Agent for enhancing corneal epithelial barrier function

FIELD: medicine.

SUBSTANCE: group of inventions refers to ophthalmology. The group of inventions refers to pharmacological action of a compound functioning as a PPARr agonist on the corneal epithelial barrier function. The PPARr agonist, such as rivoglitazone, DRF-2593, GW-544 and BMS-298585, perfectly enhances the corneal epithelial barrier function in the study of enhancing the corneal epithelial barrier function, and therefore it is useful as a preventive agent or therapeutic agent for an ocular infection or eye complaints of unknown aetiology caused by the decreased corneal epithelial barrier function.

EFFECT: group of inventions provides enhancing the corneal epithelial barrier function in the patients with diabetes, age-related decrease in the corneal epithelial barrier function, and patients underwent refractive surgery, such as PRK (photorefractive keratectomy) and LASIK (laser keratomileusis in situ), and cataract surgery.

12 cl, 2 tbl, 4 ex

 

The technical field

The invention relates to an agent for strengthening the barrier function of the corneal epithelium, including PPARγ agonist as an active ingredient.

Background of the invention

The cornea is a transparent avascular tissue with a diameter of approximately 1 cm and a thickness of approximately 1 mm, formed by the epithelium and the stroma of the cornea and, as you know, has a greater effect on visual function.

As one of the important functions of the corneal epithelium may be mentioned the formation of a barrier between the environment and corneal stroma of the cornea. This barrier function of the corneal epithelium is primarily intended to regulate the penetration of the substances present in the tear fluid, and pathogens, such as bacteria and fungi, from the epithelium into the stroma of the cornea. It was published that the barrier function of the corneal epithelium is suppressed in patients with diabetes, and decreases with age (non-patent documents 1, 2 and 3). I think that with the decrease of the barrier function of the various substances present on the surface of the eye, randomly penetrate the cornea and then stimulate the sensitive nerves of the cornea. This stimulation becomes a factor in ocular discomfort.

It was also published that in the case of refractive surgery such as PRK (photorefractive keratectomy) and LASIK (lasermicronics in situ), and cataract surgery barrier function of the corneal epithelium is reduced after surgery, and eyes penetrate various pathogens that can cause infectious diseases (non-patent documents 4 and 5). In addition it is also known that in the fall of the barrier function of the corneal epithelium is disrupted interaction between the epithelium of the cornea and lacrimal fluid, leading to a reduction in the functional visual acuity.

It is known that PPARγ-preserving spread in energy of the organs, such as adipose tissue, and has effects on the differentiation and proliferation of adipocytes. As PPARγ agonists are known compounds having thiazolidindiones skeleton, such as 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone) and 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), and compounds that do not have thiazolidindiones skeleton, such as N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544) and N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585).

It was published that the PPARγ agonist improves insulinorezistentne dia is et and effective as a therapeutic agent for diseases, related to insulin resistance such as diabetes mellitus and hyperglycemia, as well as inflammatory diseases such as osteoarthritis and rheumatoid arthritis (patent document 1). In addition it was also published that the PPARγ agonist was effective as a therapeutic agent for diseases of the conjunctiva and cornea, such as dry eyes, corneal ulcer, keratitis and conjunctivitis (patent documents 2, 3 and 4).

However, no data was published about the study-improving effect of the above-mentioned connections on the barrier function of the corneal epithelium. The study of the pharmacological effect of the compounds functioning as a PPARγ agonist, on the barrier function of the corneal epithelium is a very interesting task.

Patent document 1: Patent publication Japan No. 2976885

Patent document 2: Publication of the patent application of Japan No. 2005-145961

Patent document 3: Publication of the patent application of Japan No. 2005-162735

Patent document 4: Publication of the patent application of Japan No. 2005-350451

Non-patent document 1: The Cornea. Scientific Foundations and Clinical Practice. Third Edition. (1994) 25-46

Non-patent document 2: Cornea 1993; 12(6): 493-499

Non-patent document 3: Cornea 2004; 23(1): 35-37

Non-patent document 4: Journal of Refractive Surgery 1999; 15 (suppl 2): S221-S224

Non-patent document 5: International Ophthalmology 1995-1996; 19(): 225-233

Description of the invention

To study the involvement of PPARγ agonist in the barrier function of the epithelium of the retina, the inventors conducted a study on strengthening the barrier function of the epithelium of the retina using compounds that function as agonists of PPARγ. In the result, the inventors have found that these compounds markedly increased barrier function of the epithelium of the retina, and thereby completed the present invention.

