PHYSIOLOGICALLY ACTIVE PREPARATION COMPRISING N-ACETYL-GLUCOSAMINE FOR THE TREATMENT OF BACK PAIN

Abstract

A physiologically active composition for use in a method for the prophylaxis and/or treatment of back pain comprises N-acetyl-glucosamine or a suitable derivative of N-acetyl-glucosamine.

Claims

1-10. (canceled)

11. A physiologically active composition comprising N-acetyl-glucosamine or a derivative of N-acetyl-glucosamine for use in a method for the prophylaxis and/or treatment of back pain.

12. The composition according to claim 11, further comprising silica.

13. The composition according to claim 12, wherein the silica is provided in the form of a constituent of a bamboo extract.

14. The composition according to claim 11, further comprising collagen.

15. The composition according to claim 14, wherein the collagen is provided in the form of a constituent of a collagen hydrolysate.

16. The composition according to claim 11, further comprising hyaluronic acid.

17. The composition according to claim 16, wherein the hyaluronic acid is provided in the form of a constituent of a collagen hydrolysate.

18. The composition according to claim 11, further comprising at least one of lysine and vitamin C.

19. A physiologically active composition which comprises at least two components, of which a first component is silica and a second component is N-acetyl-glucosamine or a derivative of N-acetyl-glucosamine.

20. The composition according to claim 19, wherein silica is provided in the form of a constituent of a bamboo extract.

21. The composition according to claim 19, further comprising at least one of collagen, hyaluronic acid, lysine and vitamin C.

22. The composition according to claim 11 in the form of an oral dosage form.

23. The composition according to claim 19 in the form of an oral dosage form.

24. A nutritional supplement comprising the composition as in claim 11.

25. A nutritional supplement comprising the composition as in claim 19.

26. A method for the prophylaxis and/or treatment of back pain, comprising: administering a physiologically active composition comprising N-acetyl-glucosamine or a derivative of N-acetyl-glucosamine.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0061] An exemplary embodiment of the solution according to the invention will be explained in greater detail hereinbelow with reference to the accompanying drawing, in which:

[0062] FIG. 1 is a schematic overview of an exemplary embodiment of a physiologically active composition according to the invention.

[0063] FIG. 2 is a schematic overview of a method for the production of the exemplary embodiment according to FIG. 1.

[0064] FIG. 3 is a schematic overview of a method for the production of N-acetyl-glucosamine for the exemplary embodiment according to FIG. 1.

DETAILED DESCRIPTION

[0065] FIG. 1 illustrates a physiologically active composition 10, as is contained in a capsule 11 as an oral dosage form. The capsule 11 serves as a nutritional supplement for maintaining and building up the intervertebral disc.

[0066] To that end, the capsule 11 has a transparent and hard capsule casing 12 of hydroxypropylmethylcellulose. Inside the capsule casing 12 is the composition 10 in the form of an active ingredient mixture of several components.

[0067] A first component of the composition 10 is silica 13, which is present in the form of natural silicon dioxide in an amount by mass of 75 percent by weight in the form of a constituent of a bamboo extract 14. The bamboo extract 14 is further present in an amount of 70.0 milligrams in the capsule casing, which gives 52.5 milligrams of natural silicon dioxide as the silica 13. A residual amount 16 of the bamboo extract 14, with 17.5 milligrams, amounts to 25 percent by weight, based on the bamboo extract 14, and comprises calcium, choline and betaine.

[0068] A second component of the composition 10 is N-acetyl-glucosamine 18, or N-acetyl-D-glucosamine, in an amount of 100.0 milligrams. The bamboo extract 14 is thus present in a mass ratio of 0.7 in relation to N-acetyl-glucosamine 18.

[0069] The composition 10 further includes collagen hydrolysate 20 in an amount of 300.0 milligrams. The collagen hydrolysate 20 comprises as a further component collagen 22 in an amount by mass of from 60 to 70 percent by weight, in the present case 60 percent by weight in an amount of 180 milligrams. Collagen 22 is hydrolysed and is preferably in the form of type II collagen.

