Packaging for hydrophilic medical instruments

European).

EP 1 894 525 Β1

V6054PL00 / UK

Description [0001J The invention relates to plastic packaging for hydrophilic medical instruments, in particular hydrophilic coated lancets, providing hydrophilicity of the surrounding object for a long time.

[0002] In medical diagnostics, the examination of blood or interstitial fluid samples enables early and reliable detection of pathological conditions as well as targeted and proven control of the body's condition. Medical diagnostics involves constantly obtaining a sample from the blood or interstitial fluid of the subject.

[0003] In order to obtain this sample, the skin can be perforated, for example, on the fingertip or earlobe of the subject with a sterile, sharp lancet, thereby obtaining several microliters of blood for analysis. This method of sampling is particularly suitable for sample analysis carried out immediately after sample collection.

[0004] Especially in the so-called "Home-Monitorings", and therefore where medical practitioners themselves carry out simple blood or interstitial fluid analyzes and especially for regular diabetic blood collection carried out many times a day to control glucose levels blood, lancets and matching devices (so-called lancets) are offered. In particular, these lancets enable a medical practitioner to obtain as painless and reproducible a sample as possible. Such lancets and instrumentation are, for example, the subject of WO-A 98/48695, US 4,442,836 or US 5,554,166.

[0005] Determining blood sugar by hand, often carried out in private households, is today a widespread method in the control of diabetes worldwide. The prior art blood sugar measuring instruments consist of an analysis instrument into which a test element (test strip) is inserted. The test element contacts the droplet of the sample, which was briefly obtained previously with a lancing device, for example from a finger tip.

[0006] Numerous system components (lancet, lancing device, test element and analysis instrument) require a lot of space and entail relatively complex manipulation. Currently, however, there are systems with a higher degree of integration, and therefore simple manipulation, in which, for example, the test elements are stored in the instrument for analysis and are made available for measurement. The next stage of miniaturization is, for example, the integration of several functions or function elements in a single analytical aid (disposable). By the right combination of the puncturing process and sensory analysis on the test element, the operating process can be clearly simplified.

[0007] For example, it is known in the art to provide lancets of this type of analytical auxiliaries with a capillary structure or to make them as part of a capillary structure (see WO 2005/104948 A1, referring to this). In this case, the lancet blade is fed after puncturing and exiting the sample into the sample to collect the sample using a capillary.

EP 1 894 525 0001 [0008} The lancet blade for collecting blood or interstitial fluids is normally sterilized previously and kept sterile by a sterile protective element (e.g. in the form of a cap or pocket) before being used for the puncturing process. It is ensured that the lancet blade will not be contaminated by the surroundings. Remedial measures are also taken to ensure that the lancet blade is shielded after the puncture process (possibly through the same cap or pocket) so that inadvertent cuts and associated infections due to liquids sticking to the lancet blade are avoided.

[0009] For individual lancets, for example, a sterile protective element can be produced by spraying the lancet blade with plastic in one operation with the manufacture of the lancet body. Before use, the user removes this part manually, usually when placing the lancet in the lancing device. In the case of stored lancets, similar devices for sterile protection are commonly used, for example those in which the lancet is extended backwards from the sterile protective element, after which the sterile protective element is moved from the puncture path by spring force. To this end, relatively input mechanisms are needed, especially springs, integrated with the consumable material.

[0010] A number of packages for the medical auxiliaries described above are described in the prior art.

[0011] EP 1 360 935 A1 describes a tape pack for many medical aids. The auxiliary means are stored in the recesses of the first section of the tape, which are covered by the second section of the tape. To ensure the sterility of medical aids, they are sealed in flexible packaging material.

[0012] DE 28 03 345 B1 describes a blood sampling device with a needle moved by force against a patient's body surface. The needles are stored in the so-called tape packages with side-by-side pockets. The tape packaging is created from a base film and a top film of paper, plastic film or the like, with the base and top films stacked on top of each other and connected together in a ladder-shaped area to form pockets surrounding each side blood lancets.