Accordingly, the present invention is directed to:

(1) an agent for strengthening the barrier function of the corneal epithelium, which includes the PPARγ agonist as an active ingredient,

(2) a prophylactic or therapeutic agent against eye infections associated with a decrease in the barrier function of the epithelium of the retina, which includes the PPARγ agonist as an active ingredient,

(3) the agent for improving ocular discomfort associated with a decrease in the barrier function of the corneal epithelium, which includes the PPARγ agonist as an active ingredient, and

(4) the agent for recovery of functional visual acuity, which includes the PPARγ agonist as an active ingredient.

In the present invention has no specific limitation in respect of the PPARγ agonist, provided that the compound acts as a PPARγ agonist (hereinafter simply referred to as "the present compound"), and it can in order to be a connection, having thiazolidindiones skeleton, or connection that does not have thiazolidindiones skeleton. Examples of compounds having thiazolidindiones skeleton, include 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone) and 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), and examples of compounds that do not have thiazolidindiones skeleton, include N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544)N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585), E-4-[4-(5-methyl-2-phenyl-4-oxazolidinone)benzylamino]-4-phenylalanyl acid (TAK-559), Z-2-[4-(5-methyl-2-phenyl-4-oxazolidinone)benzylamino]-2-(4-phenoxyphenyl)-acetic acid (TAK-664), 2-[2-propyl-3-[3-[2-ethyl-4-(4-forfinal)-5-hydroxyphenoxy]propoxy]phenoxy]benzoic acid (LY-293111), 2(S)-methoxy-3-[4-[3-(4-phenoxyphenoxy)propoxy]phenyl]propionic acid (LY-519818), (-)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid 2-(acetylamino)ethyl ester (MBX-102) and (-)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid.

In relation to the salts of the above compounds, there are no restrictions, provided th is it is pharmaceutically compatible, and the examples include a salt with an inorganic acid, such as hydrochloric acid, nitric acid and sulfuric acid; salts with organic acid, such as acetic acid, fumaric acid, maleic acid, succinic acid and tartaric acid; and a salt with alkali metal or alkaline earth metal such as sodium, potassium and calcium. The preferred salt is a salt of hydrochloric acid. In the present invention in Sol also includes Quaternary ammonium salt of this compound. In addition, if there are geometric isomer or an optical isomer of the present compounds, their isomers are also included in the present invention. It should be noted that this connection can be in the form of a hydrate or of MES.

In the present invention, the expression "barrier function of the corneal epithelium" refers to the functions of regulation penetration of substances present in the tear fluid, and penetration of pathogens, such as bacteria and fungi, from the cornea epithelium to the stroma of the cornea. Agent for strengthening the barrier function of the corneal epithelium according to the present invention can enhance the barrier function of the corneal epithelium in patients with diabetes, patients with age-related decrease in the barrier function of the corneal epithelium and the patient, which was held refractive x is rorge, such as PRK (photorefractive keratectomy) and LASIK (laser in situ Keratomileusis), and cataract surgery.

Using the barrier function of the corneal epithelium, for example, it becomes possible prevention or treatment of eye infections caused by the decrease in the barrier function of the corneal epithelium, and the restoration of disturbed interaction between the epithelium of the cornea and lacrimal fluid to prevent functional decline in visual acuity.

Agent for strengthening the barrier function of the corneal epithelium according to the present invention can be administered orally or parenterally. Examples include introduction of eye drops, eye ointment, the form of injections, tablets, capsules, granules and powders, and particularly preferred are eye drops. Their pharmaceutical preparation can be prepared using standard techniques. For example, in the case of eye drops pharmaceutical composition can be prepared using, if desired, an isotonic agent such as sodium chloride and concentrated glycerin, a buffer agent such as sodium phosphate and sodium acetate; surfactants, such as polyoxyethylene-sorbitan monooleate, polyoxyl 40 stearate and utverjdenie a polyoxyethylene castor oil; a stabilizing agent, such as sodium citrate and edetate sodium; and it is of servant, such as benzalkonium chloride and paraben. Regarding pH no restrictions, provided that it is compatible with ophthalmic drug, but it is preferable range 4-8.

