Composition and method for increasing blood glucose level

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical industry and concerns a composition for glucose delivery through an oral mucosa for increasing of glucose (sugar) blood level of an individual. The composition contains: a. effective amount of glucose, b. effective amount of sodium glycocholate, c. effective amount of a pharmaceutically acceptable carrier; the composition it is free from additional active pharmaceutical agents.

EFFECT: development of the effective method for increasing glucose (sugar) blood level.

13 cl, 9 ex, 4 tbl, 7 dwg

 

The SCOPE of the INVENTION

The present invention relates to compositions and methods for increasing the levels of glucose in the blood, also to devices containing compositions and their use.

The LEVEL of TECHNOLOGY

Hypoglycemia or low blood glucose (sugar) in the blood is a condition to be medicinal treatment that affects humans and other mammals. Hypoglycemia exists when the glucose levels in the blood are or become lower than normal (usually below 70 mg/DL and sometimes below 50 mg/DL). Hypoglycemia can occur when the insulin levels in plasma are increased to levels that are higher than normal, which leads to lowering the levels of glucose in the blood to levels not sufficient to provide enough energy for normal functioning of the body. Hypoglycemia can escalate because of exercise or other activities that require higher levels of glucose in the blood. Hypoglycemia is a well-studied side effects of drugs used in the treatment of diabetes, but can also be a side effect of other drugs or the result of other diseases, hormonal or enzyme deficiency or tumor. Hypoglycemia can also be caused by the aggravation of the and the of divebomb, healthy in other respects.

Hypoglycemia from mild to moderate forms can lead to symptoms that include one or more of the following symptoms: hunger, anxiety, tremors, sweating, dizziness, caused by light, dizziness, anxiety, weakness, difficulty speaking or concentration, nightmares, irritability, slurred speech, dizziness, activity, contrary to common sense, headache, pale skin color, tardiness or convulsive twitching, tingling around the mouth, fatigue and even seizures. If mild or moderate form of hypoglycemia is not immediately treated, it can develop into severe hypoglycemia. Severe hypoglycemia occurs when glucose levels in the blood decrease and remain low for too long. Severe hypoglycemia may be the reason that the brain becomes deprived of sufficient energy to function properly, which can lead to loss of consciousness, epileptic seizure, coma or death. Other effects include slurred speech, dizziness or irrational activity.

Hypoglycemia is also fairly common in newborn babies. Symptoms may include tremors, cyanosis, apnea, lipotherme is, low body (body), poor feeding, lethargy and seizures.

The most common causes of hypoglycemia include inadequate, with large intervals or skipping meals or snacks, excessive doses of insulin or other drugs against diabetes, such as sulfonylurea and meglitinides, increased activity or physical activity, and excessive alcohol consumption.

Individuals with repetitive or recurrent hypoglycemia can adapt to it, not showing symptoms of mild to moderate hypoglycemia. This adaptation is especially dangerous, because these individuals may be in a state of anxiety and can not detect any symptoms of hypoglycemia directly to a coma. The usual treatment for such individuals is the frequent blood tests to determine levels of glucose in the blood and increasing the levels of glucose in the blood when they get too low. Hypoglycemia can usually be treated is relatively fast and simple conversion of glucose levels in the blood of individuals to normal levels.

Treatment of hypoglycemia are well developed. The usual method is to ingestion of any form of sugar, such as fruit juice, glucose tablets, milk, sugar, honey, or hard candy, posleduyushim waiting for 15 minutes, to monitor how the symptoms decrease or glucose levels in the blood rise to an acceptable level. If symptoms persist or glucose levels in the blood continue to be below acceptable levels, the individual repeats the intake of sugar containing substances and again waits, watching the effect on the blood sugar level.

This conventional method is effective only if the time is not lost and the affected individual is able to take joint action and can chew and swallow. Accordingly, there remains a need in therapeutic compositions and methods of introduction, which can be conveniently used by third parties or themselves to enter with little training or without it.

The INVENTION

According to the first aspect of the invention provides a composition of glucose for delivery of glucose through the mucous membrane of the mouth to increase the level of glucose in blood of the individual, and the composition includes:

an effective amount of glucose,

an effective amount of at least one amplifier absorption selected from lecithin, hyaluronic acid, glycolic acid, lactic acid, chamomile extract, cucumber extract, oleic acid, linoleic acid, linolenic acid, monoline, monooleate, monolaurate, borage oil, evening primrose oil, menthol is, trihydroxychalcone, glycerol, polyglycerol, lysine, polylysine, triolein, simple polyoxyethylenated ethers, simple politicaleconomic esters, chenodeoxycholic, deoxycholic, salicylate alkali metal, a pharmaceutically acceptable edetate and their pharmaceutically acceptable salts and analogues, and

an effective amount of pharmaceutically acceptable carrier, where the composition does not contain any additional active pharmaceutical agents.

The mucous membrane of the mouth can be a mucous membrane of the cheeks.

The composition may contain glucose at a concentration of from 10 to 80% wt./wt., from 20 to 70% wt./wt. or from 30 to 60% wt./wt.

Power absorption may be present in a concentration of from 0.01 to 5% wt./wt., from 0.01 to 3% wt./wt. or from 0.01 to 1% wt./wt. The total concentration of the amplifier, absorption may be less than 10% wt./wt. or less than 5% wt./wt.

The composition may include glycocholate sodium, glycerin, sodium lauryl sulfate and/or polyoxyethylene sorbitan monooleate.

The carrier may be an aqueous solvent, such as purified water. Alternatively the carrier may be the basis of chewing gum.

The composition may further include at least one additional ingredient selected from corriente agents, coloring agents, to the sideboards and antimicrobial agents. In addition, the composition may include sodium benzoate as a preservative or antimicrobial agent.

