CN1187130A - Bisphosphonates prevent bone loss associated with immunosuppressive therapy - Google Patents
Bisphosphonates prevent bone loss associated with immunosuppressive therapy Download PDFInfo
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- CN1187130A CN1187130A CN96194562A CN96194562A CN1187130A CN 1187130 A CN1187130 A CN 1187130A CN 96194562 A CN96194562 A CN 96194562A CN 96194562 A CN96194562 A CN 96194562A CN 1187130 A CN1187130 A CN 1187130A
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- alendronate
- immunosuppressive therapy
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- diphosphonic acid
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Abstract
Bisphosphonate, particularly alendronate, can prevent or treat bone loss associated with immunosuppressive therapy, whether or not the immunosuppressive therapy is associated with an organ transplant.
Description
The general introduction of invention
The present invention relates to be the prevention bone loss relevant with immunosuppressive therapy, particularly when this therapy was used in combination with organ transplantation, diphosphate is the application of alendronate particularly.
Background of invention
The patient who suffers from the various diseases that needs organ or bone marrow transplantation is in order to suppress the various medicines of trend needs of this organ of body resistance.This situation generally requires the patient to take one or more immunosuppressant, as cyclosporin etc., often with the epinephrine corticosteroid, as common uses such as methylprednisolones.Unfortunately, the combination of potential symptom, inertia or movable minimizing and Drug therapy makes these patients produce higher bone loss.
And, attempting therapeutic agent with various immunosuppressant do treatment various diseases, these diseases not necessarily comprise organ transplantation and comprise as rheumatoid arthritis, psoriasis, enteritis and the nephrotic syndrome.These patients also are in the highly dangerous of bone loss.
People wish to make the patient who is carrying out organ transplantation or the acceptance immunosuppressive therapy relevant with organ transplantation or other potential medical symptoms to exempt or prevention bone loss disease.
The detailed description of invention
According to the present invention, it has been found that diphosphate can prevent the bone loss relevant with immunosuppressive therapy with treatment when with prevention or the administration of treatment effective dose.Particularly, effective salt on alendronate (4-amino-1-hydroxy butylidene-1,1-diphosphate) or its materia medica when with prevention or the administration of treatment effective dose, can prevent the bone loss relevant with immunosuppressive therapy with treatment.
Another aspect of the present invention is by diphosphate is lost with effective dose administration prevention or the treatment bone relevant with immunosuppressive therapy, no matter whether this therapy is followed organ transplantation, diphosphate wherein is selected from following group: alendronate, etidronate (1-hydroxyl-ethylidene-diphosphonic acid), silks rice hydrochlorate (3-amino-1-hydroxy propylidene-1, the 1-diphosphate), risedronate (2-(3-pyridine radicals)-1-hydroxy ethylene-diphosphonic acid), BONE-FOS (dichloro methylene-diphosphonic acid), tiludronate (chloro-4-phenyl thio-methylene-diphosphonic acid), acceptable salt on the materia medica of ibandronic acid (1-hydroxyl-3 (methyl amyl amino)-propylidene-diphosphonic acid) and above-mentioned any acid, and any mixture in any and these salt in these acid.Above-mentioned all chemical compounds are all known in the art.
According to the present invention, the patient who generally carries out immunosuppressive therapy will accept cyclosporin or similar medicine.In addition, this patient also can accept prednisone or other corticosteroid simultaneously.
In whole description and the claim, used following definition:
The quantum volueris of the order of severity of the bone loss that " prevention effective dose "--alendronate is used for preventing or minimizing is relevant with immunosuppressive therapy is wherein no matter whether this immunotherapy is accompanied by organ transplantation.
" treatment effective dose "--alendronate is used for treating the quantum volueris of the bone loss relevant with immunosuppressive therapy, wherein no matter whether this immunotherapy is accompanied by organ transplantation.
The preferred aspect of the present invention, the patient will accept alendronate.Alendronate can be according to United States Patent (USP) 5,019, and 651,4,992, any method preparation described in the U. S. application serial number of submitting on August 4th, 007 and 1,994 08/286,151, this paper is list of references with above-listed various patent citations.On the alendronate materia medica acceptable salt comprise alkali metal (as Na, K) alkaline-earth metal (as Ca) salt, inorganic acid salt example hydrochloric acid salt, and acylate such as citric acid and amino acid salts.Single sodium-salt form of particular certain cancers form, particularly three hydrations.
