Injectable form of 5α androstane-3β,5,6β-triol and method for preparing it

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents an injectable form of 5α-androstane-3β,5,6β-triol containing a liquid injectable form, containing a solvent, or a solid injectable form containing at least one soluble additive with the above at least one soluble additive containing hydroxypropyl-β-cyclodextrine.

EFFECT: invention provides preparing the stable injectable form of 5α-androstane-3β,5,6β-triol.

10 cl, 7 ex, 4 tbl

 

The technical FIELD

The present invention is an invention in the field of pharmaceutical industry and relates to the injectable form 5α-androstane-3β,5,6 β-triol and the way it was received.

The LEVEL of TECHNOLOGY

5α-androstane-3β,5,6 β-triol (hereinafter - YC-6) is a newly open neuroprotective compound. Currently, acute ischemic stroke (OII) mainly treated with thrombolytic or neuroprotective therapy. Neuroprotective agents can reduce the area of cerebral infarction and prevent hemorrhagic complications that may arise during thrombolytic or anticoagulant therapy. In addition, this compound can be applied even in the absence of any etiological diagnosis, which allows for early treatment. Therefore, neuroprotective agents has received increasing attention in the study of OII.

However, to date, neuroprotective agents with proven safety and efficacy are not available. A large number of compounds that have potential value for clinical use, are at the stage of clinical trials, including calcium channel blockers (CCBS), calcium channel modulators, inhibitors of the release of glutamate, agonists of the receptors, γ-aminobutyric acid (GABA), the trap was free radical is, antibodies to factors intercellular adhesion and so on.

Among the large number of connections become more attractive neuroactive steroids due to their wide range of actions in relation to the protection of neurons. In particular, the recently opened neuroprotective chemical compound YC-6 is not limited to the protection of neurons. This connection effectively not only against cerebral ischemia, but also against spinal cord ischemia during daily dose of 50-100 mg

YC-6 insoluble in water. Although its solubility increases in traditional non-aqueous solvents or mixtures of these solvents cause irritation, and when diluted with water, YC-6 may precipitate. This adversely affects the efficiency and safety injection YC-6 and limits the possibility of their application.

BRIEF description of the INVENTION

To overcome the shortcomings discussed above, according to the present invention proposed injectable form YC-6 and the methods for their preparation. According to the present invention is used hydroxypropyl-β-cyclodextrin as solubilizing agent for the preparation of injectable YC-6. The irritation caused by non-aqueous solvents, successfully reduced while increasing the solubility of YC-6.

To achieve this, the proposed injectable form Y-6 in liquid or solid form. Injectable forms contain at least one soluble excipient, including hydroxypropyl-β-cyclodextrin. The specified at least one soluble excipient may also contain an agent that regulates isotonicity, or filler for freeze-drying.

Preferably, YC-6 is present in a mass ratio of 1~20:40~500 to hydroxypropyl-β-cyclodextrin.

Injectable form can also be obtained using the following components (by weight): 1~20 parts of YC-6, 40~500 parts of hydroxypropyl-β-cyclodextrin, 1~100 parts agent, governing isotonicity, 0~200 parts of filler for freeze-drying and 0~2000 parts of solvent.

The agent governing isotonicity selected from the group consisting of sodium chloride, glucose, mannitol, lactose, xylitol, sorbitol, maldita and mixtures thereof.

Filler for freeze drying is selected from the group consisting of sodium chloride, glucose, mannitol, lactose, xylitol, sorbitol, maldita and mixtures thereof.

To prepare a liquid injectable form a solvent selected from the group consisting of propane diol, ethanol, polyethylene glycol 400, polyethylene glycol 200, glycerin, water and mixtures thereof.

The injectable form according to the present invention can be obtained by a process comprising a stage that posledovatel is but dissolved in water for injection hydroxypropyl-β-cyclodextrin, YC-6 and at least one soluble excipient to obtain the original solution; then the specified source solution successively subjected to bleaching, filtration and sterilization of obtaining injectable form according to the present invention.

Lyophilized powder obtained by filling the ampoule with a filtrate obtained at the stage of filtration above, and freeze drying.

Sterile powder is obtained by spray drying of the filtrate obtained at the stage of filtration above, with the subsequent packing.