According to the second aspect of the invention provides Neurocrine dosing device containing the composition according to the first aspect. A metering device may be a dispenser with the measured dose, which can be adapted for delivery of the composition in the form of droplets having a size of from 1 to 200 μm, or from 1 to 20 μm, and may be adapted for dispensing from 0.05 to 0.5 ml, 0.05 to 0.3 ml or 0.05 to 0.1 ml of the composition of glucose in the act of spray.

According to a third aspect of the invention provides a method of increasing the level of glucose in the blood of an individual comprising introducing an effective amount of the composition according to the first aspect of the mucous membrane of the mouth (e.g., gums) of the individual. The introduction may include spraying the composition in the mouth of an individual using neurotologic metering device (e.g. a device with a measured dose).

The method may include the introduction of 30 to 50 mg of glucose in the act of spraying from the metering device and may include the introduction of a total dose of from 150 to 300 mg, or from 175 to 200 mg of glucose per session dosing. Furthermore, the method may include the introduction of three to eight acts spraying session dosing.

the number of the composition of glucose, sprayed in the act of spraying may be from 0.05 to 0.5 ml, 0.05 to 0.3 ml or 0.05 to 0.1 ml.

According to a fourth aspect, the invention provides use of a composition according to the first aspect, when the level of glucose in the blood of the individual or in the treatment of hypoglycaemia in an individual.

Finally, according to the fourth aspect, the invention provides use of a composition according to the first aspect in the manufacture of a product for the treatment of hypoglycemia or low blood sugar levels.

The present invention provides a composition of glucose, in which glucose, at least in part, is encapsulated in the micelles formed by one or more of the proposed agents that enhance the absorption or amplifiers. Glucose may be present in the form of small monolabeled vesicles, large monolabeled vesicles, pallamallawa vesicles or regolamentari vesicles. Power absorption allows the glucose is quickly transported through the membranes of the mouth to raise levels of blood glucose in an individual that requires treatment. Membrane or mucous membranes of the mouth consist of gum, faringealni, lingual, sublingual or palatal mucosa. Sublingual mucous membrane includes a membrane of the ventral surface of the tongue and the base of p is a, the gingival mucosa is the lining or mucosa of the cheeks. Sublingual, buccal or other oral mucosa is relatively permeable, enabling rapid absorption composition of the present invention. Consequently, this method of increasing glucose levels in the blood of the individual is an effective, non-invasive and convenient.

BRIEF DESCRIPTION of DRAWINGS

Figure 1 shows the effect of oral administration of the composition of glucose according to the invention on glucose levels in the blood not to be resistant individuals with type II diabetes.

Figure 2 shows the effect of oral administration of the composition of glucose in the glucose level in the blood of resistant individuals with type II diabetes.

Figure 3 shows the effect of oral administration of the composition of glucose to glucose levels in the blood not to be resistant, healthy individuals.

Figure 4 shows the effect of oral administration of the composition of glucose in the glucose level in the blood resistant, healthy individuals.

Figure 5 shows the steps of oral administration of the composition of glucose containing 4 g of glucose, the glucose level in the blood of resistant healthy individuals, which was injected insulin in the amount of 0.11 IU/kg of body weight. The results of the treatment and placebo treatment, showing the ingestion of glucose tablets, the content is soup 4 g glucose, presented for comparison purposes.

Figure 6 shows the effect of oral administration of the composition of glucose, containing 8 g of glucose, the glucose level in the blood of resistant healthy individuals. The results of the treatment and placebo treatment, showing the ingestion of two glucose tablets containing 8 g of glucose, presented for comparison purposes.

7 shows the effect of oral administration of the composition of glucose containing 4 g of glucose, the glucose level in the blood of resistant healthy individuals. The results of the treatment and placebo treatment, showing the ingestion of 4 g of glucose, presented for comparison purposes.

DETAILED description of the INVENTION

Used here, the term "includes" means "includes without limitation". Thus, the drug or group that includes a number of ingredients may also include additional ingredients without special enumeration. Used here, the term "consisting essentially of" includes the above ingredients and such additional ingredients which do not affect the basic and new features of the invention. Basic and new features of the invention are the characteristics of absorption of glucose present in the present compositions, through the mucous membranes of the mouth (for example, through the buccal, pharyngeal the th, lingual, sublingual and palatal mucosa) and penetration into the bloodstream of the individual. Used here, the term "comprising" means "including only the above ingredients and any impurities usually present in them." Thus, the drug or group consists of a number of ingredients that may not include additional ingredients not specifically listed separately from impurities normally present in these ingredients.

Used here, the term "effective amount" means that amount necessary to effect the desired result, i.e. for a given increase of glucose level in blood of the individual at a desired speed of absorption of glucose through the membrane of the mouth. This number should be understood as having a therapeutic effect in the body of the individual.

It will be understood that the effective amount will vary depending on the composition of glucose, the nature and severity of hypoglycemia, being treated, and the individual being treated. To find out which components are "effective amount" of the composition of glucose for a particular individual, is within the skill of the physician practice in this area and based on the General guidelines proposed here.

All expressed the value of concentration (i.e. % wt./wt.), used in the present description, including the concentration in the claims, are present in terms of the total mass of the composition, unless indicated otherwise.

Used here, the term "individual" and "individual" means members of the animal Kingdom, including, but not limited to the above, people.

Used here, the term "active pharmaceutical agent" means an ingredient that is applicable in the treatment or prevention of disease, illness or abnormal condition in the body of man or animal, and includes glucose to treat hypoglycemia.

Farinella, sublingual, lingual, palatal or buccal mucosa together here means "oral mucosa". "Oral mucosa" means any of faringealni, sublingual, lingual, palatal and buccal mucous membranes.