In the case of ointments for the eyes it is possible to prepare using conventional bases for ointments, such as white petrolatum and liquid paraffin. In the case of an oral agent, such as a tablet, capsule, granule or powder, if desired, may be added a substance to increase, such as lactose, crystalline cellulose, starch, and vegetable oil; lubricant such as magnesium stearate and talc; a binder such as hydroxypropylcellulose and polyvinylpyrrolidone; disintegrants, such as calcium carboxymethyl cellulose and hypromellose to the low level of substitution; the substance for coating, such as hypromellose, macrogol or silicone resin; and a film forming agent such as gelatin film.

The dosage could be suitably selected depending on symptoms, age, dosage forms and the like, but preferably, in the case of eye drops in the eye buried drop containing of 0.0001-1% (weight/volume), preferably 0.001 to 1% (weight/volume) agent, one or more times a day. In the case of oral agent in General 0.1 to 5000 mg, preferably 1 to 1,000 mg of the agent was administered alone and is several times a day.

As will be described below, the study reinforce the barrier function of the corneal epithelium revealed that the compound of the present invention, functioning as a PPARγ agonist, superb increased barrier function. Accordingly, it becomes possible prevention or treatment of eye infections associated with a decrease in the barrier function of the epithelium of the cornea, improving ocular discomfort associated with a decrease in the barrier function of the corneal epithelium, and the restoration of disturbed interaction between the epithelium of the cornea and lacrimal fluid to prevent functional decline in visual acuity. In addition, the compound of the present invention may enhance the barrier function of the corneal epithelium in patients with diabetes, patients with age-related decline in barrier function of the corneal epithelium and patients after refractive surgery such as PRK (photorefractive keratectomy) and LASIK (laser in situ Keratomileusis), and cataract surgery.

The preferred method of carrying out the invention

The results of pharmacological tests and options for pharmacological preparations described below. They are given for a better understanding of the present invention, but they should not be construed as limiting the scope of the present invention.

[Pharmacological test 1] the Reinforcing effect of the PPARγ agonist on BA is Leroy function

Estimated effect of PPARγ agonist in relation to strengthening the barrier function of epithelial cells of the cornea. As the epithelial cells of the cornea used immortalizing using SV-40 cell line epithelium of the cornea of a person using the electrical resistance of the membrane as an indicator of barrier function. When strengthening the barrier function of the epithelial cells of the cornea increases the electrical resistance of the membrane, whereas the decrease of the barrier function of the electrical resistance of the membrane is reduced.

(The methodology of the experiment)

Immortalitya using SV-40 cell line epithelium of the cornea of the person (NSE-T) was obtained from RIKEN BioResource Center. On cultural liner 24-hole tablet Transwell Clear (Corning Incorporated) were sown 6,h cells, NSE-T, and incubated at 37°C in 5%CO2. As the culture medium used DMEM/Ham's F12 (Nacalai Tesque, Inc.), containing 15% fetal calf serum (ICN) and 40 µg/ ml gentamicin (Gibco). The samples were obtained by removing the culture medium after 9 hours, 2 days, 3 days and 4 days and on replacing the culture medium containing one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]IU is Il]-2,4-thiazolidinedione (pioglitazone) and 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), as a PPARγ agonist with thiazolidinediones skeleton, each at 10 μm, or in culture medium containing one of N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544) and N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) as a PPARγ agonist with nationalidentity skeleton, each at 10 μm. The above-mentioned concentration was obtained by dissolving each sample in DMSO and diluting thousandfold solution in culture medium. In addition, as a basic culture medium used culture medium containing only DMSO.

Five days after seeding of the cells was measured electrical resistance of the layer of epithelial cells, using a system of measurement of electrical resistance of the membrane (World Precision Instruments). As background values measured well, containing only the basic environment without epithelial cells of the cornea, and the obtained value is subtracted from the electrical resistance of the layer of epithelial cells. The resulting value was multiplied by the area of cell culture (0,33 cm2), thereby obtaining the electric resistance (Ω•cm2) per unit area.

(Result)

The electrical resistance of the membrane (average of four experiments) for each sample is provided in table 1.