[0013] Description WO 2004/075760 A1 relates to an automatically opening packaging for medical auxiliaries, comprising an upper flexible surface area having a distal end, a proximal end, a first peripheral edge and a second peripheral edge, an elastic round surface section having a distal end, a proximal end , first peripheral edge and second peripheral edge. In this case, the upper and lower elastic surface sections are capable of releasably welding together along at least one segment of their first and second peripheral edges, whereby the medical device is surrounded inside the upper and lower elastic surface sections. At the distal end of the upper flexible surface segment and at the distal end of the lower flexible surface segment a band is located, the band is located at the distal ends of the lower and upper flexible surface segment in such a way that the relative slipping movement of the band and the proximal ends of the upper and lower a flexible segment of the surface, reducing the distance between them, leads to the fact that it arises

EP 1 894 525 rozciąg1 extension of the upper and lower elastic surface segment. This automatically opens the packaging and reveals at least one section of the medical device.

[0014] Furthermore, WO 2005/104948 A1 discloses a test magazine with two sandwich-like films wound together, between which free receiving cells are held for the test elements, each comprising a puncture unit for puncturing into body tissue and testing unit for body fluid supply.

[0015] Lancets, and especially microneedles with capillaries are usually made of surgical steel, such as chromium alloy, stainless steel for low-carbon thermal improvement (material number 1.4021), which for the collection of blood and interstitial fluid by capillary forces may be a problem. The reason for this lies in the hydrophobicity of the steel, making it impossible to at least partially fill the capillary with capillary forces. However, to achieve almost or complete capillary filling, the capillary is usually hydrophilic coated, especially with a SiO layer₂, TiO₂, polyacrylic acid or dextran sulfate. Hydrophyte surfaces are high-energy, which leads to the fact that they reduce by absorption of gas molecules to their surface their surface energy successively, which in the case of absorption of polar compounds gradually leads to a loss of hydrophilicity of the coating. The state of the art described above does not provide guidance on ensuring the hydrophilicity of the surface of lancets, lancing devices and medical aids for as long as possible.

[0016] The object of the present invention is therefore to avoid the disadvantages of the prior art, and especially to provide packaging for hydrophilic objects, such as hydrophilic medical instruments, capillary microneedles, lancets and medical auxiliaries permanently ensuring the hydrophilicity of the object surrounded by the packaging.

[0017] This task is solved according to the invention by a plastic packaging with at least one receiving cell with at least one partially hydrophyte medical instrument for piercing into body tissue, having after radiation sterilization a proportion of volatile components ^ 0.1 pg / cm², preferably £ 0.01 pg / cm². Namely, it turned out that by reducing the amount of volatile components secreted by the packaging material to concentrations <0.1 pg / cm², you can ensure the lasting functionality of medical instruments equipped with a hydrophyte layer. By "stable" is meant in the present case that the hydrophilic coated medical instrument after at least about three months of storage in the package according to the invention has the same wetting properties as before its storage.

[0018] According to the invention, the term "plastic packaging" is understood to mean a plastic cover protecting the medical instrument wrapped in it against external contamination and lack of sterility. Thus, it is to ensure the possibly permanent sterility of the instrument. According to the invention, the packaging is made of plastic and therefore consists of 100% plastic. In one embodiment of the invention, the packaging includes plastic or a blend of plastics as packaging material in addition to further materials, such as, for example, metal foils. At the same time, the proportion of plastic may vary and

EP 1 894 525 Β1 can be varied within wide limits, for example in the range of 90 wt. : 10 wt. up to 10 wt. : 90 wt.

According to the invention, the term medical instrument is understood to be lancets, lancets, microneedles, particularly preferably micro-needles with capillary and uniformly functioning medical auxiliaries. Such medical instruments are preferably used to collect blood or interstitial fluids.

[0020] By "volatile components" is meant the components of the packaging that they successively release. The word "volatile" implies that substances belonging to the group of easily volatile components evaporate due to their high vapor pressure or relatively low boiling point. Volatile components are, for example, plasticizers such as phthalates. Volatile components can be characterized and quantified by Headspace gas chromatography.

[0021] According to the invention, the plastic package is a package surrounding a medical instrument, preferably a lancet for puncturing into body tissue. The medical instrument is selected from the group consisting of lancets, lancets, micro-needles, particularly preferably micro-needles with capillary and medical auxiliaries.