Composition glucose

According to one variant of implementation of the composition of glucose is present in liquid form. The concentration of glucose in the composition may be in the range from 100 to 800 g of glucose per liter, preferably from 300 to 800 g of glucose per liter and more preferably approximately 500 g of glucose per liter. In the alternative case, the glucose may be present in a concentration of from 10 to 80% wt./wt. or from 30 to 60% wt./wt.

True to notice contains at least one power absorption to enhance the transport of glucose across membranes of the mouth. The amplifier serves to encapsulate glucose in the micelles. Mixed micelles are formed when using more than one amplifier absorption. Each amplifier absorption is present in a concentration of from 0.01 to 5, preferably from 0.01 to 2 and more preferably from 0.01 to 1% wt./wt. The total number of amplifiers absorption is less than 10, preferably less than 5 and more preferably less than 2% wt./wt.

In the compositions of the present invention can be applied alkylsulfate any alkali metal, provided that there are no compatibility issues. Preferably the alkyl is a C8-C22 alkyl, more preferably lauryl (12). You can use any alkaline metal, preferably is sodium. The concentration of alkylsulfate alkali metal, if present, is preferably from 0.01 to 3, from 0.01 to 2, and 0.01 to 1% wt./wt.

It will be clear that some amplifiers absorption are usually described fatty acids, bile acids or their salts. Particularly preferred power absorption is trihydroxyanthracene and its pharmaceutically acceptable salts (for example, glycocholate sodium). When applying glycocholate sodium is preferably present in a concentration of from 0.01 to 5, from 0.01 to 3, and from 0.01 to 1 wt./wt.%.

Glycerin is another whom they preferred amplifier absorption. If it is present, its concentration is from 0.01 to 15, from 0.01 to 10, from 0.01 to 5 and from 0.01 to 2% wt./wt.

Lecithin may be saturated or unsaturated and is preferably selected from the group consisting of phosphatidylcholine, phosphatidylserine, sphingomyelin, phosphatidylethanolamine, Catalina and lysolecithin.

Preferred salts of hyaluronic acid, hyaluronates are alkali metals, especially sodium hyaluronate, and the alkaline earth metal hyaluronates and hyaluronate aluminum.

Specifically, suitable amplifiers absorption include (i) glycerol, glycocholate sodium and sodium lauryl sulfate, (ii) glycerol, glycocholate sodium and polyoxyethylene sorbitan monooleate (sold in Association with the trademark Tween 80).

These compositions optionally contain a stabilizer, a preservative and/or antioxidatively compounds particularly suitable for this purpose because they not only stabilize the composition, but also protects against bacterial growth and promote absorption of the composition. Phenolic compounds, as will be clear, means a compound having one or more hydroxy groups attached directly to a benzene ring. Preferred phenolic compounds, according to the present invention include phenol, and METHYLPHENOL (also known to the to m-cresol), and mixtures thereof. Known preservatives sugar such as sodium benzoate, also can be used successfully. Antioxidants include ascorbylpalmitate, BHA and BHT.

It will be clear to experts in this field that coloring tools, flavouring agents, agents, taste masking, and a number of other, non-therapeutic compounds may also be included in the preparation. Conventional flavouring and taste masking agents include peppermint oil, menthol, synthetic flavouring agents with the smell of strawberry, orange, cherry, pomegranate, raspberry, grape, mango, banana, watermelon, chocolate, vanilla and other flavouring agents. When using menthol as one of enhancing absorption agents, obviously, it will also give the fragrance composition. Conventional coloring agent that can be applied, is a food dye (for example, red food dye).

Isotonic agent, such as glycerin or dibasic sodium phosphate, can also be added to the composition. Isotonic agent is used to keep the micelle in a composition. When using glycerin as one of enhancing absorption agents, it will also function as an isotonic agent. When using dibasic sodium phosphate as an isotonic agent, it will also serve for the ingibirovaniya the growth of bacteria; the pH of the present compositions glucose should usually be in the range of from 3.5 to 7. To establish the pH of the composition, if required, can be used hydrochloric acid, sodium hydroxide, or other known base or acid.

Compositions of the present invention can be stored at temperatures in the range from 15°C to 40°C and preferably from 15°C to 30°C.

The present composition of glucose is preferably in liquid form for injection spray. However, it can also produce other dosage forms change, among other things, used pharmaceutically acceptable carrier. For example, the present composition can be done in chewing gum, chewing gum with a liquid to a Central part, chewable tablets and pellets. Specialist in the field of pharmaceutical product must be able to produce the composition of these other medicines. It will be clear that the glucose contained in chewing gum, chewing gum with a liquid to a Central part, chewable tablets or pellets, injected through the membranes of the mouth (preferably), not through the membranes of the gastrointestinal tract. For that to happen, the composition is held in the mouth within a few minutes of time, which can easily be determined by simple experiment.

A method of manufacturing songs and glucose

The present invention provides a method of manufacturing a composition of glucose present invention. These compositions can be produced by mixing an aqueous solution of glucose at least one amplifier, absorption and other additives or ingredients. Glucose should be added in a quantity effective for the desired purpose. Amplifiers absorption can be added simultaneously or sequentially. Micelles will be formed in virtually any mix of ingredients, but preferably with vigorous stirring with a high speed homogenizing mixer with a high shear rate. All amplifiers absorption of glucose and other ingredients described above, are suitable for use in these methods.

According to one method, the composition is made by obtaining a glucose solution, obtaining the solution "excipient and mixing together two solutions. The solution excipient produced by adding one or more amplifiers, absorption, and any other ingredients (e.g., preservative, flavoring agent, coloring agent, etc.) to aqueous solvent (e.g., purified water).