Table 1
Sample [10 μm]The electrical resistance of the membrane (Ω•cm2)
Rivoglitazone615,9
DRF-2593485,8
Pioglitazone350,3
Rosiglitazone343,2
GW-544435,3
BMS-298585375,1
The basic culture medium296,0

(Discussion)

As can be seen from table 1, all the PPARγ agonists used in this pharmacological test showed a higher electrical resistance relative to the base culture medium. In other words, it was shown that the PPARγ agonist, regardless of the presence thiazolidindiones skeleton strengthens the barrier function of epithelial cells of the cornea. Excellent effect of enhancing the barrier function in particular showed rivoglitazone, DRF-2593, BMS-298585, and GW-544, and a particularly strong effect of strengthening the barrier function showed rivoglitazone.

[Farmak is a logical test 2] the Effect of the PPARγ antagonist effect of strengthening the barrier function of the PPARγ agonist

Assessed the effect of the PPARγ antagonist in the effect of strengthening the barrier function of the PPARγ agonist and evaluated based or no effect of strengthening the barrier function of the activity of PPARγ agonist.

(The methodology of the experiment)

Immortalitya using SV-40 cell line epithelium of the cornea of the person (NSE-T) was obtained from RIKEN BioResource Center. On cultural liner 24-hole tablet Transwell Clear (Corning Incorporated) were sown 6,4x104cells and NSE-T, and incubated at 37°C in 5%CO2. As the culture medium used DMEM/Ham's F12 (Nacalai Tesque, Inc.), containing 15% fetal calf serum (ICN) and 40 µg/ ml gentamicin (Gibco). The samples were obtained by removing the culture medium after 9 hours, 2 days, 3 days and 4 days and on replacing the culture medium containing the PPARγ agonist and antagonist of PPARγ. As a PPARγ agonist used rivoglitazone [0,1 μm], and as an antagonist of PPARγ used 2-chloro-5-nitrobenzamide (GW-9662) [0.03 µm, 0.1 µm]. The above-mentioned concentration was obtained by dissolving each sample in DMSO and diluting thousandfold solution in culture medium. In addition, as a basic culture medium used culture medium containing only DMSO.

Five days after seeding of the cells was measured electrical resistance of the layer of epithelial cells, using the measurement system elec the historical resistance of the membrane (World Precision Instruments). As background values measured well, containing only the basic environment without epithelial cells of the cornea, and the obtained value is subtracted from the electrical resistance of the layer of epithelial cells. The resulting value was multiplied by the area of cell culture (0,33 cm2), thereby obtaining the electric resistance (Ω•cm2) per unit area.

(Result)

The electrical resistance of the membrane (average of four experiments) for each sample are shown in table 2.

Table 2
SampleThe electrical resistance of the membrane (Ω•cm2)
Rivoglitazone (0.1 ám)538,8
Rivoglitazone (0.1 ám) and GW-9662 (0.03 µm)473,5
Rivoglitazone (0.1 ám) and GW-9662 (0.1 ám)429,3
The basic culture mediumof 434.1

(Discussion)

From table 2 it is seen that the barrier function reinforced rivoglitazone (PPARγ agonist), decreased depending on the concentration under the action of GW-9662 (PPARγ antagonist), and the gain is completely suppressed p and the concentration of 0.1 mm. In other words, it was shown that the effect of the gain rivoglitazone the barrier function of the epithelial cells of the cornea is PPARγ-dependent. From the above results it is clear that if the connection has PPARγ-agonist activity, it may enhance the barrier function of epithelial cells of the cornea.

[Examples of the pharmaceutical composition]

Samples of pharmaceutical products using a PPARγ agonist described below.

Sample preparation 1

100 ml:

Rivoglitazone: 10 mg

Chloride sodium: 900 mg

Sterile purified water appropriate amount.

Changing the number of rivoglitazone, it is possible to prepare eye drops with different concentrations, such as 0.001% (weight/volume), in 0.01% (weight/volume), 0,03% (weight/volume)of 0.1% (weight/volume), 0.3% (weight/volume), and 1.0% (weight/volume) and 3.0% (weight/volume).

Example product 2

100 ml:

DRF-2593: 100 mg

Chloride sodium: 800 mg

Disodium hydrogen phosphate: 100 mg

Sodium dihydrophosphate: relevant number

Sterile purified water appropriate amount.

Changing the number of DRF-2593, it is possible to prepare eye drops with different concentrations, such as 0.1% (weight/volume), 0.3% (weight/volume), 0.5 percent (weight/volume)and 1.5% (weight/volume) and 3% (weight/volume).

The example of the drug 3

In 100 g:

Rivoglitazone: 0.3 g

Liquid paraffin: 10.0 g

White vaseline: the corresponding quantity is STV.

