Nasal introduction desmopressina

 

(57) Abstract:

The pharmaceutical composition is intended for one-time effective and creates a stable plasma levels of nasal introduction desmopressina. The composition is an aqueous solution having a volume of from 5 to 45 ál. The solution contains from 0.5 to 2 mg/ml compound selected from the group consisting of desmopressina, desmopressina acetate, and pharmaceutically acceptable salts desmopressina. Means for delivering desmopressina made in the form of a nasal spray pump or device, a multiple dosing for nasal drip injection desmopressina. The composition and the means used to treat urinary disorders such as diabetes insipidus, urinary incontinence, total incontinence and nocturnal enuresis. The invention provides stable plasma levels desmopressina when using small amounts of drugs, which leads to its economy. 3 S. and 9 C.p. f-crystals, 1 Il.

The invention relates to nasal introduction desmopressina, desmopressina acetate and other pharmaceutically acceptable salts desmopressina, as well as to the optimum compositions for such an introduction.

Nasal introduction predstavit problems associated with the creation of optimal conditions for intranasal deposition of peptide drugs, which must overcome the barrier of the nasal mucosa and into the systemic circulation, and must be delivered efficiently designed in peripheral target organs. In addition, the majority of known peptides suitable for nasal administration, the road, and at present there is a tendency to wasteful "excessive" the introduction of these expensive nasal peptides. Thus, there is a need to improve nasal administration of peptides.

It is known that the dosing using a nasal pump volumes of less than 50 μl unacceptable because it is impossible to guarantee the accuracy of dosing and opportunities for effective delivery to the organs-targets; on the other hand, a larger volume in excess of 150 μl, is considered unacceptable in this area, since it is known that it leads to zachlapywaniu (F. Moren, Aerosols in Medicine. Moren et al., Eds., page 346, Elsevier Scientific, Amsterdam (1993)).

There is a need for accurate delivery and economical system for effective nasal administration of peptides. In particular, there is a need for accurate and optimal delivery system for effectine is to create a pharmaceutical composition desmopressina, desmopressina acetate or other pharmaceutically acceptable salts desmopressina as a single dose for nasal administration, which represents an improvement, ensuring effective delivery to peripheral targets.

Another objective of this invention is to provide aqueous basic solution desmopressina, desmopressina acetate or salt desmopressina.

Another objective of this invention is to provide a tool for nasal introduction of water main solution desmopressina, desmopressina acetate or other pharmaceutically acceptable salts desmopressina for repeated and persistent dosing volume of 5 to 75 μl, more preferably the amount of from 10 to 50 μl, in particular volume from about 20 to 45 ál.

Another objective of this invention is to provide a method of nasal introducing convenient way desmopressina, desmopressina acetate or another pharmaceutically acceptable salt desmopressina, so persistent effective concentration is served in the plasma of the patient.

An additional objective of this invention is to provide a method of manufacturing a drug SREI, General enuresis and bedwetting.

These and other objectives will become apparent to experts in this field after reading the benefits of this proposal.

For the purposes of this description desmopressin (DDAVP) is a 1-(3-mercaptopropionic acid)-8-D-arginine-vasopressin. The term "nasal" includes the term "intranasal" which in this context means the delivery of drugs through the nasal mucosa.

The invention includes a pharmaceutical composition in the form of a single dose for nasal administration, which contains an aqueous solution having a volume of from about 5 to about 75 μl, and the solution contains from about 0.1 to about 2.0 mg/ml of the compounds selected from desmopressina, desmopressina acetate or a pharmaceutically acceptable salt desmopressina. The solution can have a volume from about 10 to about 50 μl, from about 20 to about 45 μl; or about 35 μl. The compound in the solution is from about 0.1 to about 0.5 mg/ml or from about 0.5 to about 2.0 mg/ml

The invention also includes a means for delivery together with nazalnam spray pump or device for nasal drip Vvedenie 0.1 to about 2.0 mg/ml desmopressina, desmopressina acetate or a pharmaceutically acceptable salt. The solution in the means of delivery has a volume of from about 10 to about 50 μl, from about 20 to about 45 μl; or about 35 μl.