Bleaching may be carried out using a 0.1~0.3% of activated charcoal, and sterilization can be carried out at a temperature of 115°C for 30 minutes or at 121°C for 15 minutes

It should be noted that YC-6 can also be prepared in the form of YC-6 for infusion by mixing injectable form YC-6 with traditional perfusions without medicines, such as glucose for infusion, sodium chloride solution for infusion or glucose and sodium chloride for infusion.

The present invention provides advantages in comparison with traditional methods. The use of hydroxypropyl-β-cyclodextrin or non-aqueous solvents and mixed solvent increases the solubility of YC-6 so that YC-6 can be obtained in the form of a solution for which Nyenzi, sterile powder, lyophilized powder, YC-6 for infusion on the basis of glucose, sodium chloride or glucose and sodium chloride, which provides the possibility of intravenous YC-6 if necessary. In addition, when cooking in injectable form according to the present invention YC-6 has a sufficient solubility and efficacy without causing irritation. The process of obtaining simple and widely available.

DETAILED description of the INVENTION

Example 1. Getting 200 ampoules of injectable form of YC-6 (specification 5 ml: 50 mg)

Composition:

YC-610 g
2-Hydroxypropyl-β-cyclodextrin200 g
Sodium chloride1,25 g
Water for injection to1000 ml

Preparation of: 2-hydroxypropyl-β-cyclodextrin dissolved in 80% freshly prepared water for injection and add YC-6, then stirred at room temperature for 10~20 minutes until complete dissolution of YC-6. Add sodium chloride and dissolve it by stirring, then add water for injection to volume of 1000 ml. of the above solution add 0.1% of activated charcoal lane is mesilat for 15 min at 60°C, and then cool the solution is naturally to room temperature. For filtering applied 0.22 μm microporous membrane filter. The filtrate is collected and poured with getting 5 ml injectable form, then sterilized at 121°C for 15 minutes

Example 2. Getting 200 vials YC-6 injection (specification 10 ml: 80 mg)

Composition:

YC-616 g
2-Hydroxypropyl-β-cyclodextrin400 g
Glucose13,9 g
Water for injection to2000 ml

Preparation of: 2-hydroxypropyl-β-cyclodextrin dissolved in 80% freshly prepared water for injection and add YC-6, then stirred at room temperature for 10~20 minutes until complete dissolution of YC-6. Add glucose and dissolve it by stirring, then add water for injection to volume to 2000 ml of the above solution add 0.1% of activated carbon, stirred for 15 min at 60°C and then cooled solution naturally to room temperature. For filtering applied 0.22 μm microporous membrane filter. The filtrate is collected and poured with 10 ml injectio the Noi form, then sterilized at 121°C for 15 minutes

Example 3. Getting 200 vials YC-6 injection (specification 5 ml: 100 mg)

Composition:

YC-620 g
2-Hydroxypropyl-β-cyclodextrin400 g
Water for injection to1000 ml

Preparation of: 2-hydroxypropyl-β-cyclodextrin dissolved in 80% freshly prepared water for injection and add YC-6, then stirred at room temperature for 10~20 minutes until complete dissolution of YC-6. Add water for injection to volume of 1000 ml. of the above solution add 0.1% of activated carbon, stirred for 15 min at 60°C and then cooled solution naturally to room temperature. For filtering applied 0.22 μm microporous membrane filter. The filtrate is collected and poured with getting 5 ml injectable form, then sterilized at 115°C for 30 minutes

Example 4. Getting 200 sterile powder YC-6 (specification 80 mg/vial)

Composition:

YC-616 g
2-Hydroxypropyl-β-cyclodextrin 400 g
Sodium chloride2.5 g
Packing200 vials

Preparation of: 2-hydroxypropyl-β-cyclodextrin dissolved in 80% freshly prepared water for injection and add YC-6, then stirred at room temperature for 10~20 minutes until complete dissolution of YC-6. Add sodium chloride and dissolve it by stirring, then add water for injection to volume 2000 ml of the above solution add 0.1% of activated carbon, stirred for 15 min at 60°C and then cooled solution naturally to room temperature. For filtering applied 0.22 μm microporous membrane filter. The filtrate is dried by spray drying and then Packed in 200 vials.