Device for introduction

According to the invention variants liquid compositions glucose can be entered using a number known in the area and reaerosolized mechanical devices with spray pump. Such devices, you can enter the composition in the form of the spray or mist. The use of many such devices is that the possibility for contamination is minimized because the devices are offline.

Neuronally dispenser may include measuring pump with preset dose to deliver pre-determined amount of the composition of glucose, or it can be set by the user for delivery of different amounts of the composition of glucose. One benefit of using a device having a measuring pump (for example, the dispenser with the measured dose) is the ability to deliver the exact number of songs in each act of spraying. Preferably neuronally dispenser with the measured dose is pre-set to deliver a number that is less than the recommended dose (i.e., the portion of the dose), so that the individual could have more control over the amount of the composition of glucose, which is injected in one session. For example, the dispenser can be set so that each introduction or the act of spray from the dispenser was allocated approximately 50 mg of glucose. This way individuals can regulate the quantity entered at intervals of 50 mg. for Example, the individual may exercise 3 of the act of spraying in the case of low-dose or 5 acts spraying in the case of the higher the dose.

The device may vary in size as the volume of the container, and the size of the pump and, consequently, to vary the amount of composition introduced in the act of spraying or in the session. The dimensions of the container can be of different volumes range from 5 to 100 ml, or from 10 to 50 ml, or from 20 to 30 ml. Measuring the pump can be configured for delivery from 0.05 to 0.5 ml, or from 0.05 to 0.3, or from 0.05 to 0.1 ml in the act of spray.

Route of administration

The composition of glucose (in liquid form), according to the invention, can be implemented quickly and easily by the individual or a third party, after a short training or without it (if the individual is unconscious or incapable of concerted action to urgent care). Samovodene can be made "before exposure", i.e. the individual can continue introduction up until he felt the disappearance of the symptoms. In the alternative case, the introduction of a certain amount of the composition of glucose (for example, with the use of the metering device with the measured dose) may be followed by a waiting period to determine whether the symptoms disappear. The introduction is carried out by spraying the composition of glucose in the mouth reaerosolized metering device. Preferably the composition is sprayed into the oral cavity without inhalation, so that was rustavelis droplets, but do not enter into the lungs, and the glucose is absorbed through the membranes of the mouth or mucous membranes.

According to another method, if the individual is conscious and the composition is in the form of chewing gum (liquid Central part or not) or tablets, chewing gum or tablet chew and keep it in your mouth until then, until the desired increase in the level of glucose in the blood, as checked on the reduction or elimination of symptoms of lower blood sugar.

One variant of implementation of the composition of the present invention were made as follows:

Example 1: a composition of glucose, according to the present invention

Solution:

350 ml of purified water USP was heated to approximately 90°C. was Added 500 g of glucose. Mixed solution of water/glucose until then, until you dissolve all the glucose. Then the solution of water/glucose was allowed to cool to approximately room temperature, with stirring.

Solution:

Then as stirring to 100 ml of purified water USP was added 11 g of glycerin, 2 g glycocholate sodium, 500 mg of lauryl sodium, 500 mg sodium benzoate, 2 g of corrigent with the smell of orange, 2 g of corrigenda for artificial cooling (such as sold by the Swedish company Givaudan). Each ingredient was added and allowed to dissolve is before adding the next ingredient.

Then solutions a and b were combined and added to purified water USP to a final volume of 1 L. Then, the resulting composition glucose was stirred for 5 minutes and kept at a temperature of 15°C to 30°C.

The above data on the composition of glucose are shown in the following table:

Composition glucose

IngredientQuantity (g/ml)The amount (% wt./wt.)
Glucose0,500042,37
Glycerin0,01100,93
Glycocholate sodium0,00200,17
Sodium lauryl sulfate0,00050,04
Sodium benzoate0,00050,04
Corrigent with the smell of orange0,00200,17
Corrigent with cooling effect0,00200,17
Purified water USP How much you want to 1 mlHow much you want to 100

Example 2: Application of the composition of glucose in reaerosolized dosing device with the measured dose

5 ml of the composition of glucose, is shown in the table above in example 1 were loaded into Neurocrine dosing unit with pump, equipped with a submerged tube.

The composition of glucose sprayed from the metering device numerous times and measured the mass (total volume) of the composition of glucose, spray for the act of spraying. Found that the average weight is 0,084 g of the composition of glucose, with minimum weight 0,077 g and the maximum weight 0,088,

Calculated that the density of the composition of glucose is 1,1532 g/ml, Therefore, found that the average volume of the composition, dosing in the act of spraying is 0,073 ml, with a minimum amount 0,067 ml and the maximum amount 0,076 ml.

Based on the amount of glucose in the composition of glucose (500 g/l), calculated that the average calculated the amount of glucose in the act of spraying is 0.036 g, with a minimum amount of glucose 0,033 g and the maximum amount of glucose 0,038, actuation of the dosing device five times will, therefore, cause in the end, the introduction 0,180 g glucose, on average, with a minimum amount of approximately 0,165 g and m is xymalos approximately 0,190,

The present method and composition cause increased levels of glucose in the blood, as shown in the examples below.

Example 3: Effect of reference composition of glucose on neolodge individual with diabetes type II

The composition of glucose in example 1 was administered using a dosing device with the measured dose for example 2 negodnym individuals with type II diabetes and monitored glucose level in the blood.

The individual was independently introduced the song in the cheek region of the actuation of the dosing device five times, without inhalation or swallowing. The level of glucose in the blood was measured before, during and after injection using standard methods. The composition of glucose was administered shortly before the time point "0". The results are shown in table 1 and plotted in figure 1. Measurements show increased levels of glucose in the blood after 5 minutes, with peak concentrations of glucose in plasma is reached after 17 minutes.

