In-vitro diagnostic medical devices for determining saliva volume

Abstract

The invention relates to a method of collecting saliva from the oral cavity for detecting a test substance, comprising the steps of (a) cleaning the oral cavity, (b) stimulating saliva secretion with a saliva-collecting solution, (c) removing the saliva-saliva collecting solution mixture from the oral cavity and collecting it in a container ( 1 ), (d) transferring the saliva-saliva collecting solution mixture into a sealable collection vessel.

1 . Method of collecting saliva from the oral cavity in order to detect a test substance, comprising the steps of (a) cleaning the oral cavity, (b) stimulating saliva secretion with a saliva-collecting solution, (c) removing the saliva-saliva collecting solution mixture from the oral cavity and collecting it in a container ( 1 ), (d) transferring the saliva-saliva collecting solution mixture to a sealable collection vessel.  
   
   
       2 . Method according to  claim 1 , wherein the secretion of saliva is increased by the saliva-collecting solution with taste-stimulating properties.  
   
   
       3 . Method according to  claim 1 , wherein the saliva-saliva collecting solution mixture is transferred via a transfer mechanism ( 7 ) integrated in or on the container ( 1 ) into the sealable collection vessel.  
   
   
       4 . Method according to  claim 1 , wherein particulate elements are removed from the saliva-saliva collecting solution mixture by means of a filtration unit ( 13 ) in the container ( 1 ).  
   
   
       5 . Method according to  claim 1 , wherein a sealable collection vessel is used with a solution having preserving and reducing properties.  
   
   
       6 . Method according to  claim 1 , wherein the quantity of saliva is quantitatively determined.  
   
   
       7 . Method according to  claim 1 , wherein the saliva is quantified using at least one calibrator solution.  
   
   
       8 . Method according to  claim 1 , wherein in order to make a quantitative determination, the concentration and/or extinction of the indicator substance and/or reagent of the saliva-saliva collecting solution mixture is compared with the concentration and/or extinction of the indicator substance and/or reagent present in the saliva prior to taking the sample.  
   
   
       9 . Method according to  claim 1 , wherein the saliva-saliva collecting solution mixture present in the evacuated collection vessel is centrifuged and optionally mixed beforehand.  
   
   
       10 . Method according to  claim 1 , wherein the saliva-saliva collecting solution mixture is used for conducting tests.  
   
   
       11 . Method according to  claim 1 , wherein the tests are conducted in standardised laboratory measuring equipment.  
   
   
       12 . Saliva-collecting solution for obtaining saliva, wherein a composition is based on a substance with taste-stimulating properties, an indicator substance and/or reagent and water.  
   
   
       13 . Saliva-collecting solution according to  claim 12 , wherein the substance with taste-stimulating properties is selected from a group of inorganic and/or organic edible acids and/or salts or mixtures thereof.  
   
   
       14 . Saliva-collecting solution according to  claim 13 , wherein the edible acids are selected from a group comprising phosphoric acid, lactic acid, citric acid, ascorbic acid.  
   
   
       15 . Saliva-collecting solution according to  claim 12 , wherein the substance with taste-stimulating properties is an active substance such as pilocarpin, for example.  
   
   
       16 . Saliva-collecting solution according to  claim 12 , wherein the concentration of the substance with taste-stimulating properties is selected so as to be within a range with a lower limit of 0.0005%, in particular 0.01% preferably 1%, and an upper limit of 10% in particular 5%, preferably 2%.  
   
   
       17 . Saliva-collecting solution according to  claim 12 , wherein it contains a dye as the indicator substance.  
   
   
       18 . Saliva-collecting solution according to  claim 17 , wherein the dye is water-soluble.  
   