Example 5. Getting 200 vials of lyophilized powder YC-6 (specification 5 ml: 60 mg)

Composition:

YC-612 g
2-Hydroxypropyl-β-cyclodextrin200 g
Glucose7 g
Water for injection to1000 ml

Preparation of: 2-hydroxypropyl-β-C is CODEXTER dissolved in 80% freshly prepared water for injection and add YC-6, then stirred at room temperature for 10~20 minutes until complete dissolution of YC-6. Add glucose and dissolve it by stirring, then add water for injection to volume to 1000 ml of the above solution add 0.1% of activated carbon, stirred for 15 min at 60°C and then cooled solution naturally to room temperature. For filtering applied 0.22 μm microporous membrane filter. The filtrate is poured into 5 ml ampoules and then freeze-dried.

Example 6. Joint stability injectable form YC-6 and generally accepted solutions for infusion.

Two ampoules of injectable form of YC-6 (5 ml X 2) from example 1 is added in the conventional solution for infusion to assess joint stability YC-6 within 8 hours. Indicators to assess joint stability include color, transparency, pH and content of YC-6. The results are presented in the following tables.

Table 1
Compatibility tests injectable form YC-6 and generally accepted solutions for infusion
DesignationCompatibility tests (25-30°C)
AInjectable form of YC-6 5 2 MLH+5% glucose solution for injection 250 ml
BInjectable form of YC-6 5 ml X 2+0.9% sodium chloride for injection 250 ml
CInjectable form of YC-6 5 ml X 2+glucose and NaCl for injection 250 ml
DInjectable form of YC-6 5 ml X 2+composition with NaCl for injection 500 ml
EInjectable form of YC-6 5 ml X 2+5% solution of sodium bicarbonate for injection 250 ml

Table 2
Changes in color and transparency of the conventional solutions for infusion
DesignationBefore adding theAfter adding (h)
0248
AndColorless,Colorless,Colorless,Colorless,Colorless,
transparent transparenttransparenttransparenttransparent
InColorless,Colorless,Colorless,Colorless,Colorless,
transparenttransparenttransparenttransparenttransparent
Colorless,Colorless,Colorless,Colorless,Colorless,
transparenttransparenttransparenttransparenttransparent
DColorless,Colorless,Colorless,Colorless,Colorless,
transparenttransparent transparenttransparenttransparent
EColorless,Colorless,Colorless,Colorless,Colorless,
transparenttransparenttransparenttransparenttransparent

Table 3
The change in pH in the conventional solutions for infusion
DesignationBefore adding theAfter adding (h)
0248
And4,054,064,05as 4.024,08
Inthe ceiling of 5.605,625,5 5,465,58
as 4.024,044,034,004,04
D5,645,62the ceiling of 5.605,595,59
E7,997,94of 7.908,048,00

Table 4
Changes in the concentration of YC-6 traditional solutions for infusion
Designation0 h2 hours8 h24 hours
And375,4364,7367,7363,4
Into 379.2373,5380,4386,1
385,6387,6383,4384,5
D382,0383,7387,2380,8
E386,7375,1381,3376,5

Example 7. Preliminary safety assessment of YC-6

The Kunming mice were placed in a cage by weight and randomly divided into 5 groups. Each group consisted of 10 mice, half male and half female. Injectable form YC-6, obtained according to example 3 (20 mg/ml)was injected intravenously into the tail vein at various doses. All mice were killed after one week of observation. Toxic reaction and the number of dead animals were recorded every day. Expected LD50and 95% confidence interval. LD50YC-6 amounted to more than 400±121 mg/kg

Blood cells were obtained according to standard methods from fresh blood obtained from new Zealand rabbits. Blood cells were diluted with saline to obtain a 2% suspension. Injectable form YC-6, obtained according to example 1 was then added to 2% suspension, and incubated at 37°C during the 3 hours. The coefficient of hemolysis was determined by the colorimetric method. The coefficient of hemolysis YC-6 for injection was less than 1%.

Guinea pigs-albinos were subjected to anaphylactic tests in accordance with conventional methods. Anaphylactic reactions after intravenous injection of the form YC-6, obtained according to example 1, was not observed.

New Zealand rabbits were used to test for irritation of blood vessels when administered intravenously injectable form YC-6, obtained according to example 1. The results showed that tissue changes marginal ear vein in the test group and the control group are similar. Each rabbit whole blood vessels marginal ear vein and normal structure of the veins. Any pathological changes, such as the damage of endothelial cells or swelling of surrounding tissue was not observed.