[0070] The collagen hydrolysate 20 additionally comprises as a further component approximately 30 percent by weight mucopolysaccharides or glycosaminoglycans 24 in an amount of approximately 90.0 milligrams. There are further provided in the collagen hydrolysate 20 approximately 10 percent by weight hyaluronic acid 26 in an amount of approximately 30 milligrams as an additional further component of the composition 10.

[0071] In total, the collagen hydrolysate 20 has a mass ratio relative to N-acetyl-glucosamine 18 of 3.0.

[0072] In addition, lysine 28 is present in a stabilised form as L-lysine hydrochloride in an amount of 35.0 milligrams as a further component of the composition 10. The amount of L-lysine hydrochloride of 35.0 milligrams gives an effective amount of L-lysine of 28.0 milligrams. Lysine 28 thus has a mass ratio of 0.28 relative to N-acetyl-glucosamine 18.

[0073] As a further component the composition 10 comprises L-(+)-ascorbic acid, or ascorbic acid, as vitamin C 30 in an amount of 37.5 milligrams. A stability supplement of 25 percent by weight is included therein, in order to compensate for a loss of vitamin C 30 that occurs on prolonged storage. A mass ratio of vitamin C 30 to N-acetyl-glucosamine 18 is approximately between 0.38 and 0.30, depending on the loss on storage.

[0074] There are further present in the composition 10 19.5 milligrams of magnesium stearate 32 of vegetable origin as an auxiliary agent.

[0075] With 100.0 milligrams of N-acetyl-D-glucosamine 18 of the composition 10 per capsule 11, a particularly effective dose can be achieved with an intake of four capsules 11 per day.

[0076] For a particularly good effect, in particular in the case of acute pain, the capsules 11 should be taken in an amount of two times two capsules 11 per day over a period of from two to four weeks. Uptake of the components as active ingredients or nutrients in the body is thus achieved. Thereafter, the intake can be reduced to two capsules 11 per day, divided into two times one capsule 11, for a period of eight weeks. Preference is given to a duration of intake of twelve weeks. The capsules should be taken with copious amounts of liquid after eating.

[0077] FIG. 2 shows a production method for the capsule 11. The bamboo extract 14, N-acetyl-glucosamine 18, collagen hydrolysate 20, lysine 28 and vitamin C 30 as active ingredient components and magnesium stearate 32 as auxiliary agent are thereby mixed in a step 34 at an ambient temperature of approximately 20 C. Thereafter, in a step 36, encapsulation of the mixed composition 10 so obtained into an empty capsule casing 13 is carried out at 20 C. The capsule 11 is obtained.

[0078] FIG. 3 shows two fundamentally different methods 38 and 40 for producing the active ingredient N-acetyl-D-glucosamine 18. In both cases, natural chitin 42 is used as starting material.

[0079] Chitin 42 is a polysaccharide which consists throughout of -1,4-glycosidically linked N-acetyl-glucosamine molecules. Chitin 42 is thus particularly suitable for obtaining N-acetyl-glucosamine 18. In both methods 38 and 40, chitin 42 from shells of crustaceans is used.

[0080] One method 48 is a partially synthetic method, in which natural chitin 42 is subjected to a step 44 of acid hydrolysis, or cleavage. Chitin 42 is thereby cleaved into its individual structural components by means of a strong acid 46. The acid 46 additionally effects cleavage of the acetyl group from the nitrogen of the N-acetyl-glucosamine 18.

[0081] In a first variant for the present exemplary embodiment, concentrated hydrochloric acid is used as the acid 46. Glucosamine hydrochloride is thus formed as an intermediate product 48 in the step 44 of acid hydrolysis, and is subsequently concentrated, crystallised and purified. The intermediate product 48 glucosamine hydrochloride so obtained is dissolved in water and reacted with acetic anhydride 50 in a step 52 of re-acetylation to N-acetyl-glucosamine 18. After crystallisation and purification by means of ethanol, N-acetyl-glucosamine 18 is obtained in a purity of 97.5 percent.