   
       19 . Saliva-collecting solution according to  claim 12 , wherein the dye causes a yellow colouration and is selected from a group comprising tartrazine, curcumin, saffron, quinoline yellow, sunset yellow FCF, yellow orange 5, cochineal, carminic acid, carmine, carotene, or mixtures thereof  
   
   
       20 . Saliva-collecting solution according to  claim 12 , wherein a dye is selected from a group comprising riboflavin, riboflavin-5′-phosphate, chlorophyl and chlorphylline, copper-containing complexes of chlorophyls and chlorophyllines, sugar-based caramel dye, simple caramel dye, sulphite lye-caramel dye, ammonia-caramel dye, ammonium sulphite-caramel dye, vegetable carbons, paprika extract, capsanthin, capsorubin, beetroot, betanin, antho-cyans, iron oxides and hydroxides, azorubin, carmoisin, Ponceau 4R, cochineal red A, allura red AC, patent blue V, indigotin, indigo carmine, brilliant blue FCF, green S, brilliant black BN, black PN, brown HT, lycopene, Beta-apo-8′-Carotinal (C 30), Beta-apo-8′-carotinic acid (C 30)-ethyl ester, lutein, substances of Maillard compounds and/or mixtures thereof.  
   
   
       21 . Saliva-collecting solution according to  claim 12 , wherein the concentration of dye is selected from a range with a lower limit of 0.0001% in particular 0.005%, preferably 0.1%, and an upper limit of 5%, in particular 1%, preferably 0.5%.  
   
   
       22 . Saliva-collecting solution according to  claim 12 , wherein a reagent in the sense of a medicinal product, in-vitro diagnostic medical devices and/or pharmaceutical product is added.  
   
   
       23 . Saliva-collecting solution according to  claim 12 , wherein a quantity of a reagent which can be detected by laboratory measuring equipment used as a matter of routine is added.  
   
   
       24 . Saliva-collecting solution according to  claim 23 , wherein the added reagent is a representative selected from a group comprising bilirubin, acetaminophen, acidic phosphatase, albumin, creatinin, alcohol, alkaline phosphatase, alaninamino-transferase, ammonia, amylase, aspartatamino-transferase, bilirubin, unconjugated and conjugated, urea, calcium, bicarbonate, cholinesterase, LDL- or HDL cholesterine, lysozyme, amylase, creatin kinase, creatin kinase—MB, chloride, carbamazepin, creatinin, c-reactive protein, direct bilirubin, digoxin, carbon dioxide, iron, gamma-glutamyl transferase, glucose, magnetic HDL-cholesterine reagent, potassium, lactate, lactate dehydrogenase, lithium, lipase, inorganic compounds, such as for example trace elements, minerals, such as magnesium, sodium, new-born bilirubin, phenobarbital, phosphorous, phenytom, primidon, liquor protein, salicylate, whole bilirubin, theophylline, reagent for whole iron binding capacity, whole protein, triglyceride, urine protein, uric acid, β-microglobulin, corticosteroid- or sex hormone-binding globulin, thiocyanate, transferrin, various lipids, lipoproteins, proteins, carbohydrates, in particular water-soluble carbohydrates, vitamins, in particular water-soluble vitamins, such as for example vitamins of the B, C and F group, inorganic compounds, such as for example trace elements, minerals, hormones, such as for example aldosterone, androstenedion, cortisone, dihydroepiandrosterone, or -sulphates, oestradiol, oestriol, progesterone, testosterone, or mixtures thereof.  
   
   
       25 . Saliva-collecting solution according to  claim 12 , wherein the concentration of the reagent is selected from a range with a lower limit of 0.0000000001%, in particular 0.00005% preferably 0.001% and an upper limit of 10%, in particular 5%, preferably 2%.  
   
   
       26 . Saliva-collecting solution according to  claim 12 , wherein a flavouring and/or flavour enhancer is added.  
   
   
       27 . Saliva-collecting solution according to  claim 26 , wherein the flavouring is selected from a group of sugar types or sugar substitutes, such as for example saccharose, maltose, fructose, and/or sweeteners, such as for example saccharin, aspartam, and/or mixtures thereof.  
   