Changing the number of rivoglitazone, you can make eye ointment with different concentrations, such as 1% (by weight) and 3% (by weight).

Sample preparation 4

In 100 g:

GW-544: 0.3 g

Liquid paraffin: 10.0 g

White vaseline: the appropriate number.

Changing the number GW-544, you can make eye ointment with different concentrations, such as 1% (by weight) and 3% (by weight).

Industrial applicability

Connection functioning as a PPARγ agonist, significantly enhances the barrier function of the corneal epithelium. By strengthening the barrier function of the corneal epithelium, for example, it becomes possible prevention or treatment of eye infections associated with a decrease in the barrier function of the epithelium of the cornea, improving ocular discomfort associated with a decrease in the barrier function of the corneal epithelium, and the restoration of disturbed interaction between the epithelium of the cornea and lacrimal fluid to prevent functional decline in visual acuity.

1. Agent for strengthening the barrier function of the corneal epithelium, containing as active ingredient at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione(rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and salt.

2. Prophylactic or therapeutic agent against eye infections associated with the decrease in the barrier function of the corneal epithelium, containing as active ingredient at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione(pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and salt.

3. Agent for improving ocular discomfort associated with a decrease in the barrier function of the corneal epithelium, containing as active ingredient at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]labels and]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and salt.

4. Agent for recovery of functional visual acuity, containing as active ingredient at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and salt.

5. A method of treating diseases associated with decrease in the barrier function of the corneal epithelium, including the stage of the introduction to the patient a pharmacologically effective amount of at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-ylethoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-di is Idro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts.

6. The method of prevention or treatment of eye infection that is associated with the decrease in the barrier function of the corneal epithelium, including the stage of the introduction to the patient a pharmacologically effective amount of at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy] benzyl]-2,4-thiazolidinedione(rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts.

7. A method of treating eye discomfort associated with a decrease in the barrier function of the corneal epithelium, including the introduction to the patient a pharmacologically effective amount of at least one of 5-[4-(6-methoxy-1-m is l-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts.

8. The method of treatment for functional recovery of visual acuity, including the stage of the introduction to the patient a pharmacologically effective amount of at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione(rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts.

9. Applying at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione(rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]metox is]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts for the manufacture of an agent for improving the barrier function of the corneal epithelium.

10. Applying at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione(pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine(GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts to obtain an agent for prevention or treatment of eye infection that is associated with the decrease in the barrier function of the corneal epithelium.

11. Applying at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione (rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]t is solidin-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine(GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts to obtain the agent for improving ocular discomfort associated with a decrease in the barrier function of the corneal epithelium.

12. Applying at least one of 5-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-yl-methoxy)benzyl]thiazolidin-2,4-dione(rivoglitazone), 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-hintline]methoxy]phenylmethyl]thiazolidine-2,4-dione (DRF-2593), 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (pioglitazone), 5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione(rosiglitazone), N-[1-methyl-3-oxo-3-phenyl-1(Z)-propenyl]-O-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-L-tyrosine (GW-544), N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine (BMS-298585) and their salts to obtain the agent to restore the functional visual acuity.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely biopharmaceutics and may be used for preparing an immunogenic conjugate. That is ensured by: (a) a reaction of serotype 1 purified polysaccharide with an alkaline buffer to prepare serotype 1 partially des-O-acetylated polysaccharide; (b) a reaction of serotype 1 partially des-O-acetylated polysaccharide and a weak acid to produce serotype 1 neutralised partially des-O-acetylated polysaccharide; (c) a reaction of serotype 1 neutralised partially des-O-acetylated polysaccharide and an oxidising agent to prepare serotype 1 activated polysaccharide; (d) mixing of serotype 1 activated polysaccharide and a carrier protein; (d') combined lyophilisation of mixed serotype 1 activated polysaccharide and the carrier protein before a reaction with a reducing agent; (e) reaction of mixed serotype 1 activated polysaccharide and the carrier protein with the reducing agent to prepare a serotype 1 activated polysaccharide/carrier protein conjugate; and (f) capping of unreacted aldehydes in the serotype 1 activated polysaccharide/carrier protein conjugate. What is also presented is a method for preparing a multivalent immunogenic composition.

EFFECT: group of inventions enables preparing the composition presented in the form of vaccines that decreases a number of severe pneumococcal diseases.