[0082] In an alternative variant, sulfuric acid is used instead of hydrochloric acid as the strong acid 46 in the method 38, which leads to glucosamine sulfate as the intermediate product 48.

[0083] In a further alternative variant, N-acetyl-glucosamine 18 is obtained by means of the other method 40 directly from a cleavage of natural chitin 42. To that end, chitin 42 is swelled with phosphoric acid and then neutralised and subjected in a step 54 to enzymatic hydrolysis by means of an enzyme 56. The enzyme 56 is chitinase. When the hydrolysis is complete, and after subsequent filtration and crystallisation, N-acetyl-glucosamine 18 of completely natural origin is available particularly purely, quickly and simply.

[0084] A prospective study which is currently ongoing is described hereinbelow, the interim results of which already demonstrate the activity of the physiologically active composition 10.

[0085] In the study, in particular the effects of an administration of the composition 10 to patients with lumbar osteochondrosis, or lumbar vertebral osteochondrosis, are studied.

[0086] Such lumbar osteochondrosis is generally observed as a degeneration of the intervertebral disc, which contributes to pain, loss of function of the lower back and absence from work. This problem is to be observed especially in the industrialised world. There is still little understanding of the primary cause of lumbar osteochondrosis. Multi-factorial aspects, such as hereditary, anatomical, traumatic, nutritional, inflammatory and metabolic factors, are probably involved in the progression of the disease.

[0087] In addition to a surgical intervention, which is often undesirable, there are various non-surgical therapies for lumbar osteochondrosis, with which pain is to be reduced and normal functions can be regained. Such non-surgical therapies are pharmaceutical pain therapies with, for example, analgesics, non-steroidal anti-inflammatory medicaments, muscle relaxants and/or opiates. Also included are physical therapies, such as, for example, physiotherapy, electrotherapy, ultrasound and/or heat treatment. In addition, treatment with injections is known, such as, for example, trigger point injections and injections to release nerve blocks. Appropriate nutrition alone probably cannot prevent lumbar osteochondrosis, while nutrition management could delay its progression.

[0088] In general, nutritional supplements are used for nutrition management and offered anecdotally in clinical practice, despite often contradictory statements and scientific explanations regarding the effectiveness of the individual substances. Moreover, dietetic measures pose a low health risk, so that there are scarcely any studies which have investigated such non-surgical treatment possibilities.

[0089] Accordingly, the still ongoing study was begun, which is a prospective, double-blind for patient and investigator, placebo-controlled, 1:1 randomised study of the adjuvant treatment of lumbar osteochondrosis.

[0090] The study is to evaluate the effectiveness of the composition 10 as a nutritional supplement in the treatment of lumbar osteochondrosis.

[0091] To that end, the composition 10 is used as a nutritional supplement. It bears the trade name vertebene. The composition 10, with its combination of ingredients, or nutrients, contains substances which occur naturally in the intervertebral disc, such as, for example, collagen fibres and proteoglycans, such as aggrecan. Such a composition 10 should contribute towards improving back pain and/or at least maintaining vertebral column function.

[0092] The two primary aims of the study are firstly to evaluate pain and function of the vertebral column and secondly to measure the distance between two vertebral bodies by means of magnetic resonance tomography (MRT), before and after supplementation with the composition 10.

[0093] For the study, patients are chosen who go to see an orthopaedic specialist because of lumbar osteochondrosis.

[0094] The chosen patients are allocated at random either to a nutritional supplement group, or verum group, or to a placebo group in the ratio 1:1.

[0095] The study is a double-blind study, in which neither the patients nor the investigator know who is receiving which test preparation. The test preparations are the composition 10 as the verum, or active substance, and a control preparation as the placebo. Such blinding must not be broken in the course of the ongoing study but only on conclusion of the study, that is to say when the last patient is finished.