[0022] To improve the uptake of blood or interstitial fluids, the medical instruments previously described are at least partially hydrophilic and preferably at least segmentally provided with a hydrophilic coating. The staple hydrophilic coating is applied especially in places where the blood or interstitial fluid are in contact during sampling. By this, it is advantageously achieved that, for example, coated surgical steel capillaries almost or completely fill the test fluid.

[0023] In one embodiment of the invention, the packaging comprises polyester, in particular polyethylene terephthalate (PET) as packaging material in addition to further materials. In this case, the proportion of polyester can vary and can be varied within wide limits, for example in the range from 100: 1 to 1: 100. In a further embodiment, the packaging consists essentially of polyester, i.e., in addition to the polyester, one or more further materials may also be present, but only present in very small amounts below 1 wt. In a further embodiment, the packaging can be made of polyester and thus can be 100% polyester. [0024] Polyester is the name of polymers of general formula I or II.

Ϊ1

Ό — R— C— • O — R — O — C — R — C

I model 1 model 2 see regarding this Rómpp, Chemie Lexikon, Thieme Verlag Stuttgart, 10th extended edition, 1996, volume Pl-S, pages 3527 to 3528.

[0025] The polyesters are prepared by ring-opening reactions of lactones (I) or by polycondensation of hydroxycarboxylic acids (I) or diols and (derivatives) of carboxylic acid (II). Branched and cross-linked polyesters are obtained during tri4 polycondensation

EP 1 894 525 albo1 or polyvalent alcohols with multifunctional carboxylic acids. Polyesters also generally include polycarbonates (polyesters of carbonic acid).

[0026] Type I polyesters include, but are not limited to, polyglycolic acids, polylactic acids, polyhydroxybutyric acid, poly (e-caprolactone) and polyhydroxybenzoic acids.

[0027] Purely aliphatic type II polyesters are polycondensates of aliphatic diols and dicarboxylic acids, used among others as products with hydroxyl end groups as polydiols for the production of polyester urethanes. Type II polyesters with aliphatic diols and aromatic dicarboxylic acids are most important in quantity, especially polyalkylene terephthalate with polyethylene terephthalate (PET), polyethylene terephthalate (PBT), poly (1,4-cyclohexanedimethylene terephthalate) are the most important compounds.

[0028] Purely aromatic polyesters are polyarylates, which include, but are not limited to, poly (4-hydroxy-benzoic acid), bisphenol A and phosgene polycondensates.

[0029] In addition to the aforementioned polyesters, unsaturated polyesters can also be made from unsaturated dicarboxylic acids, which have gained technical significance as polyester resins, in particular as unsaturated polyester resins (UP resins). According to an embodiment of the invention, polyethylene terephthalate (PET) is preferred as a polyester.

[0030] The wall thickness of the plastic packaging is selected by a specialist depending on the item being packaged. According to one embodiment of the invention, the packaging has a wall thickness of 1 to 500 pm, preferably 20 to 80 pm, particularly preferably 30 pm. Due to the wall thickness in the above range, it is ensured that the packaging will not be damaged during storage or transport and will not become unsterile and permeable to bacteria and contaminants.

[0031] The wall of the plastic packaging according to the invention is preferably constructed in a single layer.

[0032] According to a further embodiment of the invention, the wall consists of a plurality of layers. Preferably, the packaging is characterized in this case in that the innermost layer essentially comprises polyester or consists of polyester. The advantage when using polyester as the wall material of the packaging according to the invention is that this polymer material also releases only a small proportion of easily volatile components, such as plasticizers, at temperatures around 60 °. The functionality of the instrument in the packaging is thus guaranteed for a long time, since only relatively small amounts of released components can settle on the hydrophobic coating of the instrument. A particularly preferred embodiment provides that the packaging further surrounds the test unit for supplying body fluid. According to a further embodiment of the invention, the medical instrument, preferably the lancing device and the testing unit are placed separately in separate receiving cells. For example, the cells can be made in a simple manner through the intermediate area between the non-formed films. The separation also achieves the advantage that the lancing device can be independently pretreated without damaging the testing chemicals, especially sterilized and hydrophilized, and that during the puncturing process there is no danger that the testing chemicals will enter the body.