27 cl, 17 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to pharmaceutical compositions for treating or preventing C. difficile infection in an individual. The composition is presented in the form of a solid dosage form and contains a therapeutically effective amount in tiacumicine, a stabilising amount of one or more antioxidants, such as butylated hydroxytoluene, and optionally one or more pharmaceutically acceptable excipients. The invention also refers to a method of treating C. difficile associated diarrhea using the given composition.

EFFECT: compositions of the invention have a high stability and a long shelf life.

14 cl, 5 dwg, 4 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: there are presented antibodies specifically binding the lipid-associated antigen of M.hominis with the characterised amino acid and nucleotide sequences, as well as a method of treating a Mycoplasma M.hominis infection involving administering to said mammal a therapeutically effective amount of the nanoantibodies.

EFFECT: invention can find further application in treating the mycoplasma infection.

4 cl, 2 tbl, 6 ex, 5 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a pyridine thio-derivative of general formula (I) or pharmaceutically acceptable salts thereof: , where R1 and R2, respectively, denote a hydrogen atom; R3 and R4, respectively, denote a hydrogen atom or a C1-8alkyl group; X denotes -O- or -S-; Y denotes a C1-12alkyl group, which can be substituted with a substitute selected from a group consisting of a hydroxyl group, C1-8alkoxy group or -(R5-O)n-R6 (where R5 denotes a C1-5alkylene group, R6 denotes a C1-8-alkyl group which can be substituted with a halogen atom, and n denotes an integer from 1 to 2) and Z denotes a hydrogen atom. The invention also relates to pharmaceutical compositions based on said compounds, having antibacterial activity towards Helicobacter pyroli.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to prevent or treat diseases in which Helicobacter pylori participates, specifically gastritis, gastric ulcers, duodenal ulcers, gastric MALT lymphoma, hyperplastic gastric polyps or gastrointestinal malignant diseases.

10 cl, 3 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely biopharmaceutics, and may be used for making vaccines. For this purpose, the composition stabilising a polysaccharide-protein conjugate, contains: (1) buffer saline with said buffer having pKa approximately 3.5 to about 7.5, (2) polysorbate 80 in the final concentration of 0.001% to 0.05 wt/vol % of the composition, and (3) one or more polysaccharide-protein conjugates containing one or more pneumococcal polysaccharides. The group of inventions also relates to a syringe filled with the above composition.

EFFECT: use of this composition can improve the stability of the immunogenic compositions, and inhibit deposition thereof.

28 cl, 8 tbl, 7 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to a method for preparing a carbon sorbent with the antibacterial properties, and to the carbon sorbent with the antibacterial properties prepared by this method. The declared method involves impregnation of the carbon hemosorbent granules in an initiator solution in N-vinylpyrrolidone at pH 7.0-7.5 and a residual pressure of 15-20 mm Hg. The hemosorbent : initiator solution in N-vinylpyrrolidone ratio is 1:1.4-2.0. Then the temperature is raised to 65-75°C, kept at that temperature for 0.5-8 hours in an inert medium and washed in water from the residual monomer at room temperature.

EFFECT: carbon sorbent with the antibacterial properties prepared by the specified method represents the round granules, contains polyvinylpyrrolidone in an amount of 4,5-5,5% and is characterised by a specific surface adsorption of less than 50 m2/g and total pore volume of less than 0,30 cm3/g.

2 cl, 2 tbl, 1 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel medication for treatment of purulent-inflammatory processes of skin and mucous membranes of different etiology. Medication is made in form of gel and contains the following ingredients with the following ratio of components in g per 100 g: biocomplex of cobalt (II) with metronidasole 0.20-0.50. biocomplex of cobalt (II) with ampicillin 0.20-0.50, trimecaine 3.00-5.00, methyluracyl 1.00-3.00, dimexide 10.00, glycerol 5.00-10.00, hydrophilic base 3.00-7.00, water 77.60-64.00.

EFFECT: extension of assortment of wound-healing medications.

3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel medication for treatment of purulent-inflammatory processes of skin and mucous membranes of different etiology. Medication is made in form of gel and contains the following ingredients with the following ratio of components in g per 100 g: biocomplex of metronidazole with zinc 0.5-2.0, biocomplex of furacilinum with copper 0.1-0.2, trimecaine 3.0-5.0, vitamins (vitamin A, vitamin E, vitamin PP, vitamin C or their mixture) 0.1-1.0, dimexide 10.0, hydrogel of methylsiliconic acid 1.0-5.0, hydrophilic base 3.0-7.0, water 82.3-69.8.