Many bisphosphonate compounds of the present invention can both be with the peroral dosage form administration, these peroral dosage forms such as tablet, capsule (respectively comprising sustained release forms or timing release dosage form), pill, powder, granule, elixir, paste, tincture, suspension, syrup and emulsion.Simultaneously they can also intravenous (gradation injection or infusion), intraperitoneal, subcutaneous or intramuscular mode administration, all these occupation modes are all known the those of ordinary skill of pharmaceutical field.The amount of effective and avirulent bisphosphonate compound can be used in the loss of prevention bone.
Use the dosage range of method required for protection to select according to various factors, these factors comprise: type, age, body weight, sex and patient's medical symptom; The order of severity of symptom; Route of administration; Patient's kidney and liver function; And used particular compound or its salt.Doctor that ordinary skill is skilled or clinical staff can determine at an easy rate and leave and prevent and/or treat the medicine that bone loses required effective dose.
When alendronate is diphosphate, oral dose of the present invention will change between about 1.0mg/kg/day at every kg body weight 0.05mg every day (mg/kg/day).The scope of the preferred oral dosage of human about 2.5-50mg/kg/day of accumulated dose every day during effective treatment, preferable amount are 5,10 or 20mg/ days.
Alendronate can single daily dose or fractionated dose administration.Hope is under the situation that does not have feed, and preferred ante cibum is as administration in about before the meal 30 minutes to 2 hours early, so that it can fully absorb.
In the method for the invention, active component generally is to mix administration with suitable pharmaceutical diluents, excipient or carrier (general designation " carrier mass " here), selecting then that these materials are suitable decided on form of medication, be oral tablet, capsule, elixir, syrup etc., also will put into practice compatible with conventional medicine.For example, concerning oral with tablet or capsule form, this active component can with acceptable inert carrier on a kind of oral, avirulent materia medica, as combinations such as lactose, starch, sucrose, glucose, methylcellulose, magnesium stearate, mannitol, sorbitol, cross-linked carboxymethyl cellulose sodium; Concerning oral with liquid form, this oral drugs component can combine with acceptable inert carrier on any oral, avirulence materia medica such as ethanol, glycerol, water etc.And, when needs or in case of necessity, also can be incorporated into suitable adhesive, lubricant, disintegrating agent and coloring agent in the mixture of active component and inert carrier material.Suitable adhesive comprises starch, gelatin, natural sugar, as glucose, Lactis Anhydrous, free-pouring lactose, β lactose and corn sweetener, natural and rubber polymer such as arabic gum, Tragacanth or sodium alginate, carboxymethyl cellulose, Polyethylene Glycol, wax etc.Used lubricant comprises enuatrol, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride etc. in these dosage forms.At United States Patent (USP) 5,358, particularly preferred alendronate tablet has been described in 941, this paper is this patent citation list of references.
In the inventive method used chemical compound also can with the soluble polymer coupling, as the target pharmaceutical carrier.This base polymer comprises polyvinylpyrrolidone, pyran co-polymer, poly-hydroxypropyl-Methacrylamide etc.
Standing the patient of immunosuppressive therapy, can be the sex at any age.The women can be before the menopause or after the menopause.
The embodiment of following indefiniteness be used for illustrating better of the present invention.Prevention and treatment that the bone that embodiment 1alendronate brings out cyclosporin loses
In clinical research, selected 220 men and women to estimate the effect of alendronate to prevention and the treatment bone loss relevant with immunosuppressive therapy.All patients are accepting organ transplantation; Majority is to accept heart, lung or liver transplantation.The patient is divided into 5 groups at random, after transplanting, begin to allow in the week they or take placebo, perhaps take 2.5,5,10 or 20mg/ days alendronate took 1 year.Except the cyclosporin and the steroidal class of standard consumption, outside prednisone, all patients also take every day 1000mg calcium and every day 250IU vitamin D.