Table 1
The impact of the introduction of the composition of glucose on neolodge individual with diabetes type II
Minutes after administrationthe level of blood glucose (mg/DL)
-3 109
0*111
2110
5116
8118
12120
17135
22132
27128
32118
37110
5295
*measured as soon as possible after the introduction of songs

Example 4: the impact of the introduction of the composition of glucose in the fasting individual with diabetes type II

The composition of glucose in example 1 was administered using a dosing device with the measured dose for example 2 hungry individual with type II diabetes and monitored glucose level in the blood. After fasting for 12 hours, the individual was independently introduced the song in the buccal cavity by the actuation of the dosing device five times, without inhalation and swallowing. At over blood glucose was measured before, during and after injection using standard methods. The composition of glucose was administered shortly before the time point "0". The results are shown in table 2 and plotted in figure 2. Measurements showed an almost instant increase in the level of glucose in the blood, and the peak concentration of glucose in plasma was reached after 40 minutes.

Table 2
The impact of the introduction of the composition of glucose in the fasting individual with diabetes type II
Minutes after administrationThe level of blood glucose (mg/DL)
-5160
0*174
10173
15183
20175
25178
Minutes after administrationThe level of blood glucose (mg/DL)
30185
35170
40212
50166
* measured as soon as possible after the introduction of songs

Example 5: the impact of the introduction of the composition of glucose at healthy neolodge individual

The composition of glucose in example 1 was administered using a dosing device with the measured dose for example 2 healthy megalobrama individual and monitored glucose level in the blood. The individual was independently introduced the song in the buccal cavity by the actuation of the dosing device five times, without inhalation or swallowing. The level of glucose in the blood was measured before, during and after injection using standard methods. The composition of glucose was administered shortly before the time point "0". The results are shown in table 3 and plotted in figure 3. Measurements showed increased levels of glucose in the blood after 4 minutes, with the first peak concentration of glucose in the blood was reached in about 27 minutes, and the second slightly higher peak concentration of glucose in plasma was reached in approximately 65 minutes.

Table 3
The impact of the introduction of the composition of glucose is as neolodge healthy individual
Minutes after administrationThe level of blood glucose (mg/DL)
-2104,4
1106,2
4to 113.4
6111,6
12to 113.4
21118,8
27to 112.4
34115,2
55117
65124,2
75to 113.4

Example 6: the impact of the introduction of the composition of glucose at healthy hungry individual

The composition of glucose in example 1 was administered using a dosing device with the measured dose for example 2 to a hungry, healthy individual, and monitored the level of glucose in the blood. After fasting for 12 hours, the individual was independently introduced the song in the buccal cavity by the actuation of the dosing device five times, without inhalation or swallowing. Glucose is Rove was measured before, during and after injection using standard methods. The composition of glucose was administered shortly before the time point "0". The results are shown in table 4 and plotted in figure 4. The measurements showed an increase of glucose in the blood after 5 minutes, with the first peak concentration of glucose in plasma was reached after 33 minutes, and the second slightly higher peak concentration of glucose in plasma was reached after 53 minutes.

102,6
Table 4
The impact of the introduction of the composition of glucose at healthy hungry individual
Minutes after administrationThe level of blood glucose (mg/DL)
0*99
5104,4
10102,6
15100,8
2097,2
25100,8
33108
38102,6
43
53106,2
* measured immediately after the introduction of songs

In the following examples 7-9, all subjects were starving in the evening from 8 o'clock in the afternoon until, until you have tested the following morning at 7 o'clock until noon.

Example 7: Glucodynamic after hypoglycemia caused by insulin (subcutaneous injection (sc) of 0.11 IU/kg of regular insulin), and the introduction of 4 grams of the composition of glucose and tablets weighing 4 grams at time 70 minutes

11 subjects were introduced to 0.11 IU/kg body weight of insulin by subcutaneous injection at time = 0 minutes. At time equal to 70 minutes, subjects were given a commercially available tablet glucose (glucose tablets with the aroma of orange Dex 4, manufactured AMG Medical Inc., Montreal, Quebec)containing 4 g of glucose. Subjects tablet chewed and swallowed. The levels of blood glucose (mg/DL) of the subjects were measured at intervals of time = 15 minutes.

On the second day the same 11 subjects were introduced to 0.11 IU/kg body weight of insulin at time = 0 minutes. At time equal to 70 minutes, subjects were given the composition of glucose, as described above, according to the present invention. The composition of glucose sprayed in the mouth with the use of standard neurotologic doziruyuschaya, equipped with a tube immersed in the liquid, glucose was absorbed through the membranes of the mouth, and the residual liquid was swallowed. The amount of the composition of glucose, entered and swallow was equivalent to 4 g of glucose. Glucose levels (mg/DL) subjects were measured at intervals of time = 15 minutes.

To allow comparison with placebo on the third day of the 12 subjects, seven of which participated in the above tests, did not receive insulin, glucose tablets or composition of glucose present invention. The levels of glucose in their blood just was measured at regular intervals starting from time = 10 minutes.

The values of glucose levels in the blood below and plotted in figure 5.

Glucodynamic after induced by insulin hypoglycemia (subcutaneous injection (sc) of 0.11 IU/kg mass standard insulin) and the introduction of 4 g of the composition of glucose and glucose tablets, 4 g, at time +70 minutes

SD = standard deviation

Figure 5 shows the results of comparison of the composition of glucose present invention with glucose tablets or the superiority of performance glucose tablets under these test conditions.

Example 8: Comparison of glucose tablets, g, composition of glucose, 8 g, and placebo

12 subjects were given above in the text composition of glucose, according to the present invention. The composition of glucose sprayed in the mouth with the use of standard neurotologic dosing device provided with a tube lowered into the liquid, glucose was absorbed through the membranes of the mouth, and the residual liquid was swallowed. The amount of the composition of glucose, entered and swallow, equivalent to 8 g of glucose. The levels of blood glucose (mg/DL) was measured at intervals of time = -10 minutes.