EFFECT: extension of assortment of wound-healing medications.

2 tbl, 1 ex

FIELD: biotechnologies.

SUBSTANCE: new strain of bacteria Pasteurella trehalosi is proposed, where the specified bacteria are positive in respect to beta-haemolysis, positive in respect to oxidase, positive in respect to catalase, negative in respect to urease, positive in respect to nitrates, negative in respect to indole, MacConkey-positive, positive in respect to glucose, positive in respect to saccharose, positive in respect to mannitol, negative in respect to arabinose, negative in respect to cellobiose, positive in respect to xylose, negative in respect to salicin, negative in respect to ornithine, negative in respect to esculin, negative in respect to alpha-fucosidase, positive in respect to beta-galactosidase. Also the strain of bacteria Mannheimia haemolytica is proposed. These bacteria are deposited under registration numbers ATCC No. PTA-3667, ATCC No. PTA-3668, ATCC No. PTA-3669.

EFFECT: immunisation of chickens with the purpose to prevent disease caused by above bacteria.

7 cl, 22 dwg, 2 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new glycopeptide antibiotic derivative of formula (IV-1), a method for preparing it, and to intermediate compounds for preparing it.

EFFECT: glycopeptide derivative has antibacterial activity on a vancomycin-resistant bacterium.

14 cl, 51 tbl, 121 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used for inducing posterior detachment of vitreous body. For this purpose 0.1 ml of miniplasmin solution is introduced endovitreally in 4 mm from limb. Preliminarily before introduction, solution of buffer salts up to pH values of 6.8-8.0 with osmolarity 280-320 mOsm to concentration of miniplasmin in solution 1 mg/ml is added into miniplasmin, mixed, heated to temperature 37°C and kept at said temperature for from 5 to 15 minutes.

EFFECT: method ensures reduction of toxic impact on retina and vitreous body, improvement of proteolytic properties of miniplasmin and, therefore, more complete detachment of vitreous body with reduction of interference trauma.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to immunology. There are studied: a method of decreasing the load and of reducing the number of plaques in the layer of retinal ganglion cells, of reducing the total amount of soluble amyloid-beta in the layer of retinal ganglion cells and of maintaining or reducing intraocular pressure in a subject, as well as a method of preventing, treating and relieving the symptoms of ophthalmic diseases associated with amyloid-beta related pathological disorders or changes in tissues of the visual system, a diagnostic technique for such disease and predisposition thereto, and a method of monitoring the minimal residual ophthalmic disease associated with the amyloid-beta related pathological disorders or changes, involving administering the composition containing the anti-amyloid-beta antibody to the patient. The present invention can find further application in a therapy of the ophthalmic diseases.

EFFECT: what is presented is a pharmaceutical composition for treating the ophthalmic diseases containing the anti-amyloid-beta antibodies.

31 cl, 3 ex, 13 tbl, 20 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to ophthalmology. A method for increasing the stability of a prostaglandin composition comprising prostaglandin, a preserving agent and pharmaceutically acceptable excipients, wherein the method comprises a stage whereat: the prostaglandin composition specified in a group consisting of Travoprost, Latanoprost, Bimatoprost and Tafluprost is packaged in a reusable low-density polyethylene container made of a low-density polyethylene wherein said low-density polyethylene container represents a low-density polyethylene bottle prepared with the use of blow-fill-seal technology, wherein low-density polyethylene resin is specified in a group consisting of Purell PE 1810 E, Purell PE 1840 H, Purell PE 3020 D, Purell PE 3040 D, Purell PE 3220 D.

EFFECT: group of inventions provides the local reusable ocular administration, the stability of the composition at room temperature up to 25°C for more than twelve months.

18 cl, 5 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to field of medicine, in particular to ophthalmology. Medicinal compositions for intravitreal injections and methods of treating ophthalmological disorders are disclosed. Medicinal compositions represent suspensions on the basis of low-soluble medication, such as triamcinolone acetonide. Compositions of suspensions have relatively low viscosity and are easily extracted via needle of 27- or 30-gauge needle, but are highly flocculated and can be easily redispersed.

EFFECT: group of inventions ensures improvement of vitreos body visualisation in the course of vitrectomy, treatment of ophthalmological disorders.

