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Combination treatment with strontium for the prophylaxis and/or treatment of cartilage and/or bone conditions

a technology of cartilage and strontium, applied in the field of combination treatment, can solve the problems of increased risk of cancer and cardiovascular disease, loss of bone at a rate faster than the accretion of bone, and net loss of bone, and achieve the effect of prophylaxis and/or treatment of cartilag

Inactive Publication Date: 2006-12-07
OSTEOLOGIX AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007] In one aspect, the invention relates to a method for the treatment and / or prophylaxis of a cartilage and / or bone disease and / or conditions resulting in a dysregulation of cartilage and / or bone metabolism in a mammal, such as, e.g., a human female or male adult, adolescent or a child, such as, e.g., 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 and for weight gain, the method comprising administering to a subject in need thereof a) a strontium-containing compound and b) one or more further active substances capable of reducing the incidence of bone fracture and / or increasing bone density and / or improving healing of fractured bone.
[0008] In one embodiment of the method, the strontium-containing compound and one or more further active substances capable of reducing the incidence of bone fracture and / or increasing bone density and / or improving healing of fractured bone are administered in amounts that render the combination of the two effective in treating a cartilage and / or bone disease.

Problems solved by technology

The mechanism of bone loss in osteoporosis is believed to involve an imbalance in the process of bone remodeling.
However, in people with osteoporosis an imbalance in this remodeling process develops, resulting in loss of bone at a rate faster than the accretion of bone.
The decline in endogenous oestrogen production leads to an elevated metabolic activity in the bone tissue where the increase in osteoclast mediated bone resorption surpasses the more modest increase in bone formation, resulting in a net loss of bone.
SERM's and especially HRT is associated with significant side effects, such as increased risk of cancer and cardiovascular disease, whereas bisphosphonates in addition to a potent antiresorptive effect also decreases bone formation to a similar extent, implying that they loose their therapeutic effect after few years of treatment.

Method used

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  • Combination treatment with strontium for the prophylaxis and/or treatment of cartilage and/or bone conditions

Examples

Experimental program
Comparison scheme
Effect test

example 1

General Method for Preparation of Crystalline Salts of Strontium by Precipitation from Dissolved Strontium Chloride and Dissolved Sodium Salts of the Appropriate Carboxylic Anions

[0178] In a glass-beaker of 100 mL volume, 5 g of the sodium salt of the carboxylic acid was dissolved in a small volume of water that was slightly heated at temperatures not greater than 30-50° C. The final volume was 25-50 mL. In another beaker 10 g of SrCl2 (SrCl2 hexahydrate, Sigma-Aldrich 43,966-5) was dissolved in 100 mL of water. This latter solution was slowly decanted into the first solution of the dissolved sodium salt. The transfer continued until an initial cloudiness was observed, which resulted in a total volume of 50-100 mL. The solution was allowed to rest at room temperature (22-24° C.) for several days until significant amounts of crystallized precipitate of the organic strontium salt appeared.

[0179] The reaction that proceeds is exemplified by the reaction between strontium ions and so...

example 2

General Method for Preparation of Crystalline Salts by Neutralisation of Carboxylic Acids with Strontium Hydroxide

[0183] A small amount of the organic acid proper (0.75-3 g, see table below) was dissolved in water by heating to temperatures between 30° C.-50° C. Then, strontium hydroxide (Sigma Aldrich, Sr (OH)2*8H2O, MW 265.71, CAS no. 311-10-0, approx. 10 g / L) was slowly added. Then, a magnetic stirring rod was added and the stirring and gentle heating (i.e. 30-50° C.) of the suspension was started. After some time, the solution clarifies and all the solid material dissolves. The heating is maintained, and after three hours of incubation, the solution is filtered while hot on a Büchner funnel. Very small amounts of impurities were left in the filter.

[0184] The filtrate was subsequently allowed to cool at room temperature overnight, which resulted in growth of fine-powdered crystals of the desired strontium salt. Further purifications of the salts can be performed by repeated re...

example 3

Determinations of Solubility of Organic Strontium Salts

Synthesis of Strontium Salts

[0185] The great majority of strontium salts could be obtained by reacting the sodium salt of the organic acid with strontium chloride following the general synthesis method described in example A. However, strontium citrate, strontium tartrate, strontium succinate and strontium α-ketoglutarate for the solubility investigations was obtained by synthesis from the free acid forms of the carboxylic acid and strontium hydroxide as described in example 2. Strontium glutamate was obtained as described in example 4, using an incubation temperature of 100° C. and using strontium chloride and L-glutamic acid for the synthesis for obtaining pure and homogeneous hexahydrate crystals of strontium glutamate. As described in example 4 the strontium glutamate salt obtained by this method is distinct from a previously described form of crystalline strontium L-glutamate. Detailed investigations of solubility were ...

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Abstract

A combination treatment, wherein a strontium-containing compound together with one or more active substances capable of reducing the incidence of bone fracture and / or increasing bone density and / or improving healing of fractured bone and / or improving bone quality are administered for use in the treatment and / or prophylaxis of cartilage and / or bone conditions.

Description

FIELD OF THE INVENTION [0001] The present application relates to a combination treatment, wherein a strontium-containing compound together with one or more active substances capable of reducing the incidence of bone fracture and / or increasing bone density and / or improving healing of fractured bone and / or improving bone quality are administered for use in the treatment and / or prophylaxis of cartilage and / or bone conditions. BACKGROUND OF THE INVENTION [0002] Osteoporosis is the most common form of metabolic bone disease in humans. It is a condition, which affects a very large number of people all over the world, and as the number of elderly people is set to rise dramatically in the coming decades in most countries, the prevalence and impact of osteoporosis will also increase. The disease is characterized pathologically by an absolute decrease in the amount of bone mass and the structural quality of bone, and clinically by increased susceptibility to fractures. In fact, osteoporosis i...

Claims

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Application Information

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IPC IPC(8): A61K33/24A61K33/06A61K31/592A61K31/593A61K45/06A61P19/08
CPCA61K31/592A61K31/593A61K33/06A61K33/24A61K45/06A61K2300/00A61P1/02A61P19/00A61P19/02A61P19/08A61P19/10A61P29/00A61P43/00
Inventor HANSEN, CHRISTIANNILSSON, HENRIKCHRISTGAU, STEPHAN
Owner OSTEOLOGIX AS
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