On the second day of the 12 subjects were given two produced in industry tablets glucose (glucose tablets with the aroma of orange, Dex 4, manufactured AMG Medical Inc., Montreal, Quebec), each of which contained 4 g of glucose. Subjects tablet chewed and swallowed. The levels of blood glucose (mg/DL) of the subjects were measured at intervals of time = -10 minutes.

The values of glucose levels in the blood below and plotted in Fig.6.

Comparison between glucose tablets, composition, glucose, 8 g, and placebo, introduced healthy volunteers

SD = standard deviation

Figure 6 shows that the composition of glucose present invention is comparable with glucose tablets or better, chemtable glucose functions induced gluodynamics response.

Example 9: Comparison between glucose tablets, 4 g, the composition of glucose, 4 g and placebo

12 subjects were given above in the text composition of glucose according to the present invention. The composition of glucose sprayed in the mouth with the use of standard neurotologic dosing device provided with a tube immersed in the liquid, glucose was absorbed through the membranes of the mouth, and the residual liquid was swallowed. The amount of the composition of glucose, entered and swallow, was equivalent to 4 g of glucose. The levels of blood glucose (mg/DL) of the subject was measured at intervals of time = -10 minutes.

On the second day, 12 subjects gave manufactured in industry tablet glucose (glucose tablets with the aroma of orange, Dex 4, manufactured AMG Medical Inc., Montreal, Quebec)containing 4 g of glucose. Subjects tablet chewed and swallowed. The levels of blood glucose (mg/DL) of the subjects were measured at intervals of time = -10 minutes.

To provide a comparison with placebo, on the third day of the 12 subjects did not give glucose tablets or composition of glucose present invention. The levels of glucose in their blood just was measured at regular intervals starting from time = -10 minutes.

The mean values of glucose levels in the blood below and plotted in Fig.7.

Comparison of m is waiting for the glucose tablets, composition of glucose, 4 g, and placebo, introduced healthy volunteers

SD = standard deviation

7 shows that the composition of glucose present invention is comparable with glucose tablets or better than glucose tablets in function induced gluodynamics response.

The preceding description is presented only as an example and should not be construed as limiting the scope of the invention as described hereinafter in the claims.

1. Composition for delivery of glucose through the mucous membrane of the mouth to increase the level of glucose in blood of the individual, including:
a. an effective amount of glucose
b. an effective amount glycocholate sodium
c. an effective amount of pharmaceutically acceptable carrier, which composition is free from additional active pharmaceutical agents.

2. The composition according to claim 1, where the mucous membrane of the mouth is a mucous membrane of the cheeks.

3. The composition according to claim 1 where the glucose is present in a concentration of from 10 to 80 wt./wt.%.

4. The composition according to claim 1, where the glucose is present in a concentration of from 20 to 70 wt./wt.%.

5. The composition according to claim 4, where the glucose is present in a concentration of from 30 to 60 wt./wt.%.

6. The composition according to claim 1, where glycocholate sodium is present in concentric and from 0.01 to 5 wt./wt.%.

7. The composition according to claim 6, where glycocholate sodium is present in a concentration of from 0.01 to 3 wt./wt.%.

8. The composition according to claim 7, where glycocholate sodium is present in a concentration of from 0.01 to 1 wt./wt.%.

9. The composition according to claim 1, where the total concentration of glycocholate sodium is less than 10 wt./wt.%.

10. The composition according to claim 1, where the carrier is an aqueous solvent.

11. The composition according to claim 1, additionally comprising at least one additional ingredient selected from flavoring agents, coloring agents, preservatives and antimicrobial agents.

12. The composition according to claim 1, additionally comprising sodium benzoate as a preservative and antimicrobial agent.

13. The composition according to claim 1, where the carrier is the basis of chewing gum.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: medicine.

SUBSTANCE: present invention concerns new, selectable hybrid polypeptides expressing at least two hormonal activities containing a first biologically active module of a peptide hormone covalently bonded with at least one additional biologically active module of the peptide hormone.

EFFECT: polypeptides can be used as agents for treatment and prevention of metabolic diseases and disorders associated with overweight.

19 cl, 6 dwg, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new 2-alkylsufanyl-3-arylsufonyl-cycloalkano[e]pyrazolol[1,5-a]pyrimidines of general formula 1 or 2-alkylsufanyl-3-arylsufonyl-cycloalkano[d]pyrazolo[1,5-a]pyrimidines of general formula 2, which are antagonist of 5-HT6 receptors. In compounds of formula 1

and 2 ,

R1 is a hydrogen atom or C1-C3 alkyl; R2 is C1-C3 alkyl; R3 is a hydrogen atom, one or two optionally identical halogen atoms, C1-C3 alkyl or hydroxyl, optionally substituted with C1-C3 alkyl; n is an integer equal to 1, 2 or 3.

EFFECT: compounds can be used in preventing and treating diseases of the central nervous system, anxiolytics and as compounds with nootropic effect and suitable for enhancing memory.

12 cl, 1 dwg, 4 tbl, 9 ex

Diabetes treatment // 2363465

FIELD: medicine.

SUBSTANCE: present group of inventions relates to medicine, particularly to endocrinology. For this purpose sufficient amounts of a compound which inhibits HIF hydroxylase activity are introduced.

EFFECT: design of a method of treating diabetes and other conditions, related to glucose pathometabolism, through stabilisation of HIFα.

8 cl, 12 dwg

FIELD: medicine.