1. The injectable form 5α-androstane-3β,5,6 β-triol, including liquid injectable form containing solvent or solid injectable form containing at least one soluble excipient, and the specified at least one soluble excipient comprises hydroxypropyl-β-cyclodextrin.

2. The injectable form under item 1, characterized in that the 5α-androstane-3β,5,6 β-triol is present in a mass ratio of 1~20:40~500 to hydroxyprop the Il-β-cyclodextrin.

3. The injectable form under item 1 or 2, characterized in that the soluble excipient further comprises an agent that regulates isotonicity, and/or a filler for freeze-drying.

4. The injectable form under item 3, characterized in that the agent regulating isotonicity selected from the group consisting of sodium chloride, glucose, mannitol, lactose, xylitol, sorbitol, maldita and mixtures thereof.

5. The injectable form under item 3, characterized in that the filler for the freeze drying process selected from the group consisting of sodium chloride, glucose, mannitol, lactose, xylitol, sorbitol, maldita and mixtures thereof.

6. The injectable form under item 1 or 2, characterized in that the solvent for liquid injectable form selected from the group consisting of propane diol, ethanol, polyethylene glycol 400, polyethylene glycol 200, glycerin, water and mixtures thereof.

7. The injectable form under item 3, characterized in that the injection form consists of (by weight): 1~20 parts 5α-androstane-3β,5,6 β-triol, 4~500 parts of hydroxypropyl-β-cyclodextrin, 1~100 parts agent, governing isotonicity, 0~200 parts of filler for freeze-drying and 0~2000 parts of solvent.

8. The method of obtaining injectable form under item 1, which includes stages, according to which:
(a) sequentially dissolving hydroxypropyl-β-cyclodextrin, 5α-androstane-3β,5,6 β-Tr the ol and additional soluble excipients in water for injection to obtain an initial solution for injection and
(b1) the specified source solution for injection is subjected to bleaching, depyrogenation, filtration and sterilization with obtaining the specified injectable form, or
(b2) the specified source solution for injection is subjected to bleaching, depyrogenation, filtering, and the location of the obtained filtrate in ampoules with subsequent freeze-drying to obtain lyophilized powder, or
(b3) the specified source solution for injection is subjected to bleaching, depyrogenation, filtration and spray drying of the filtrate followed by packaging.

9. The method according to p. 8, characterized in that the discoloration provide through the use of activated carbon in the amount of 0.05~0.3 wt.% from mass injectable form.

10. The method according to p. 8 or 9, characterized in that the sterilization is carried out at 115°C for 30 minutes or at 121°C for 15 minutes.



 

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SUBSTANCE: invention refers to a compound of formula

,

wherein: each of R1, R2, R4, R5, R6, R7, R8 R9, R10, R11, R12, R13, R14, R15 R16 and R17 is independently specified in a group consisting of deuterium or hydrogen; and R3 is independently specified in a group consisting of CD3 and CH3; provided R3 represents CH3, at least one of the groups R1, R2, R4, R5, R6, R7, R8 R9, R10, R11, R12, R13, R14, R15 R16 and R17 represents deuterium; and R18 represents hydrogen. The invention also refers to a drug on the basis of the above compound for treating a condition causing pain.

EFFECT: there are prepared new compounds inhibiting MMPs (metalloproteinases) which show the high activity, metabolic stability and/or lower toxicity in relation to the currently known MMP inhibitors for treating pain and other diseases, such as cancer.

16 cl, 2 dwg, 14 tbl, 136 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: storage-stable pharmaceutical composition represents a liquid formulation containing bortezomib and a system of anhydrous solvents and applicable for injection. A primary ingredient of the system of anhydrous solvents is propylene glycol. Bortezomib is found in the concentration of at least 1 mg/ml. The pharmaceutical composition contains a total amount of aqueous buffer of 10 vol. % or more.

EFFECT: stable pharmaceutical composition according to invention maintains bortezomib degradation at the level of not less than 10 wt % when keeping the liquid formulation for at least three months in the ambient environment.

9 cl, 10 tbl

FIELD: medicine.

