1. A network management system NMS node for re-configuring a set of data network nodes in a data network in response to a change management request requesting a creation of a network service to be performed in the data network, the network management system node being characterised in that it comprises a processing unit configured to:
store each change of network service information in created, added andor updated data network nodes in the resulting set of data network nodes established by the re-configuration of the set of data network nodes based on the change management request requesting the creation of the network service as a change-set of network service information (X), and
associate the change-set of network service information (X) with a network service instance indicating the moment of the creation of the network service.
2. A network management system node according to claim 1, wherein, in response to the change management request, the processing unit is further configured to:
enable a transaction operation operable to cause the creation of the network service by re-configuring the set of data network nodes into the resulting set of data network nodes based on the change management request requesting the creation of the network service, and
commit the transaction operation to the data network in order to instantiate and mutually configure the resulting set of data network nodes in the data network.
3. A network management system node according to claim 1, wherein the processing unit is further configured to retrieve and use the stored change-set of network service information (X) in subsequent re-configurations of the resulting set of data network nodes based on subsequent change management requests.
4. A network management system node according to claim 3, wherein, in response to a subsequent change management request requesting a modification of an existing network service being performed by at least one of the data network nodes in the resulting set of data network nodes, the processing unit is configured to:
enable a transaction operation operable to cause the modification of the network service by:
deleting each change of network service information in created, added andor updated data network nodes in the change-set of network service information (X) associated with the network service instance corresponding to the creation of the network service that is to be modified,
re-configuring the remaining set of data network nodes into a modified set of data network nodes based on the change management request requesting the modification of the network service,
storing each change of network service information in created, added andor updated data network nodes in the modified set of data network nodes as the change-set of network service information (X),
associating the change-set of network service information (X) with a network service instance indicating the moment of the modification of the network service, and
commit the transaction operation to the data network in order to instantiate and mutually configure the modified set of data network nodes in the data network.
5. A network management system node according to claim 3, wherein, in response to a subsequent change management request requesting a deletion of an existing network service being performed by at least one of the data network nodes in the resulting set of data network nodes, the processing unit is configured to:
enable a transaction operation operable to cause the deletion of the network service by deleting each change of network service information in created, added andor updated data network nodes in the change-set of network service information (X) associated with the network service instance corresponding to the creation of the network service that is to be deleted, and
commit the transaction operation to the data network in order to instantiate and mutually configure the set in the data network.
6. A network management system node according to claim 1, wherein the change management request is based on a data model describing the network service in the data network and is mapped to corresponding network service information in one or more data network nodes in the data network for implementing the network service.
7. A network management system node according to claim 1, wherein the data network is a website server network and the data network nodes comprises a load balancing node and at least one webserver.
8. A network management system node according to claim 1, wherein the data network is MPLS-VPN network and the data network nodes comprises at least one customer edge node, and at least one provider edge node.
9. A website server network comprising a network management system node according to claim 1.
10. A MPLS-VPN network comprising a network management system node according to claim 1.
11. A method for use in a network management system NMS node for re-configuring a set of data network nodes in a data network, comprising:
receiving a change management request requesting a creation of a network service to be performed in the data network;
said method being characterised by comprising:
storing each change of network service information in created, added andor updated data network nodes in the resulting set of data network nodes established by the re-configuration of the set of data network nodes based on the change management request requesting the creation of the network service as a change-set of network service information (X); and
associating the change-set of network service information (X) with a network service instance indicating the moment of the creation of the network service.
12. A method according to claim 11, further comprising:
enabling a transaction operation operable to cause the creation of the network service by re-configuring the set of data network nodes into the resulting set of data network nodes based on the change management request requesting the creation of the network service; and
committing the transaction operation to the data network in order to instantiate and mutually configure the resulting set of data network nodes in the data network.
13. A method according to claim 11, further comprising:
receiving a subsequent change management request requesting a modification of an existing network service being performed by at least one of the data network nodes in the resulting set of data network nodes;
enabling a transaction operation operable to cause the modification of the network service by:
deleting each change of network service information in created, added andor updated data network nodes in the change-set of network service information (X) associated with the network service instance corresponding to the creation of the network service that is to be modified,
re-configuring the remaining set of data network nodes into a modified set of data network nodes based on the change management request requesting the modification of the network service,
storing each change of network service information in created, added andor updated data network nodes in the modified set of data network nodes as the change-set of network service information (X),
associating the change-set of network service information (X) with a network service instance indicating the moment of the modification of the network service; and
committing the transaction operation to the data network in order to instantiate and mutually configure the modified set of data network nodes in the data network.