   
       28 . Saliva-collecting solution according to  claim 26 , wherein the flavouring or flavour enhancer may be of natural and/or synthetic origin and is selected from a group comprising fruits, such as apples, raspberries, cherries, strawberries, lemon, lime, orange, liquorice, herbs, quinine, caffeine, tannin, or mixtures thereof.  
   
   
       29 . Saliva-collecting solution according to  claim 26 , wherein the concentration of flavouring and/or flavour enhancer is selected from a range with a lower limit of 0.001(%), in particular 0.01%, preferably 0.1%, and an upper limit of 10%, in particular 5%, preferably 1%.  
   
   
       30 . Saliva-collecting solution according to  claim 12 , wherein the pH value is selected from a range with a lower limit of 3, preferably 3.5, in particular 4 and an upper limit of 6, preferably 5, in particular 4.5.  
   
   
       31 . Container ( 1 ) for biological fluids consisting of a base part ( 2 ) and a cover part ( 3 ), each with an external ( 5 ) and internal face ( 4 ), a cut-out ( 6 ) in the form of a recess being provided in the cover part ( 3 ) in which a transfer mechanism ( 7 ) comprising a device for penetrating ( 8 ) a collection vessel on the external face ( 5 ) of the cover part ( 3 ) and a projection ( 9 ) with two ends ( 10 ,  11 ) on the internal face ( 4 ) of the cover part ( 3 ) is disposed, wherein when the container ( 1 ) is in the assembled state, the end ( 11 ) lying closer to the base part ( 2 ) is at a distance ( 12 ) of 3 mm maximum from the base part ( 2 ).  
   
   
       32 . Container ( 1 ) according to  claim 31 , wherein the distance ( 12 ) from the base part ( 2 ) is selected from a range with a lower limit of 0.1 mm, in particular 0.5 mm, preferably 1 mm, and an upper limit of 3 mm, in particular 2 mm, preferably 1.5 mm.  
   
   
       33 . Container ( 1 ) according to  claim 31 , wherein a filtration unit ( 13 ) is disposed upstream of or in the transfer mechanism ( 7 ).  
   
   
       34 . Container ( 1 ) according to  claim 33 , wherein the filtration unit ( 13 ) is made from a material selected from a group comprising glass wool, cotton wool, filter paper, foam rubber, regenerated cellulose, cellulose triacetate, nylon, nitrocellulose, polyvinyldifluoride (PVDF), PVP, polyether sulphonate.  
   
   
       35 . Container ( 1 ) according to  claim 33 , wherein the filtration unit ( 13 ) is provided in the form of a membrane.  
   
   
       36 . Container ( 1 ) according to  claim 33 , wherein the filtration unit ( 13 ) has a pore size selected from a range with a lower limit of 1 μm, in particular 10 μm, preferably 20 μm, and an upper limit of 100 μm, in particular 60 μm preferably 50 μm.  
   
   
       37 . Sealable collection vessel for accommodating biological fluids, such as for example blood, with an internal face directed towards a biological sample, wherein it contains a solution with a stabiliser or preservative and a reagent for dissolving the biological fluid or elements thereof.  
   
   
       38 . Collection vessel according to  claim 37 , wherein the stabiliser or preservative is potassium benzoate, potassium sorbate, sodium azide and/or Thimerosal®.  
   
   
       39 . Collection vessel according to  claim 38 , wherein the concentration of potassium benzoate or potassium sorbate is selected from a range with a lower limit of 0.05%, in particular 0.1%, preferably 1%, and an upper limit of 10%, in particular 5%, preferably 2%.  
   
   
       40 . Collection vessel according to  claim 38 , wherein the concentration of sodium azide or Thimerosal® is selected from a range with a lower limit of 0.005%, in particular 0.01%, preferably 0.1%, and an upper limit of 1%, in particular 0.5%, preferably 0.2%.  
   
   
       41 . Collection vessel according to  claim 37 , wherein the dissolving reagent is ammonium sulphate, sodium chloride and/or potassium chloride.  
   
