment unless cyclic shift of inlet and discharge points.

EFFECT: optimised amounts of components, higher efficiency.

15 cl, 13 dwg, 2 ex

FIELD: food industry.

SUBSTANCE: invention relates to a method for purification of defatted milk contaminated with copper, lead and zinc in a concentration from 0.13, 0.23 and 0.34 of MAC respectively. According to the method, one introduces into defatted milk with residual fat content equal to 0.10-0.20% a sorbent preliminarily hydrated with distilled water which sorbent may be represented by alumina oxide powder, broken rice or licorice roots extraction residue, the weight ratio of milk to the sorbents being 25:1. Then one proceeds with maintenance during 20-30 minutes at a temperature of 50-55°C and the sorbent removal by centrifugal method in a milk purifier separator.

EFFECT: invention allows to reduce concentration of copper, lead and zinc and bacterial population in milk and to produce a product of better quality.

1 tbl, 1 ex

FIELD: process engineering.

SUBSTANCE: invention may be used in chemical industry for chromatographic separation of, at least, one normal paraffin, olefin or aromatic hydrocarbon from the mix. SMB separator comprises column, layers of adsorbents Ai-1, … Ai+4 separated by plates Pi-1, … Pi+4 arranged there under, circuits of distribution and extraction of raw material F, desorbent D, raffinate R and extract E, and two-way valves Vi-1…Vi+4 to distribute said fluids. Said column is divided into multiple sections with two or three plates arranged one above the other. Every said section comprises outer bypass line Lk, … Lk+2 communicated with every plate via branch pipe accommodating said two-way valve.

EFFECT: higher efficiency and reliability, simplified design.

21 cl, 9 dwg

FIELD: process engineering.

SUBSTANCE: invention may be used in chemical industry for chromatographic separation of, at least, one normal paraffin, olefin or aromatic hydrocarbon from the mix. SMB separator comprises column, layers of adsorbents Ai-1, … Ai+4 separated by plates Pi-1, … Pi+4 arranged there under, circuits of distribution and extraction of raw material F, desorbent D, raffinate R and extract E, and two-way valves Vi-1…Vi+4 to distribute said fluids. Said column is divided into multiple sections with two or three plates arranged one above the other. Every said section comprises outer bypass line Lk, … Lk+2 communicated with every plate via branch pipe accommodating said two-way valve.

EFFECT: higher efficiency and reliability, simplified design.

21 cl, 9 dwg

FIELD: chemistry.

SUBSTANCE: method involves passing a solution of lipopolysaccharide Shigella flexneri 2a in a 0.05 M triethylammonium acetate buffer at pH 4.7, which contains 10% n-propanol, through a column with a hydrophobic carrier which is Octyl Sepharose CL-4B, and then washing the column with the same buffer solution.

EFFECT: method can be used to produce carriers which enable extraction and purification of specific antibodies to lipopolysaccharides using affinity chromatography.

1 ex

FIELD: medicine.

SUBSTANCE: method involves specific immobilisation of fragments of the specified bacteria from a solution on an affine surface consisting of a protein G layer coated with a layer of antibodies specific to the identified bacterial cells. Two-stage washing of a sample from a non-specifically bound material implies washing in a buffer pH 8.5-9.5 and washing in deionised water. The atomic-force microscopy is used as a visualisation tool of the bound bacterial fragments and enables direct count of a bound analyte amount per a surface unit.

EFFECT: offered invention allows identifying the minute cell concentration in the analysed solution.

1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying alkyl aromatic compounds with an alkyl chain comprising 9-25 carbon atoms, involving the following steps: i) separation of a mixture of alkyl aromatic compounds in a fractionation column, which separates 60-85 wt % of the starting material through the top part the column to obtain a light fraction and a heavy fraction, ii) separation of the heavy fraction from step (i) in a fractionation column which works at pressure in the top part between 0 and 0.1 MPa (0-1 bar), at temperature in the bottom part between 175 and 290°C and temperature in the top part between 90 and 200°C, to obtain a light fraction and a heavy fraction, iii) removing chromophore precursors from the light fraction from step (ii) via percolation filtration through a fixed layer used to clean solid substance, iv) removing light by-products obtained at step (iii) using a distillation column which works at temperature between 60 and 250°C, v) mixing the purified alkylate obtained at step (iv) with a light fraction obtained during distillation at step (i).

EFFECT: use of the present method enables to obtain detergents with low colour grade owing to sulphonation.

16 cl, 2 ex, 6 tbl, 6 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing radioactive technetium-99m labelled nanocolloid. The method is characterised by adding a technetium-99m eluate to an aqueous suspension prepared from nanosized gamma-aluminium oxide powder with particle size of 7-10 nm and concentration of 0.5-0.7 mg/ml after bringing the pH of the medium to 4-5, followed by successive addition of ascorbic acid, tin (II) chloride dihydrate and gelatine in defined amounts. The obtained mixture is heated in a water bath at temperature 70-80°C for 30 minutes, cooled to room temperature in an ultrasonic bath and then subjected to sterilisation filtration.

EFFECT: invention enables to obtain 99mTc-Al2O3 nanocolloid, used based on its size to conduct diagnostic research for which not less than 80% of the particles have size in the range of 20-100 nm, and the radiochemical purity of the preparation is higher than 90%.

1 dwg, 2 tbl, 3 ex

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