14. A method according to claim 11, further comprising:
receiving a subsequent change management request requesting a deletion of an existing network service being performed by at least one of the data network nodes in the resulting set of data network nodes;
enabling a transaction operation operable to cause the deletion of the network service by deleting each change of network service information in created, added andor updated data network nodes in the change-set of network service information (X) associated with the network service instance corresponding to the creation of the network service that is to be deleted, and
committing the transaction operation to the data network in order to instantiate and mutually configure the set of data network nodes in the data network.
15. A method according to claim 11, wherein the change management request is based on a data model describing the network service in the data network and is mapped to corresponding network service information in one or more data network nodes in the data network for implementing the network service.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A controlled release pharmaceutical composition for oral use comprising a strontium salt.
2. The pharmaceutical composition according to claim 1, wherein the water-solubility of the strontium salt is at the most about 200 gl at room temperature (20-25\xb0 C.).
3. The pharmaceutical A composition according to claim 1, wherein the water solubility of the strontium salt is at least 0.1 gl at room temperature (20-25\xb0 C.).
4. The pharmaceutical composition according to claim 1, wherein the water solubility of the strontium salt is at least 1 gl at room temperature of (20-25\xb0 C.).
5. The pharmaceutical composition according to claim 1 for administration once daily at bed-time.
6. The pharmaceutical composition according to claim 1 comprising at least 0.01 g of strontium, wherein the strontium is calculated as strontium ion.
7. The pharmaceutical composition according to claim 1, comprising at least about 0.5 g of strontium, wherein the strontium is calculated as ionic strontium ion.
8. The pharmaceutical composition according to claim 1, wherein the strontium salt is released from the composition in such a manner that the amplitude (difference between peak and nadir) of the plasma concentration relative to the peak level is less than about 40% after repeated administration of the composition to a subject once daily.
9. The pharmaceutical composition according to claim 1, wherein the composition when tested in an in vitro dissolution test releases strontium ion from the strontium salt containing composition in the following manner:
within the first 30 minutes of the test at the most about 10% ww of the strontium ion is released;
within the first 4 hours of the test at the most about 70% ww of the strontium ion is released; and
within the first 14 hours of the test about 70% ww or more of the strontium & ion is released.
10. The pharmaceutical composition according to claim 1, wherein the strontium salt is contained in a matrix that governs the release.
11. The pharmaceutical composition according to claim 1, wherein the composition is coated with a controlled release coating governing the release of the strontium salt.
12. The pharmaceutical composition according to claim 1, wherein the strontium salt comprises is strontium salts of an organic or an inorganic acid.
13. The pharmaceutical composition according to claim 12, wherein the inorganic acid comprises hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, nitrous acid, phosphoric acid, phosphinic acid, phosphonic acid, sulfonic acid, sulfuric acid, sulfurous acid, disulfuric acid or boric acid.
14. The pharmaceutical composition according to claim 12, wherein the organic acid comprises acetic acid, C2H5COOH, C3H7COOH, C4H9COOH, (COOH)2, CH2(COOH)2, C2H4(COOH)2, C3H6(COOH)2, C4H8(COOH)2, C5H10(COOH)2, fumaric acid, maleic acid, malonic acid lactic acid, citric acid, tartaric acid, oxalic acid, ascorbic acid, benzoic acid, salicylic acid, phthalic acid, carbonic acid, formic acid, acid, L- and D-glutamic acid, L- and D-aspartic acid, glucosamine sulphate, L-threonate, trifluoroacetic acid or ranelic acid.
15. The pharmaceutical composition according to claim 12, wherein the acid is a non-chelator of strontium.
16. The pharmaceutical composition according to claim 12, wherein the salt is in hydrate, anhydrous, solvate, polymorphous, amorphous, crystalline, microcrystalline or polymeric form.