20 cl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to field of ophthalmology. Described is application of compositions for reduction of intraocular pressure, which contain antocyanoside or including it extract, proantocyanidine or including it extract or their combinations.

EFFECT: group of inventions ensures effective application of compositions for reduction of intraocular pressure in patient.

30 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology and can be used for treatment of post-LASIK keratectasia. For this purpose in space under epithelial-stromal corneal flap round recess is made from periphery to optic zone (in central zone of cornea), into which hypotonic riboflavin solution is introduced. When thickness of cornea 400 mcm and more is reached, space is filled with 0.1% riboflavin solution on 20% solution of dextran T 500 until cornea is saturated with riboflavin. After that, ultrasonic irradiation of cornea is carried out with wavelength 365 nm with intensity 3 mW/cm2 for 30 min fractionally - 6 cycles 5 each 5 minutes long. During irradiation of cornea with ultrasonic waves riboflavin solution is instilled on cornea each 2-3 minutes, additionally riboflavin solution is introduced into recess under epithelial-stromal corneal flap each 5 minutes for constant support of riboflavin solution volume in intrastromal space.

EFFECT: method ensures increase of cornea thickness to required level due to creation of conditions for fast saturation of cornea with riboflavin solution, acceleration of healing process with reduction of risk of postoperative complications development to minimum.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a method of intraocular pressure reduction and to a method of pain control involving the administration of a therapeutic compound representing , or its tautomer or stereoisomer forms wherein X represents NH; n is equal to 2 or 3; Ra, Rb, Rc and Rd represent stable functional groups independently consisting of: 0 to 4 carbon atoms, 1 to 9 hydrogen atoms; and Re represents H or C1-4alkyl. Furthermore, the invention refers to a compound represented by formula , or to its tautomer or stereoisomer form.

EFFECT: new compound is prepared; besides, the known compounds to be applied in pain and glaucoma control are studied.

8 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to veterinary science, and concerns treating corneal diseases in dogs. For this purpose, mesenchymal cord and placental stem cells received after easy human delivery are used. The mesenchymal stem cells are introduced retrobulbarly in saline solution 1-2 ml containing 0.075-0.20×106 cell/kg. The cells are introduced 1-2 times annually.

EFFECT: method provides the effective treatment of corneal diseases in dogs by creating the depot stem cells in a close proximity to the lesion.

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and is intended for treatment of inflammatory and trophic cornea diseases. For this purpose silicone-hydrogel soft contact lens, covered from inner surface by silico-dried amnion, is placed on cornea. Amnion with diameter smaller than lens diameter is used. Amnion is fixed on lens by means of polyacrylamide film, saturated with medication. As such means, used is antibacterial, anti-inflammatory, regenerating medication.

EFFECT: method ensures elimination of amnion dislocation under lens and reduction of time of corneal defect epithelisation, which increases treatment efficiency.

3 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly ophthalmology, and aims at conservative treatment of dacryostenosis. Ofloxacin ophthalmic gel is introduced into a lachrymal duct. Ofloxacin ophthalmic gel 3ml is introduced every second day, 8-10 times.

EFFECT: method provides recovered patency of the lachrymal ducts and prevented recurrent postoperative stenosis following dacryorhinocystostomy, including due to mechanical dilatation of the duct by means of the gel the physical characteristics of which differ from those of tears.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are offered: a pharmaceutical composition for preventing or treating atherosclerosis, metabolic syndrome, diabetes, obesity or their symptoms, or the combinations thereof, containing a pharmaceutically effective amount of D-tagatose or a salt, sugar alcohol, hydrate, solvate, ester or amide thereof, and a pharmaceutically effective amount of a second pharmaceutically active agent containing stilbene or a stilbenoid component or any salt, alcohol, hydrate, ester, amide, polymorph, isomer thereof, or a combination thereof, a related method of treating or preventing these diseases, the use of said composition for preparing a medicine or vaccine for the same application and a food stuff containing a pharmaceutically effective amount of D-tagatose or a salt, sugar alcohol, hydrate, solvate, ester or amide thereof, and a pharmaceutically effective amount of a second pharmaceutically active agent containing stilbene or a stilbenoid component or a salt, alcohol, hydrate, ester, amide, polymorph, isomer thereof, or a combination thereof.

EFFECT: declared combination reduces blood plasma triglyceride, including in additional carbon diet.

30 cl, 3 ex

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