SUBSTANCE: invention refers to pharmacology. The method for improving amino acid absorption in a vertebrate, including a mammal and a bird, includes introduction to a vertebrate of AKG (alpha-ketoglutaric acid), mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in amount and/or at rate sufficient to maintain the desired effect. The method for decreasing plasma glucose absorption in a vertebrate, including a mammal and a bird, involves introduction to a vertebrate, including a mammal and a bird, of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in amount and/or at rate sufficient to maintain the desired effect of glucose absorption. The method of prevention, inhibition or relief of the condition with high-glucose plasma level in a vertebrate, including a mammal and a bird includes introduction to a vertebrate, including a mammal and a bird, of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in amount and/or at rate sufficient to maintain the desired effect on the specified condition.

EFFECT: application of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in therapeutically effective amount for making the composition used to prevent, relieve and treat the condition with high-glucose plasma level, application of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures for making the composition used to improve absorption, changed absorption, deteriorated absorption and disordered absorption of amino acids and/or peptides.

19 cl, 3 tbl, 3 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention claims bioactive agent in the form of compound of formula (I) , where n is 1 or 2, m is 0, q is 0, t is 0, R9 is hydrogen, A is phenyl substituted by 1 or 2 groups selected out of alkyl with 1 or 2 carbon atoms, X is -CH2CR12R13- group where each of R12 and R13 is hydrogen, Q is OR1, R1 is hydrogen or alkyl with 1 to 7 carbon atoms, and agent application in medicine manufacturing for treatment of state selected out of group including resistance syndrome and diabetes.

EFFECT: method of treatment for mammal subject with state selected out of insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver, cachexia, adiposity, atherosclerosis, and arteriosclerosis, involving daily oral administration of 1 to 400 mg of bioactive agent, and pharmaceutical composition based on the bioactive agent.

12 cl, 1 tbl, 2 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of diaminopyrrolo quinazoline of formula (I), which possess properties of protein tyrosine phosphatase PTP-1B inhibitors and can be used for reduction of glucose concentration in blood. In general formula (I) A stands for 5- or 6-member unsaturated or saturated hydrocarbon ring or 5- or 6-member unsaturated or saturated ring, which contains at least one heteroatom, selected from S, N or O, R1 represents hydrogen or lower alkyl; Ra represents hydrogen,

,

,

,

or lower alkyl , R1, Ra, Rb, Rc, Rd, Re, Rf are such as defined in invention formula.

EFFECT: obtaining derivatives of diaminopyrrolo quinazoline which possess properties of protein tyrosine phosphatase inhibitors.

32 cl, 5 dwg, 118 ex

FIELD: chemistry.

SUBSTANCE: invention concerns biotechnology, specifically production of new polypeptides regulating carbohydrate metabolism, and can be used in medicine. New polypeptides reacting as both GLP-1 receptor agonists and glucagon receptor antagonists. Polypeptides and coding nucleic acids are used as components of pharmaceutical compositions for treatment of diabetes type 2 and metabolism disorders.

EFFECT: production of compounds providing effective glucose homeostasis for patients, suffering from carbohydrate metabolism disorders.

18 cl, 1 dwg, 4 tbl, 20 ex

FIELD: medicine; endocrinology.

SUBSTANCE: invention refers to treatment pancreatic diabetes and related complications. Invention implies that method includes introduction of insulin susceptibility intensifier (excepting throglytasone) combined with one agent of group including inhibitor of aldose reductase, byhuanide, statin compounds, squalen synthesis inhibitor, fibrate compound, low-density lipoprotein (LDL) catabolism intensifier and angiotensin converting enzyme inhibitor.

EFFECT: lowered complication risk.

FIELD: medicine, endocrinology, pharmacy.

SUBSTANCE: invention relates to treatment of diabetes mellitus and complications associated with diabetes mellitus. Invention proposes using a pharmaceutical composition for prophylaxis and treatment of diabetes mellitus and associated complications. Pharmaceutical composition comprises an enhancer for sensitivity to insulin (but excluding troglitazone) in combination with at least component from group consisting of aldose reductase inhibitor, biguanide, statin compound and angiotensin-converting enzyme inhibitor. Proposed pharmaceutical composition offers the strong inhibitory effect with respect to diabetic hyperglycemia.

EFFECT: valuable medicinal properties of pharmaceutical composition.

30 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to drugs and concerns a pharmaceutical composition for percutaneous delivery of 4-hydroxy-tamoxsifen which contains 4-hydroxy-tamoxifen in an alcohol water solution where amount of spirit is 35-99.9 wt % of the composition weight, and about 45%-55%, about 46%-54%, about 47%-53%, about 48%-52%, about 49%-51% or about 50% of said 4-hydroxy-tamoxifen is found as an isomer Z and remained amount of said 4-hydroxy-tamoxifen is in the form of isomer E. There is also disclosed method for preparing a pharmaceutical composition for percutaneous delivery of 4-hydroxy-tamoxifen.

EFFECT: preparation of the pharmaceutical composition which contains an equilibrium ratio of isomers E and Z of 4-hydroxy-tamoxifen.

13 cl, 9 dwg, 4 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly to gynaecology, and covers therapy of vaginal infections. The offered method of vaginal infection treatment involves the stages of cleaning and cooling of a woman's perineum by applying a wet substratum containing a coolant and the stage of treatment by introduction of an active antimycotic component into vagina.

EFFECT: due to application of said cleaning and cooling compositions in combination with the antimycotic component, the method provides faster relief of pain, burning, itching and discomfort sensations associated with the vaginal infections.