17. The pharmaceutical composition according to claim 11, wherein the salt comprises strontium citrate, strontium succinate, strontium fumarate, strontium ascorbate, strontium tartrate, strontium glutarate, strontium malonate, strontium methanesulfonate, strontium benzenesulfonate, strontium glucosamine sulphate, strontium L-threonate, or mixtures thereof.
18. The pharmaceutical composition according to claim 12, wherein the anion of the strontium salts acid is derived from a monoprotic, a diprotic or a triprotic acid.
19. A method for treatment andor prophylaxis of a cartilage andor bone disease andor conditions resulting in a dysregulation of cartilage andor bone metabolism in a mammal, the method comprising administering a single daily dose of a controlled release pharmaceutical composition comprising a strontium salt, wherein the amount of strontium salt is adjusted so that the pharmaceutical composition is suitable for administration once daily.
20. A method for treatment andor prophylaxis of a cartilage andor bone disease andor conditions resulting in a dysregulation of cartilage andor bone metabolism in a male mammal, the method comprising administering a controlled release pharmaceutical composition comprising a strontium salt, wherein the amount of strontium salt is adjusted so that the pharmaceutical composition is suitable for administration once daily.
21-23. (canceled)
24. A method for preventing in a subject a cartilage andor bone disease andor conditions resulting in a dysregulation of cartilage andor bone metabolism in a mammal, the method comprising administering a controlled release pharmaceutical composition comprising a strontium salt, wherein the amount of strontium salt is adjusted so that the pharmaceutical composition is suitable for administration once daily.
25. The method according to claim 24, wherein the subject is a female having a bone mineral density, BMD, of more than 1 SD below the young adult female mean.
26. The method according to claim 24, wherein the subject is a female having a BMD below the adult female mean for women of the same age.
27. The method according to claim 24, wherein the subject is a male having a BMD of more than 1 SD below the young adult male mean.
28. The method according to claim 24, wherein the subject is a male having a BMD below the adult male mean for men of the same age.
29. The method according to claim 24, wherein the subject is a female having a level of a specific biomarker of bone resorption, of more than 1 SD above the young adult female mean.
30. The method according to claim 24, wherein the subject is a female having a level of a specific biomarker of bone resorption above the adult female mean for women of the same age.
31. The method according to claim 24, wherein the subject is a male having a level of a specific biomarker of bone resorption, of more than 1 SD above the young adult male mean.
32. The method according to claim 24, wherein the subject is a male having a level of a specific biomarker of bone resorption above the adult mean for men of the same age.
33. The method according to claim 24, wherein the subject is a 20 year or older female.
34. The method according to claim 24, wherein the subject is a female that is about the same age as her age of onset of menopause.
35. The method according to claim 24, wherein the subject is a female who is about 6 months or more beyond the onset of menopause.
36. The method according to claim 24, wherein the subject is a 20 year or older male.
37. The method according to claim 24, wherein the daily dose of strontium administered is at least 0.01 g of strontium.
38. The method according to claim 24, wherein the method further comprises administering an amount of calcium to a subject in need thereof.
39. The method according to claim 38 wherein the daily dose of calcium is at least about 0.01 g.
40. The method according to claim 39, wherein calcium is administered at least 0.5 h, after the administration of the strontium component.
41. The method according to claim 38, wherein calcium is administered at least 0.5 h, before the administration of the strontium component.
42. The method according to claim 24, wherein the method further comprises administering an amount of vitamin D to a subject in need thereof.
43. The method according to claim 42, wherein the vitamin is vitamin D3 and the daily dose is at least about 1 \u03bcg.
44. The method according to claim 43, wherein the daily dose of vitamin D3 is from about 5 \u03bcg to about 30 \u03bcg.
45. The method according to claim 42, wherein vitamin D is vitamin D2, and the daily dose of vitamin D2 is at least 1 \u03bcg.
46. The method according to claim 45, wherein the daily dose of vitamin D2 is from about 5 \u03bcg to about 125 \u03bcg.
47. The method according to claim 42, wherein the strontium and the vitamin D components are administered simultaneously.
48. A method for treating andor preventing secondary osteoporosis in a subject, the method comprising administering an effective amount of a strontium salt to the subject.
49. The method according to claim 48, wherein the secondary osteoporosis is induced by endocrine diseases, metabolic causes, nutritional conditions, drug substances andor disorders of the collagen metabolism.