Another aspect of the present invention is a method of supplying stable plasma levels of nasal entered desmopressina, desmopressina acetate or a pharmaceutically acceptable salt desmopressina, when the amount of from about 10 to about 50 μl of an aqueous solution containing desmopressin, desmopressina acetate or a pharmaceutically acceptable salt desmopressina in the range from about 0.1 to about 2.0 mg/ml in solution. This method is useful for the treatment of urinary disorders such as diabetes insipidus, urinary incontinence, total incontinence and nocturnal enuresis.

The drawing shows in graphical form the results of research conducted in connection with this invention.

In accordance with this invention proposed single dose of the pharmaceutical compositions in the form of aqueous solutions having a volume of from 5 to 75 μl and containing from 0.1 to 2.0 mg/ml desmopressina, desmopressina acetate or the corresponding molar amount of its pharmaceutically acceptable salts.

Metroactive, associated with diabetes insipidus, urinary incontinence and enuresis, particularly nocturnal enuresis.

The aqueous solution preferably has a volume of from 10 to 75 μl. A more preferred amount of from 15 to 50 µl and in particular the amount of from 20 to 45 ál. Regardless of the preferred volumes for the aqueous solution preferably, the concentration of desmopressina varied from 0.1 to 0.5 mg per 1 ml, or from 0.5 to 2.0 mg / 1 ml

In accordance with this invention proposed an airtight container, designed specifically for use with nazalnam spray pump or device for nasal drip injection for multiple dosing volume of 5 to 75 μl, more preferably the amount of from 10 to 50 μl, in particular volume from 20 to 45 µl of the aqueous basic solution desmopressina, desmopressina acetate or another pharmaceutically acceptable salt desmopressina.

Airtight container dispenses a single stable dose of a basic solution containing from 0.1 to 0.5 mg per 1 ml, or from 0.5 to 2.0 mg per 1 ml desmopressina acetate or the corresponding molar quantity desmopressina or other suitable pharmaceutically acceptable salts desmopressina. The spray pump and the AUX pump preferably is of type pumps with advanced compression and is designed to deliver an amount in the range from 5 to 75 μl.

The composition in the form of a single dose and the basic solution according to this invention may include controlling the osmotic pressure agents, such as sodium chloride; preservatives, such as chlorobutanol or benzylaniline; sautereau agent, such as sodium phosphate or sodium citrate buffers, designed to maintain a pH from about 4 to about 6, and preferably about 5; and agents that enhance the absorption, such as salts of bile acids, monolaurate esters of microholes and derivatives fusidate.

Other pharmaceutically acceptable solutions and compositions in an airtight container for use with a spray pump or device for nasal drip injection for dispensing a single dose of the pharmaceutical composition desmopressina, desmopressina acetate or other pharmaceutically acceptable salts desmopressina in molar bands, equivalent to the one described here, are also included in the scope of this invention.

Also describes the manufacture of a medicinal product for the treatment of urinary disorders selected from the group consisting of diabetes insipidus, urinary incontinence, total incontinence and bedwetting, and this drug is efticiency acceptable salt desmopressina, and this medicinal product includes from about 10 to about 75 μl of an aqueous solution containing a specified compound in the range from about 0.1 to about 2.0 mg/ml of the indicated solution.

The invention is based on the data that intranasal introduction desmopressina acetate at a concentration of about 1.5 mg/ml results in essentially the same concentration profile desmopressina plasma, regardless of the input number, in the range from 25 to 100 ál for adults, and is equally effective in this band introduction. This model extends even into even smaller amounts: for adults, such as from 10 to 15 μl, and for children by volume of less than 10 μl, such as the amount of about 5 to 7 µl.

Currently available on the market measuring spray pumps unsuitable for reproducible dosing volumes less than about 50 μl. This is a consequence of the lack of incentive for the development and sale of such pumps, as the ratio of volume/concentration/plasma levels desmopressina in accordance with this invention is described for the first time exclusively in this description.

Following the example of demonstriruet the different concentrations desmopressina acetate.

Example. Prepared basic solution containing 0.3 mg desmopressina acetate in 1 ml of distilled water. Six healthy male volunteers were administered different doses of this basic solution. The introduction was made in the form of a nasal spray using the measured spray pumps, equipped with spray nozzles.