EP 1 894 525 Według1 [0033] According to the invention, the medical instruments in the assigned receiving cells, formed by the packaging, are sterilized by irradiation, preferably through a mask to cover the testing units. Because the hydrophilic coatings are extremely sensitive, and in addition, for example, glucose test strips are packaged together with a medical instrument, they are taken as sterilization methods, particularly preferably radiation sterilization methods. The packaging, which serves as the packaging for the medical instrument, is therefore characterized in that it is sterilized by β or γ rays, particularly preferably by β rays.

[0034] According to the invention, suitable films for the packaging of hydrophilic coated medical instruments or instruments coated with hydrophilic layers can be preferably 30 pm thick films having a volatile component content of 0.1 pg / cm after sterilization with β rays², preferably s 0.01 pg / cm². Especially during comparative tests, polyester films - regardless of the manufacturer - showed very good results during gas chromatographic analysis of volatile components. So far, such films have been used mostly for food packaging.

[0035] The following examples and comparative examples explain the invention, but are not in any way intended to define or limit it.

[0036] List of drawings:

figure 1: capillary and associated assessment scheme for testing the packaging according to the invention figure 2: results of the storage test of hydrophilic SiO coated test plates₂ in two different packages.

[0037] An example of a capillary is shown in figure 1. The scale from 0 to 4 reflects the capillary filling properties. A value of 1 on this scale indicates poor capillary filling capacity, 4 very good filling capacity. Capillaries, characterized by a value of 4, allow the capillary to be almost or completely filled with blood or interstitial fluid.

[0038] To find out which films or materials are suitable for solving the problem of the invention, screening of the films was carried out. The volatile components of various films / bags were determined by means of Headspace gas chromatography. The corresponding results are mapped in Table 1 and show that polyester films with few additives have the smallest proportion of volatile components after β sterilization.

Table 1: Share of volatiles of various films. The marked values ​​give the thickness of each foil determined by means of a micrometer.

<td rowspan="2">Film / bag</td><td rowspan="2">Manufacturer</td><td rowspan="2">Thickness [pm]</td><td colspan="2">The share of volatile components [pg / cm²]</td>

<td>without treatment</td><td>after sterilization β</td>

<td>Melinex S. (polyester)</td><td>DuPont</td><td> 20*</td><td> &lt;0,01</td><td> 0,01</td>

<td>Hostaphan RN 23</td><td>Mitsubishi</td><td> 23</td><td> &lt;0,01</td><td> 0,01</td>

EP 1 894 525 Β1

<td>MED (polyester)</td><td colspan="4"></td>

<td>Hostaphan RN 19 (polyester)</td><td>Mitsubishi</td><td> 19</td><td> &lt;0,01</td><td> 0,01</td>

<td>Mylar 850 (polyester)</td><td>DuPont</td><td> 20</td><td> &lt;0,01</td><td> 0,01</td>

<td>Mylar 850 (polyester)</td><td>DuPont</td><td> 30</td><td> 0,01</td><td> 0,01</td>

<td>Mitsubishi RHS 12 (polyester)</td><td>Mitsubishi</td><td> 12</td><td> 0,01</td><td> 0,01</td>

<td>PA / PE</td><td>Medipack</td><td> 70*</td><td> 0,01</td><td> 0,02</td>

<td>Polialuvel polyester / alu / PE</td><td>Medipack</td><td> 90*</td><td> 0,01</td><td> 0,05</td>

<td>Teflon</td><td>DuPont</td><td> 50*</td><td> 0,01</td><td> 0,06</td>

<td>Hostaphan RHS thirty (polyester)</td><td>Mitsubishi</td><td> 30</td><td> 0,03</td><td> 0,06</td>

<td>Fruh 24093 (PA / PE)</td><td>Fruh</td><td> 90*</td><td> 0,03</td><td> 0,06</td>

<td>Alu / PE</td><td>Zewatener</td><td> 110*</td><td> 0,04</td><td> 0,01</td>

<td>Fruh 24086 (PA / PE)</td><td>Frtih</td><td> 90*</td><td> 0,16</td><td> 0,16</td>