SUBSTANCE: microspheres contain diclofenac in the form of an acid included in a matrix of a biodegradable polymer specified in a group consisting of polylactide and polylactide-co-glycolide; an average size of microspheres falls within the range of 5 to 150 mcm; a degree of diclofenac inclusion makes 5-50%, and the said microspheres release 60 to 95% diclofenac for 14 days.

EFFECT: extended range of methods for preparing injectable agents for treating inflammatory conditions, such as rheumatoid arthritis, osteoarthritis and rheumatoid spondylitis characterised by the prolonged diclofenac release.

4 cl, 3 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to methods of obtaining a lyophilised preparation of tetrodotoxin and to a tetrodotoxin preparation for relief of the drug withdrawal in case of addiction to opiates. The method of obtaining the lyophilised preparation of tetrodoxin includes the following stages: 0.1-20 mcg/dose of tetrodotoxin is dissolved with 0.1% solution of citric acid to regulate pH within the range of 3.5-4.5 in injection water and filtered to remove pyrogen; separately dissolved are: a stabiliser - dextran or trehalose - and a filling agent, representing an isotonic solution of sodium chloride or mannit in injection water. After that, 0.1% solution of citric acid is added to regulate pH within 3.5-4.5, then, activated carbon is added with keeping at a temperature of 60°C and mixing for more than 30 minutes, filtering to remove pyrogen and cooling to room temperature. After homogeneous mixing of the obtained solutions and realisation of ultrafiltration, lyophilic drying is carried out. Lyophilic drying consists in preliminary freezing, drying under vacuum at reduced temperature, drying under vacuum at increased temperature, with each drying being performed at a certain temperature for the specified time period. After that, filling with inert gas is performed with control of water content at 3% level, with further sealing. Another version includes addition of additional solution of lidocaine chloride to the solution of tetrodotoxin and citric acid at the first stage. Also disclosed is the tetrodotoxin preparation for relief of the drug withdrawal in case of addiction to opiates, obtained by the said method, which is characterised by the weight ratio tetrodotoxin:filling agent:stabiliser, equal to 1:(150-3000):(50-6000).

EFFECT: claimed group of inventions ensures obtaining the stable tetrodotoxin solution with accurate dosage, which is used for introduction into the human organism.

25 cl, 9 tbl, 14 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, namely to pharmacology and describes a histidine-free pharmaceutical composition containing high-purity factor VIII; arginine and saccharose, a surfactant for the prevention or at least the inhibition of a surface adsorption of factor VIII; 0.5 to 10 mM calcium chloride for the specific stabilisation of factor VIII, and sodium citrate or maleic acid as a pH buffer.

EFFECT: invention provides the protective function for preserve high-yield factor VIII over the whole cycle of pharmaceutical processing, long storage and end recovery and administration into the patient.

18 cl, 16 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to traumatology and orthopaedics, enabling preparing a biologically active preparation of autoblood for enhancing neogenesis processes. The presented technique involves sampling whole blood, centrifuging, selecting a middle layer of plasma so that to avoid the erythrocyte ingress. The centrifuged platelet concentrate is frozen in a cold room at temperature below minus 1 C°, dried for at least three minutes within the temperature range of 2 C° to 52 C°; the lyophilisate is sterilised before use.

EFFECT: technique of platelet-rich plasma lyophilisation enables preserving the TGF PDGF VEGF factor viability min 1,5 months from the moment of blood sampling.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacology, pharmaceutics and medicine, more specifically to a new generation of high-stable dosage forms prepared with using the process of sublimation in a specific mode with a composition containing no stabilising agents reducing the width of therapeutic action of finished dosage form substantially. The invention concerns the pharmaceutical composition for injections and infusions containing 3-oxy- and methylpyridine derivatives and pharmaceutically acceptable salts thereof as an active ingredient, sodium chloride or potassium chloride as an additive agent, in the form a lyophilisate. The process involves the sublimation followed by the vacuum dewatering for at least 64 hours.

EFFECT: pharmaceutical composition possesses high stability for the whole shelf-life as opposed to all known pharmaceutical formulations of these compounds; it preserves pharmacological activity and enables dissolving the composition immediately before use and reducing a risk of the negative effect of the thermal sterilisation of aqueous solutions.