   
       42 . Collection vessel according to  claim 41 , wherein the concentration of the dissolving reagent is selected from a range with a lower limit of 0.005%, in particular 0.01%, preferably 0.1%, and an upper limit of 5%, in particular 1%, preferably 0.5%.  
   
   
       43 . Collection vessel according to  claim 37 , wherein the volume of the solution is selected from a range with a lower limit of 5 μl, in particular 20 μl, preferably 30 μl, and an upper limit of 500 μl, in particular 100 μl, preferably 50 μl.  
   
   
       44 . Collection vessel according to  claim 37 , wherein the internal face of the collection vessel is sprayed with the solution and the internal face is optionally dried.  
   
   
       45 . Collection vessel according to  claim 37 , wherein it is evacuated.  
   
   
       46 . Saliva imitation solution for imitating the composition of physiological saliva, wherein it contains sodium, potassium or calcium compounds, human serum albumin, urea and water.  
   
   
       47 . Saliva imitation solution according to  claim 46 , wherein the concentration of the sodium, potassium or calcium compounds is selected from a range with a lower limit of 0.001%, in particular 0.01%, preferably 0.1%, and an upper limit of 20% in particular 10%, preferably 5%.  
   
   
       48 . Saliva imitation solution according to  claim 46 , wherein the concentration of human serum albumin is selected from a range with a lower limit of 0.001%, in particular 0.01%, preferably 0.1%, and an upper limit of 5%, in particular 2.5%, preferably 1%.  
   
   
       49 . Saliva imitation solution according to  claim 46 , wherein the concentration of urea is selected from a range with a lower limit of 0.0005%, in particular 0.001%, preferably 0.01%, and an upper limit of 2%, in particular 1%, preferably 0.5%.  
   
   
       50 . Saliva imitation solution according to  claim 46 , wherein it contains lactoferrin.  
   
   
       51 . Saliva imitation solution according to  claim 50 , wherein the concentration of lactoferrin is selected from a range with a lower limit of 0.000001%, in particular 0.00001%, preferably 0.0001%, and an upper limit of 0.1%, in particular 0.01%, preferably 0.005%.  
   
   
       52 . Saliva imitation solution according to  claim 46 , wherein it contains gelatine.  
   
   
       53 . Saliva imitation solution according to  claim 52 , wherein the concentration of gelatine is selected from a range with a lower limit of 0.005%, in particular 0.01%, preferably 0.1%, and an upper limit of 5%, in particular 1%, preferably 0.5%.  
   
   
       54 . Saliva imitation solution according to  claim 46 , wherein the pH value is selected from a range with a lower limit of 5, preferably 5.5, in particular 6 and an upper limit of 7.5, preferably 7, in particular 6.5.  
   
   
       55 . Calibrator solution for quantifying the saliva volume, wherein it contains a saliva-collecting solution and/or a saliva imitation solution and sodium azide, potassium benzoate, potassium sorbate and/or Thimerosal®.  
   
   
       56 . Calibrator solution as claimed in  claim 55 , wherein it contains the saliva-collecting solution and the saliva imitation solution in an approximately inversely proportional ratio.  
   
   
       57 . Calibrator solution according to  claim 55 , wherein it contains the saliva-collecting solution and the saliva imitation solution respectively in a volume based on a gradient.  
   
   
       58 . Calibrator solution according to  claim 55 , wherein the concentration of sodium azide, potassium benzoate, potassium sorbate and/or Thimerosal® is selected from a range with a lower limit of 0.005%, in particular 0.01%, preferably 0.1%, and an upper limit of 5%, in particular 1%, preferably 0.5%.  
   
   
       59 . Test kit for obtaining saliva, wherein it contains a saliva-collecting solution according and a container ( 1 ) according to  claim 31 .  
   
   
       60 . Test kit according to  claim 59 , wherein it contains at least one sealable collection vessel.  
   
   
       61 . Test kit according to  claim 59 , wherein it contains at least one saliva imitation solution and at least one calibrator solution.  
   
   
       62 . Test kit according to  claim 59 , wherein it contains at least one microtitre plate, test tube and/or instructions for use.