The invention relates to a system for determining a suitability of an active ingredient for transdermal and/or transmucosal application.
The transdermal application of active ingredients is known. The best known example is the nicotine patch. This is stuck onto the skin where it releases the active ingredient in a controlled manner which is then resorbed via the skin. The active ingredient passes into the blood vessel system without being prematurely broken down in the gastrointestinal tract or in the liver. The concept of the transdermal therapeutic system is also used synonymously
Likewise, the application or administration of active ingredients via the mucous membranes (mucosae) is known. An example of transmucosal application is a lozenge which is taken orally, but is not swallowed but left in the mouth to dissolve. Transmucosal therapeutic systems are preferably used when the area of action of the active ingredient is in the oropharynx (for example local anaesthetics and anti-inflammatory drugs), or when the active ingredient is to pass directly into the bloodstream via the mucous membrane. The latter has two advantages. Firstly, the medication passes very quickly into the bloodstream and secondly, the portal system of the liver can be bypassed in this manner.
In research, a particular problem lies in predicting whether a specific active ingredient can be applied transdermally and/or transmucosally. Expensive clinical studies are often required to establish that a transdermal or a transmucosal application is not indicated for a particular case of use. A further problem is seen in the generation of known models which allow a prediction. The machine processing of corresponding models is computationally intensive and requires a large number of records. The results are inaccurate and difficult to classify.
Based on this prior art, the aim of the present invention is to provide an improved system for determining a suitability of an active ingredient for transdermal or transmucosal application.
This aim is addressed according to the invention by a system according to claim 1 and by a method according to claim 10.
Especially, the aim is addressed by a system for determining a suitability of an active ingredient for transdermal or transmucosal application, the system comprising:
An especial advantage of this system is that the suitability can be simply assessed by means of a data processing device, namely by the computing unit. Naturally, a prediction of the suitability of a particular active ingredient for transdermal or transmucosal application cannot replace clinical studies. However, an advantage of the system according to the invention is seen in recognising, at an early stage, candidates who are completely unsuitable for a respective application.
In an embodiment, the computing unit is configured to form a weighted average via a plurality of characteristic numbers in order to assess the suitability. The stated and/or stored data preferably lead to characteristic numbers which indicate the suitability of the active ingredient for transdermal or transmucosal application in individual subject areas. According to the invention, an especially weighted averaging is to be carried out via the plurality of characteristic numbers. For example, it is possible for at least four or six or eight or ten characteristic numbers to be averaged to produce an overall result to indicate the suitability of a particular active ingredient for transdermal or transmucosal application. This plurality of parameters leads to a robust and informative result.
The computing unit can be configured to determine the/a characteristic number, while considering in each case one of the following items of information:
These items of information are especially significant for transdermal application, but essentially also for transmucosal application and can be simply and efficiently processed by the computing unit.
At least some of the characteristic numbers can be a selection of numbers from the set of whole numbers. Ultimately, it is possible to map the provided items of information, for example concerning the structural formula, onto an index value or a characteristic number. This characteristic number can preferably be a whole number, thereby producing simple and informative results. In a further preferred embodiment, the characteristic numbers are a selection of integral numbers within a predetermined interval. This set preferably has a relatively low cardinality. For example, this set can contain less than 15 elements or less than 10 elements or less than 7 elements. In one embodiment, the set comprises the following (characteristic) numbers {−3, −2, −1, 0, 1, 2, 3}, in another embodiment it comprises the (characteristic) numbers {−5, −4, −3, −2, −1, 0, 1, 2, 3, 4, 5} or also {0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10}. Likewise, decimal numbers can be used as characteristic numbers, for example with an accuracy of one decimal place.
The computing unit can be configured, in assessing the suitability of the active ingredient, to consider
As already stated, a weighted averaging is preferably carried out via the characteristic numbers. The structural formula and/or the bioavailability and the dose can be taken into especial consideration in the result concerning the transdermal and/or transmucosal suitability. In one embodiment, the associated characteristic numbers can influence up to a maximum of 30% of the result. The structural formula and the bioavailability and dose preferably find their way into the overall result with at least 5%.
The computing unit can be configured, in assessing the suitability of the active ingredient, to consider
The mentioned items of information are important for the overall result. However, it can be advantageous to consider them with a lower weighting. In a preferred embodiment, this weighting is within a range of 3 to 10% per characteristic number. This weighting can result in an especially efficient assessment.
In an embodiment, the database can comprise mapping tables for mapping individual items of information onto characteristic numbers. For example, the mapping tables can state intervals when a particular item of information is assigned to a particular characteristic number. Mapping tables for mapping the
In a further embodiment, there is a single mapping table which provides mappings onto corresponding characteristic numbers for a plurality of items of information.
The system can comprise at least one measuring device for determining the molecular weight and/or the acid strength and/or the water solubility and/or the melting point. Thus, the system can preferably determine some of the parameters independently and take these into consideration when assessing the suitability of the active ingredient for transdermal or transmucosal application.