The bone density of monitoring spinal column and hip also writes down all fracture incidence rates.
After 1 year, the patient who takes alendronate (with any dosage) has the statistical significance significance to increase than the BMD value of its spinal column of the patient who takes placebo and hip, and fracture also reduces.Can be observed this result from the lower two layers meaning: can see beginning to have the patient B MD of low BMD value to increase.Also observe the not low patient of beginning BMD and kept BMD.So alendronate can prevent the bone loss relevant with immunosuppressive therapy with treatment.
Claims (14)
1. the method for the prevention bone loss relevant with immunosuppressive therapy with treatment, this method comprises: take a kind of diphosphate of effective dose for the patient who lives through immunosuppressive therapy, this diphosphate is selected from following group: alendronate, etidronate (1-hydroxyl-ethylidene-diphosphonic acid), silks rice hydrochlorate (3-amino-1-hydroxy propylidene-1, the 1-diphosphate), risedronate (2-(3-pyridine radicals)-1-hydroxy ethylene-diphosphonic acid), BONE-FOS (dichloro methylene-diphosphonic acid), tiludronate (chloro-4-phenyl thio-methylene-diphosphonic acid), ibandronic acid (1-hydroxyl-3 (methyl amyl amino)-propylidene-diphosphonic acid), acceptable salt and composition thereof on the materia medica of above-mentioned any acid.
2. according to the process of claim 1 wherein that the patient is accepting the immunosuppressive therapy relevant with organ transplantation.
3. according to the method for claim 2, it comprises uses alendronate or the acceptable salt of its medicine.
4. according to the method for claim 3, wherein alendronate is the single sodium-salt forms of three hydrations.
5. according to the method for claim 4, wherein alendronate is with the administration of prevention effective dose.
6. according to the method for claim 5, wherein alendronate is oral.
7. according to the method for claim 5, wherein alendronate can arrive the dosed administration of 50mg every day 2.5.
8. according to the method for claim 7, wherein alendronate can every day 5mg, the dosed administration of 10mg or 20mg.
9. the method for the treatment bone loss relevant with immunosuppressive therapy, it comprises to the patient who lives through immunosuppressive therapy takes acceptable salt on the alendronate of treatment effective dose or its materia medica.
10. according to the method for claim 9, wherein alendronate is the single sodium-salt forms of three hydrations.
11. according to the method for claim 10, wherein alendronate can be oral.
12. according to the method for claim 10, wherein alendronate can arrive the dosed administration of 50mg every day 2.5.
13. according to the method for claim 12, wherein alendronate can every day 5mg, the dosed administration of 10mg or 20mg.
14. according to the method for claim 9, wherein this immunosuppressive therapy is relevant with organ transplantation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96194562A CN1187130A (en) | 1995-06-06 | 1996-06-03 | Bisphosphonates prevent bone loss associated with immunosuppressive therapy |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/471,466 | 1995-06-06 | ||
| CN96194562A CN1187130A (en) | 1995-06-06 | 1996-06-03 | Bisphosphonates prevent bone loss associated with immunosuppressive therapy |
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| Publication Number | Publication Date |
|---|---|
| CN1187130A true CN1187130A (en) | 1998-07-08 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96194562A Pending CN1187130A (en) | 1995-06-06 | 1996-06-03 | Bisphosphonates prevent bone loss associated with immunosuppressive therapy |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100372539C (en) * | 2001-10-19 | 2008-03-05 | 诺瓦提斯公司 | Pharmaceutical composition for use for the treatment of malignancies comprising in combination a bisphosphonates, a cox-2 inhibitor and a taxol |
| CN110250356A (en) * | 2019-06-11 | 2019-09-20 | 云南农业大学 | Application of the diphosphate in broiler fodder |
-
1996
- 1996-06-03 CN CN96194562A patent/CN1187130A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100372539C (en) * | 2001-10-19 | 2008-03-05 | 诺瓦提斯公司 | Pharmaceutical composition for use for the treatment of malignancies comprising in combination a bisphosphonates, a cox-2 inhibitor and a taxol |
| CN110250356A (en) * | 2019-06-11 | 2019-09-20 | 云南农业大学 | Application of the diphosphate in broiler fodder |
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