2 cl, 7 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine. A pharmaceutical formulation for the treating diseases associated with endothelial dysfunction contains an active ingredient presented by a methyl pyridine derivative - 1.0-6.0 wt %; purine - 10.0-80.0 wt % and additive agents - the rest. The active substance is presented by compounds of a group: 3 -(N,N-dimethyl carbamoyloxy)-2-ethyl-6-methylpyridinium succinate, 3-methylpyridinium succinate, 2-ethyl-6-methyl-3-hydroxypyridinium hydrochloride, 6-trichloromethyl-2-chloropyridine (nitrapyrin), 2-ethyl-6-methyl-3-hydroxypyridine succinate. Purine is presented by inosine, adenosine, hypoxanthine. The pharmaceutical formulation may be presented in the form of injections, lyophilisate, solid capsules, tablets and suppositories.

EFFECT: formulation according to the invention provides creating the stable drug dosage form which considerably exceeds the existing analogues in pharmacodynamics activity on the endothelial dysfunction and toxicological properties.

4 cl, 4 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for preparing fine pharmaceutical compositions of salbutamol. The declared method consists in quick cooling of an initial solution of salbutamol and glycine or salbutamol and lactose monohydrate in a solvent of tetrahydrofuran (THF) and water, wherein the THF concentration makes 5-25 wt % by spraying the initial solution into a container with liquid nitrogen. The prepared mixture of solid phases is cleaned from the solvents by sublimation in a liquid nitrogen flow with continued pumping by progressive temperature increase: -196°C to -5°C with pressure decrease 100 Pa to less than 2 Pa, then to +30°C, and kept for 2 hours at specified temperature and pressure increase to 1 atm. The salbutamol concentration in the initial solution makes 4 wt % per weight of the solvent of THF and water, while the glycine and lactose monohydrate concentration makes up to 10 wt % per weight of the solvent of THF and water.

EFFECT: invention provides preparing the fine pharmaceutical compositions of salbutamol characterised by bulk density of 0,3-0,45 g/cm3 and high surface unit area, applicable in inhalation therapy.

19 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to immunology, and concerns preparing meningococcal vaccines. What is presented is a kit for preparing an immunogenic composition for serogroup B Neisseria meningitidis containing: (i) a first containing comprising an adjuvant containing an oil-in-water emulsion; and (ii) a second containing comprising a lyophilised antigenic composition containing an immunogen for inducing the immune response to serotype B Neisseria meningitidis. The lyophilized antigens Men-B may be reduced into an adjuvant form ready for administration into the patient at the moment of use. The lyophilised component may also contain one or more conjugated saccharides of serogroup A, C, W135 and/or Y N. meningitides.

EFFECT: invention enables preparing the storage-stable and effective compositions.

7 cl, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and pharmaceutics, and concerns a stable isotonic active composition containing protein in the amount of min. 50 mg/ml and a solvent which is used to dissolve the composition prepared of a lyophilised mixture of protein and a lyoprotectant, wherein the molar ratio of the lyoprotectant and protein in the mixture makes 100-600 moles of the lyoprotectant per 1 mole of the protein with the protein concentration in the dissolved active composition is 2-40 times higher than the protein concentration in the mixture before lyophilisation. What is also declared is a composition containing an antibody, particularly an anti-lgE-antibody or an anti-HER2-antibody, and a drug for treating mammals with some disorders characterised by HER2-receptor overexpression, particularly for treating cancer. The methods for preparing the composition involve the stages of lyophilisation of the mixture of the protein and lyoprotectant which is succhrose or trehaloes, dissolving the lyophilised mixture with a solvent to the protein concentration of min. 50 mg/ml.

EFFECT: group of inventions provides preparing the active composition stable at the high concentrations of the protein.

42 cl, 2 ex, 10 tbl, 19 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the chemical-pharmaceutical industry and represents a carrier for chewing gum in the form of particles for the controlled release of an active ingredient (ingredients), absorbed in the said carrier and/or adsorbed on it, characterised by the fact, that the said carrier contains 0.1-50 mcm of a calcium carbonate particle, preliminarily processed with an acid, selected from the group, which consists of H2SO4, HSO4-, H3PO4, oxalic acid and their mixtures, and gaseous CO2, and the specific area of surface of BET particles of calcium carbonate is increased to the level more than 15 m2/g according to the standard method of measuring the specific area of BET surface.

EFFECT: obtaining the carrier for chewing gum.

6 cl, 10 ex

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