Furthermore, the mentioned object is achieved by a method for determining a suitability of an active ingredient according to claim 9.
Especially, the aim is achieved by a method for determining a suitability of an active ingredient for transdermal or transmucosal application, the method comprising the following steps:
These steps are preferably carried out by the system which has already been described. Advantages similar to those which have already been described in connection with the device are obtained.
The data which are taken into consideration in the method can comprise:
The method preferably comprises a step for reading out at least one characteristic number from a/the database. This characteristic number can be determined while considering the mentioned items of information. The database provides intervals in order to map the items of information onto specific characteristic numbers.
The method can comprise a step for comparing the weighted average with a threshold value. This comparison preferably results in a particular active ingredient being considered suitable or unsuitable for transdermal or transmucosal application. In one embodiment, a particular active ingredient is considered as being suitable for transdermal or transmucosal application if the weighted average is greater than a threshold value, especially if it is greater than 0 or 1.
Furthermore, the aim can be addressed by a computer-readable medium with instructions for implementing one of the described methods. The instructions are intended to be carried out on a computer.
Further advantageous embodiments are revealed in the subclaims.
In the following, the invention is described using several embodiments which are described in more detail with reference to drawings.
An output device 103 of the system 100 can display the results or can request a user to input data. For example, the user can be requested to provide information concerning the above-mentioned parameters.
In an embodiment, some of these items of information have already been stored in the database 110 and can be retrieved, for example, by entering the name of the active ingredient.
The system 100 optionally has a measuring device 104 which records at least some of the items of information which have already been mentioned and can provide them to be further processed by the computing unit 102. For example, this can be a device for determining the melting point, a spectral analysis device and similar devices.
In an embodiment, after the items of information have been acquired by the computing unit 102, they are mapped onto characteristic numbers. A corresponding mapping can be carried out by a calculation specification.
In an embodiment, the computing unit 102 uses the database 110 to carry out a suitable mapping. For example, an item of information concerning the half-life period can be used in order to establish an associated characteristic number from a half-life period mapping table 111 which is stored in the database 110.
Structurally, the half-life period mapping table 111 is generated so that it has two columns, the first column stating the parameter value of the half-life period “T½” and the second column stating the “characteristic number”. Apart from the header line, the half-life period mapping table 111 comprises seven further lines which are suitable for defining intervals for parameters and for allocating a particular characteristic number thereto. In the illustrated embodiment, the half-life period mapping table 111 is to be interpreted such that characteristic number 3 is assigned to the interval: 0 to less than 10 h(=hours), characteristic number 2 is assigned to the interval: 10 to less than 15 h, characteristic number 1 is assigned to the interval: 15 to less than 20 h, characteristic number 0 is assigned to the interval: 20 to less than 25 h, characteristic number −1 is assigned to the interval: 25 to less than 30 h, characteristic number −2 is assigned to the interval: 30 to less than 35 and characteristic number −3 is assigned to the interval: greater than 35 h.
For example, if an active ingredient has a half-life period of 9 h, the computing unit 102 would assign it characteristic number 3 by means of the half-life period mapping table 111.
The computing unit is configured to establish a characteristic number for each predetermined parameter or for each item of information concerning the active ingredient and to average these characteristic numbers according to a weighting specification. For example, the characteristic number for the structural formula with approximately 20% and the daily dose with approximately 15% can assume a prominent role in assessing the overall result. With a slightly lower weighting (for example approximately 10%), a characteristic number concerning the acid strength of the active ingredient, a melting point, a water solubility and a risk of forming skin irritations (skin irritation potential) can be considered. With an even lower weighting (for example 5%), characteristic numbers which indicate the half-life period, the water solubility and the metabolism can be considered.
For example, if the method according to the invention is applied to the active ingredient nicotine, the following results are obtained. Nicotine has a molecular weight of 62 g/mol, its melting point is −79° C. and its pKA value is 8.9. The half-life period of nicotine is between 1 and 6 h, a log P value of 1.17 being calculated. The required daily dose is usually between 7 and 21 mg and an efficiency of 20-45% is assumed for oral administration.
The following characteristic numbers are obtained for nicotine according to the method of the invention:
Therefore, overall a weighted average of approximately 2.4 is obtained. The weighted average is thus positive, which indicates that a particular active ingredient, in this example nicotine, is suitable for transdermal application. In this embodiment, a weighted average greater than the threshold value of 2 shows that this is a very suitable active ingredient.
In contrast thereto, when the active ingredient Enalapril is assessed, the method according to the invention produces a weighted average of approximately −1. The negative result indicates that this active ingredient is rather unsuitable for transdermal application.
The described method is implemented partly or fully by the computing unit 102.
The described system can likewise be used to establish the suitability of a particular active ingredient for transmucosal application.
100 system
101 input device
102 computing unit
103 output device
104 measuring device
110 database
111 half-life period mapping table
Number | Date | Country | Kind |
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14156479.9 | Feb 2014 | EP | regional |
Number | Date | Country | |
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Parent | 15118757 | Aug 2016 | US |
Child | 17303519 | US |