In each nostril each volunteer was administered in the following doses: 75 μg in 25 μl, 150 μg in 50 μl, 210 mcg 70 ál and 300 µg in 100 µl. The combined results are summarized in the shown in the drawing the graph. While in the plasma profile desmopressina had individual variances, the ratio of the amount of dose/plasma profile was essentially the same for all examined persons

The drawing shows that within the investigated dose range effect of the plasma level does not depend on the injected volume of solution desmopressina with a certain concentration desmopressina acetate (1.5 mcg/ml). This attitude persists also for a wider range of concentrations, such as from 0.1 to 2 μg/μl, and for desmopressina and its pharmaceutically acceptable salts in addition to acetate.

Based on this description may be applicable to the Xia as included in the scope of the present invention, as defined by the claims.

1. Pharmaceutical composition in the form of a single dose for nasal administration, which is an aqueous solution having a volume of from about 5 to about 45 μl, and this solution contains from about 0.5 to about 2.0 mg/ml compound selected from the group consisting of desmopressina, desmopressina acetate, and pharmaceutically acceptable salts desmopressina.

2. The composition according to p. 1, characterized in that said solution has a volume of from about 10 to about 45 μl.

3. The composition according to p. 1, characterized in that said solution has a volume of from about 20 to about 45 μl.

4. The composition according to p. 1, characterized in that said solution has a volume of about 35 ml.

5. Composition under item 1 for the treatment of urinary disorders selected from the group consisting of diabetes insipidus, urinary incontinence, total incontinence and bedwetting.

6. Means for delivering desmopressina in the form of a nasal spray pump or device for nasal drip injection during repeated dosing volume from about 5 to about 45 μl of an aqueous solution containing from about 0.5 to about 2.0 mg/ml desmopressin the tives such as those that this solution has a volume of from about 10 to about 45 μl.

8. Means on p. 6, characterized in that said solution has a volume of from about 20 to about 45 μl.

9. Means on p. 6, characterized in that said solution has a volume of about 35 ml.

10. A method of obtaining a stable plasma levels desmopressina by nasal introduction of compounds selected from the group consisting of desmopressina, desmopressina acetate, and pharmaceutically acceptable salts desmopressina, in the amount of from about 10 to about 45 μl of an aqueous solution containing a specified compound in the range from about 0.5 to about 2.0 mg/ml of the indicated solution.

11. The method according to p. 10, characterized in that the specified volume is in the range from about 20 to about 45 μl.

12. The method according to p. 10 for the treatment of urinary disorders selected from the group consisting of diabetes insipidus, urinary incontinence, total incontinence and bedwetting.

 

Same patents:

The invention relates to biotechnology, in particular genetic and protein engineering

Drops heart // 2169577
The invention relates to pharmaceutical industry and can be used for the treatment of patients with cardiovascular disease (CLO), cardiac tachyarrhythmias, angina pectoris, arterial hypertension

The invention relates to medicine extraordinary actions containing organic active ingredients

The invention relates to chemical-pharmaceutical industry, refers to a stable solution palmitate, treatment of skin diseases and reducing the side effects of chemotherapy for cancer patients

The invention relates to medicine and pharmaceutical industry, in particular to the creation, production and application of funds for the treatment of cardiovascular diseases
The invention relates to medicine
The invention relates to medicine, namely to create tools for the treatment of alcohol intoxication

Bactericidal togel // 2157206
The invention relates to medicine, namely to bactericidal hotovely

The invention relates to medicine, namely to endocrinology and purulent surgery

The invention relates to medicine

The invention relates to pharmaceutical industry and relates to aqueous compositions for nasal aerosol introduction synthetic analogue of vasopressin-desmopressina

The invention relates to medicine, namely, neurology, and may find application in speech therapy

The invention relates to medicine, namely to dermatology, and relates to a medicine for the prevention and treatment of prematurely aging skin
The invention relates to new compounds, Penta-, hepta the nonapeptide sequence of oxytocin, which can find use as intermediates for the synthesis of oxytocin and related compounds, for example dezaminooksitotsina used in biology and medicine

FIELD: veterinary science.

SUBSTANCE: one should inject ozonized isotonic sodium chloride solution intravenously for cows at the dosage of 1000.0 ml at the presence of 2.2 ml ozone and 50 U oxytocin intramuscularly not later than 3 h against the moment of a calf's birth. The innovation enables to decrease the quantity of retention of afterbirth cases in recovered animals.

EFFECT: higher efficiency.

2 tbl

Up!