16 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the chemical and pharmaceutical industry and to a composition of flowing heating lubricant, which contains from approximately 40 wt % to approximately 60 wt % glycerin, from approximately 40 wt % to approximately 60 wt % polyatomic alcohol; and from approximately 0.1 wt % to approximately 3 wt % non-ionic surfactant contained in the said mixture; where the flowing heating lubricant is basically anhydrous, forms a thin lubricating film on skin or condom and produces a calefacient effect when in contact with moisture. The lubricant essentially does not contain an insulating agent. Viscosity of such a composition is less than viscosity of glycerin and is greater than viscosity of polyatomic alcohol. Owing to this, there is faster formation of the useful thin layer on the surface with which the composition comes into contact; the surfactant improves wetting properties and flowing of the composition on the skin or condom.

EFFECT: composition can be added to a condom packaging and approximately after a week, it can distribute and almost completely cover the inner and outer surface of the condom.

22 cl, 7 tbl

FIELD: medicine.

SUBSTANCE: invention is related to chemical-pharmaceutical industry, and to medicine, namely to stomatology, and may be used as local agent in complex conservative therapy in treatment of inflammatory diseases of periodontium, in particular periodontitis in light, medium and severe form, and also in postoperational period in case of surgical procedure on periodontium. Agent is suggested for treatment of inflammatory diseases of periodontium on the basis of gelatin, which contains glycerin and water, and either of the following medicinal components - lincomycin, metronidazole, lidocaine and dexamethasone. Suggested agent has high medicinal properties due to active components (anti-inflammatory, antibacterial, anesthetic ones). Besides gelatin base provides for strong fixation on surface due to its own adhesion when wet, and the same property of gelatin brings ability to absorb pathological exudate in combination with haemostatic effect.

EFFECT: high viscosity of agent assists in durable release of dosage forms, which reduces number of agent intakes.

5 ex

FIELD: medicine.

SUBSTANCE: present invention concerns medical products, particularly a multivitamin syrup spray in aerosol package, containing vitamins A, D3, E, C, B1, B2, B6, niacinamide (vitamin B3), B12, folic acid, biotin, vitamin B5, maltitol, sorbite.

EFFECT: spray in aerosol package contains required vitamins and allows for effective deliver thereof to human body; vitamins get into blood directly from tunica mucosa of mouth escaping destructive effect of gastric acid.

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to pharmaceutical foamy compositions, virtually ethanol-free and including pimecrolimus in carrier-base, containing mixture of oily solvents, which constitutes at least up to 40% of total composition weight and includes: I) hexylene glycol; II) optionally oleyl alcohol and III) dimethylisosorbide and/or medium chain triglycerides; IV) in absence of oleyl alcohol, less than 10 % of water; V) at least one consistency-forming additive; VI) preservative; VII) at least one surface-active substance-emulsifier and VIII) propellant gas for foaming.

EFFECT: such compositions are indicated for application in treatment of various skin diseases, nail diseases and mucous tunic.

5 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to chemical and pharmaceutical industry, in particular to composition of nearly dry hot thickened flowable lubricant comprising glycerin mixture, polyatomic alcohol, nonionic surface-active agent and thickening agent carbomer, wherein surface-active agent improves wettability and ability of composition to flow on the skin and liquid rubber and thickening agent provides composition density and depth. This composition can be added to a condom package and cover nearly all internal and external surfaces of the condom within a week.

EFFECT: compound can be applied to skin or condom and can ensure optimal warning effect when contacting ambient moisture during the use of the compound.

10 cl, 12 tbl

FIELD: medicine.

SUBSTANCE: invention concerns stomatology area, and can be used for treatment of parodontium diseases. The agent for treatment of parodontium diseases as active substance of a phytogenesis contains a dry extract of leaves of a black currant, and also water, glycerin, water-soluble derivative of cellulose, calcium glycerophosphate, sodium fluoride, propyl paraben sodium salt, fructose, pepper mint oil.

EFFECT: expansion of assortment of the preparations applied to treatment of parodontium diseases, maintenance of mineralisation of teeth and cicatrisation of parodontal pockets, reduction of inflammatory phenomena in parodontium tissues.

3 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medical products and concerns pharmaceutical composition for treatment of the diseases associated with urokinase activator of plasminogen (u-PA) and/or with receptor of activator of urokinase plasminogen (u-PAR), containing: (i) amidino-, hydroxyamidino-, guanydino- and/or hydroxyguanydinophenylalanine derivative as an active material, (ii) mixed alcohol and polyol, and (iii) aqueous phase containing buffer solution. There is also disclosed stabilisation method of pharmaceutical composition.

EFFECT: physical and chemical stability.

25 cl, 6 dwg, 1 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: there is described oral pharmaceutical composition containing 9,10-dehydroepothilone combined with a pharmaceutically acceptable carrier. According to the second version, the oral pharmaceutical composition contains trans-9,10-degihydroepothilone D and a pharmaceutically acceptable carrier containing hydroxypropyl-β-cyclodextrine, ethanol and propylene glycol. The concentrate for injection contains 9,10-degihydroepothilone D in the pharmaceutically acceptable carrier.

EFFECT: good bioavailability of epothilone D.

21 cl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically to otorhinolaryngology and toracal surgery, and can be used for prevention and treatment of chronic cicatrical stenosis of larynx and trachea. To that end, mixture of diprospan (0.5 - 1.0 ml), longidasa (1500-3000 UI), 2% lidocain (0.04 g) and ketorolac (0.03 g) diluted to 5 ml with 10% glucose solution is administered retrosternally, peritracheally. The mixture is administered once a week, a course including 1-3 injections. 3-5 inhalations are performed with compressor nebuliser of longidasa 1500 ME dissolved in 3 ml of broncholytic or mucolytic medicine once a week in intervals between administrations.

EFFECT: increased therapeutic efficiency in stenoses treatment and restenosis process prevention due to improved lymph flow, blood flow, microcirculation, tissues trophism, prolonged anaesthesia and lowering of endotoxemia level leading to quick inflammation relief and prevention of excessive development of cicatrical and granulation tissue in larynx and trachea.

3 ex

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