<td>Topas 8007 F04</td><td>Ptitz Folien</td><td> 90</td><td> 0,06</td><td> 0,18</td>

<td>Barex (acrylonitrile)</td><td>Fruh</td><td> 50</td><td> 0,11</td><td> 0,31</td>

<td>Topas 8007 PE Blend (COC / PE)</td><td>Ptitz Folien</td><td> 70</td><td> 0,28</td><td> 0,41</td>

<td>Welded bag on the edges Polyester O / Alu / PE, 12-9-75</td><td>Sengewald Klinikprodukte</td><td> 96</td><td> 0,4</td><td></td>

[0039] An experiment was then carried out to determine the storage stability of the hydrophyte coating in two different films. 42 test plates, having capillaries, as seen in Fig. 1, were coated with a SiO hydrophyte layer₂. Then 21 of the test plates were packaged in Zewatener Alu / PE bags and 21 in DuPont polyester-containing Mylar bags. Then, the packed test plates were sterilized β (25 kgGy, 10 MeV) and stored for 12 weeks at 35 ° C. Two weeks apart, the plates were tested by pipetting 1.5 μl of blood onto the capillary area each time and assessing the filling properties of the respective capillary on the basis of the evaluation scheme shown in Figure 1. The results of the storage test are shown in figure 2. The figure shows the capillary filling properties (ranking from 1 to 4) relative to the storage time after sterilization in days. As can be seen from figure 2, the capillaries of the test plates

EP 1 894 525 Β1 packed in Mylar bags (share of volatile components: 0.01 pg / cm²) show optimum filling properties within 84 days, while the test plates packed in Alu / PE bags (volatile matter content: 0.06 pg / cm²) were getting worse with increasing storage time.

Therefore, it was possible to confirm experimentally by examination using gas chromatography discovered results.

[0040] The test using gas chromatography of volatile components was carried out as follows:

Tools, instrumentation and chemicals:

[0041]

Gas chromatograph: Carlo Erba HRGC 5300 with Head-Space, Autosampler in split mode or similar instrument

Kapilara: Chrompack Best.N. company 7761 or comparable capillary

Type: Wcot fused silica

Stationary phase: CPSIL 8 CB

Film thickness: 1.12 pm

id: 0.32 mm length: 25 m

Glassware and working tools:

[0042]

Test vessels: 10 ml HS glass

Chemicals:

[0043] toluene: Merck No. 1.09768.0005 carbon disulphide: Merck pa or chemicals of comparable quality No. 1.02214.1000

Partial test for volatile components (GC)

Standard:

[0044] 20-25 mg of toluene were considered exactly in a 50 ml 0.1 mg flask. 50 ml of carbon disulfide was added by pipette and weighed. About 10 mg of this solution was considered to 0.1 mg exactly into the HS glass and closed immediately.

EP 1 894 525 Β1 [0045] Two standard solutions are prepared and 3 HS glasses are considered from each standard solution. The volatile components are calculated using the average of all standards.

[0046] The standardization is at least one hour.

Sample preparation / reference quantity:

[0047] A 50 cm film fragment² of the tested sample is finely cut and fed into HS glass. At least one sample is prepared for each pattern.

Sample withdrawal time: 18 hours in the HS bath prior to analysis

Chromatographic conditions:

[0048]

Temperature program:

Initial U 40 C, 5 min Heating rate: 10 ° C / min "^" end · 280 ° C / 5 min

Partial volatility (GC) test plan

Heating zone temperature:

Mega 5300 [0049]

Injector: 250 ° C

Detector: 280 ° C

HS bath: 100 ° C. HS syringe: 100 ° C

Gas supply:

[0050]

Carrier gas: helium

Initial pressure: 0.5 bar

Fission: 1:40

Detector: instrument-specific settings

EP 1 894 525 Β1

FID Att .: 7

Multiplier: 1

Computer system: Chrome Card or comparable evaluation

Injection volume: 1.25 ml

Rating:

[0051] The assessment is carried out using an external standard method. The total area of ​​all volatiles is used to calculate and the amount is calculated using the toluene concentration and the toluene peak area. An average value is created from all results.