[0096] Supplementation is carried out for an intervention period of three months. To that end, the patients of both groups take per day two times two capsules of the composition 10 or of the placebo. In addition, the patients are instructed to carry out specific physical exercises.

[0097] Data listed hereinbelow are acquired and collected at the beginning of the study, prior to supplementation, as the starting value and after supplementation.

[0098] Pain and function are assessed according to subjective patient questionnaires. These include a questionnaire according to the Oswestry Disability Index (ODI), in which the patients evaluate the limitations they experience in different functional areas including pain intensity. As further subjective parameters, pain is assessed according to the visual analogue scale (VAS) and quality of life is assessed according to the short form 12 (SF-12) questionnaire. Questions are asked about dietary habits according to the food frequency questionnaire (FFQ) and about physical activity according to the Global Physical Activity Questionnaire (GPAQ) of the World Health Organisation (WHO). In addition, a general assessment of the effectiveness of, or satisfaction with, the nutritional supplement is made.

[0099] Within the scope of clinical and radiological examinations, the distance between two vertebral bodies, the structure and height of the vertebral bodies and the bone marrow structure are measured by means of magnetic resonance tomography (MRT). In addition, an X-ray examination is carried out in order to determine the distance between two vertebral bodies and to evaluate the osteochondrosis.

[0100] A blood sample is additionally taken. Nutritional and inflammation blood parameters and blood parameters relating to oxidative stress are thereby determined. A reverse transcriptase polymerase chain reaction (RT-PCR) for the expression of chondrogenic genes is also carried out.

[0101] Since the study is currently not complete, the blinding has consequently also not yet been broken. Despite such a data situation, a current interim state shows the following, promising interim results.

[0102] Of the planned 100 patients (50 verum, 50 placebo), 20 patients have so far been recruited. Of these, twelve patients have been included in the study. Ten of these twelve patients have completed the three-month intervention.

[0103] Of these ten patients, six patients showed an improvement in symptoms, in two patients the result stayed the same, and in a further two patients there was a slight worsening of the symptoms. The worsening could be due to administration of the placebo.

[0104] Analysis of the MRT images also showed very similar results. In 50 percent of the patients, the condition has improved by one degree relative to the starting point. In 30 percent of the patients, the condition has remained the same. In 20 percent, the condition has become worse compared to the starting point, which again could be due to administration of the placebo.

[0105] A comparison between verum and placebo is not yet possible because the blinding has not been broken. However, these interim results already give very clear evidence that, by means of an intake of the composition 10, an improvement in symptoms can be achieved at least in the case of lumbar osteochondrosis.

[0106] The composition 10, in particular after completion of the study and further positive results, can be offered as an adjuvant therapy for the prophylaxis and/or treatment of back pain, in particular in the case of degenerative vertebral column pain, or intervertebral disc pain, such as lumbar osteochondrosis.

[0107] Finally, it should be noted that all the features which are mentioned in the application documents and in particular in the dependent claims are to be accorded independent protection, also individually or in any desired combination, despite the formal dependence on one or more specific claims which has been made.

LIST OF REFERENCE NUMERALS

[0108] 10 composition [0109] 11 capsule [0110] 12 capsule casing [0111] 13 silica [0112] 14 bamboo extract [0113] 16 residual portion bamboo extract [0114] 18 N-acetyl-glucosamine [0115] 20 collagen hydrolysate [0116] 22 collagen [0117] 24 mucopolysaccharides or glycosaminoglycans [0118] 26 hyaluronic acid [0119] 28 lysine [0120] 30 vitamin C [0121] 32 magnesium stearate [0122] 34 mixing step [0123] 36 encapsulation step [0124] 38 method for producing N-acetyl-glucosamine [0125] 40 method for producing N-acetyl-glucosamine [0126] 42 chitin [0127] 44 acid hydrolysis step [0128] 46 strong acid [0129] 48 intermediate product [0130] 50 acetic anhydride [0131] 52 re-acetylation step [0132] 54 enzymatic hydrolysis step [0133] 56 enzyme