50. A method for preventing drug induced secondary osteoporosis in a subject, the method comprising administering to the subject a prophylactic amount of a strontium salt before, during or after treatment of the subject with the drug substance that induces secondary osteoporosis.
51. The method according to claim 50, wherein the administration takes place substantially simultaneously with administration of the drug substance that induces osteoporosis.
52. The method according to claim 51, wherein the strontium salt and the drug substance that induces osteoporosis are contained in the same pharmaceutical composition.
53. A pharmaceutical composition comprising a strontium salt and a drug substance that induces osteoporosis together with a pharmaceutically acceptable excipient.
54. The method according to claim 19, wherein the cartilage andor bone disease andor conditions resulting in a dysregulation of cartilage andor bone metabolism in a mammal, comprises osteoporosis, osteoarthritis, osteopetrosis, osteopenia and Paget’s disease, hypercalcemia of malignancy, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, osteodystrophy, myositis ossificans, Bechterew’s disease, malignant hypercalcemia, osteolytic lesions produced by bone metastasis, bone pain due to bone metastasis, bone loss due to sex steroid hormone deficiency, bone abnormalities due to steroid hormone treatment, bone abnormalities caused by cancer therapeutics, osteomalacia, Bechet’s disease, hyperostosis, metastatic bone disease, immobilization induced osteopenia or osteoporosis, or glucocorticoid-induced osteopenia or osteoporosis, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, for the improvement of fracture healing after traumatic or atraumatic fracture, for the improvement of implant stability and for the maintenance or increase of energy level, for building up or strengthening muscle tissues or for weight gain.
55. The method according to claim 20, wherein the cartilage andor bone disease andor conditions resulting in a dysregulation of cartilage andor bone metabolism in a mammal, comprises osteoporosis, osteoarthritis, osteopetrosis, osteopenia and Paget’s disease, hypercalcemia of malignancy, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, osteodystrophy, myositis ossificans, Bechterew’s disease, malignant hypercalcemia, osteolytic lesions produced by bone metastasis, bone pain due to bone metastasis, bone loss due to sex steroid hormone deficiency, bone abnormalities due to steroid hormone treatment, bone abnormalities caused by cancer therapeutics, osteomalacia, Bechet’s disease, hyperostosis, metastatic bone disease, immobilization-induced osteopenia or osteoporosis, or glucocorticoid-induced osteopenia or osteoporosis, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, for the improvement of fracture healing after traumatic or atraumatic fracture, for the improvement of implant stability and for the maintenance or increase of energy level, for building up or strengthening muscle tissues or for weight gain.
56. The method according to claim 24, wherein the cartilage andor bone disease andor conditions resulting in a dysregulation of cartilage andor bone metabolism, comprises osteoporosis, osteoarthritis, osteopetrosis, osteopenia and Paget’s disease, hypercalcemia of malignancy, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, osteodystrophy, myositis ossificans, Bechterew’s disease, malignant hypercalcemia, osteolytic lesions produced by bone metastasis, bone pain due to bone metastasis, bone loss due to sex steroid hormone deficiency, bone abnormalities due to steroid hormone treatment, bone abnormalities caused by cancer therapeutics, osteomalacia, Bechet’s disease, hyperostosis, metastatic bone disease, immobilization-induced osteopenia or osteoporosis, or glucocorticoid-induced osteopenia or osteoporosis, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, for the improvement of fracture healing after traumatic or atraumatic fracture, and for the maintenance or increase of energy level, for building up or strengthening muscle tissues or for weight gain.
57. The pharmaceutical composition of claim 8, wherein the repeated administration comprises repeated administration of the composition to the subject once daily for at least seven days.
58. The method of claim 19, wherein the strontium salt comprises at least 0.5 g of strontium.
59. The method of claim 19, wherein the pharmaceutical composition is administered orally.
60. The method of claim 20, wherein the pharmaceutical composition is administered in an amount and frequency that gives a daily dose of from about 0.25 g to about 1.5 g strontium ion.
61. The method of claim 20, wherein the pharmaceutical composition is administered orally.
62. The method of claim 24, wherein the pharmaceutical composition is administered in an amount and frequency that gives a daily dose of from about 0.25 g to about 1.5 g strontium ion.
63. The method of claim 24, wherein the pharmaceutical composition is administered orally.