DE2360798A1 - Calcium deposition influencing pharmaceutical/cosmetic prepns. - contg. polymethylenephosphonic acid cpds. - Google Patents
Calcium deposition influencing pharmaceutical/cosmetic prepns. - contg. polymethylenephosphonic acid cpds.Info
- Publication number
- DE2360798A1 DE2360798A1 DE2360798A DE2360798A DE2360798A1 DE 2360798 A1 DE2360798 A1 DE 2360798A1 DE 2360798 A DE2360798 A DE 2360798A DE 2360798 A DE2360798 A DE 2360798A DE 2360798 A1 DE2360798 A1 DE 2360798A1
- Authority
- DE
- Germany
- Prior art keywords
- disorders
- ch2cl
- pharmaceutical
- salts
- disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000002537 cosmetic Substances 0.000 title claims abstract description 8
- 230000008021 deposition Effects 0.000 title claims description 7
- 239000011575 calcium Substances 0.000 title description 8
- 239000002253 acid Substances 0.000 title description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title description 5
- 229910052791 calcium Inorganic materials 0.000 title description 5
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 238000004090 dissolution Methods 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 15
- 150000003009 phosphonic acids Chemical class 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 14
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 abstract description 8
- 208000035475 disorder Diseases 0.000 abstract description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 abstract description 2
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 2
- 206010006811 Bursitis Diseases 0.000 abstract description 2
- 208000002064 Dental Plaque Diseases 0.000 abstract description 2
- 208000037147 Hypercalcaemia Diseases 0.000 abstract description 2
- 206010049933 Hypophosphatasia Diseases 0.000 abstract description 2
- 208000000913 Kidney Calculi Diseases 0.000 abstract description 2
- 208000010358 Myositis Ossificans Diseases 0.000 abstract description 2
- 206010029148 Nephrolithiasis Diseases 0.000 abstract description 2
- 206010029240 Neuritis Diseases 0.000 abstract description 2
- 208000010191 Osteitis Deformans Diseases 0.000 abstract description 2
- 208000001132 Osteoporosis Diseases 0.000 abstract description 2
- 208000027868 Paget disease Diseases 0.000 abstract description 2
- 208000006568 Urinary Bladder Calculi Diseases 0.000 abstract description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 2
- 206010003246 arthritis Diseases 0.000 abstract description 2
- 201000001883 cholelithiasis Diseases 0.000 abstract description 2
- 208000001130 gallstones Diseases 0.000 abstract description 2
- 230000000148 hypercalcaemia Effects 0.000 abstract description 2
- 208000027202 mammary Paget disease Diseases 0.000 abstract description 2
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 abstract 2
- 239000013543 active substance Substances 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 230000000849 parathyroid Effects 0.000 abstract 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 16
- 201000010099 disease Diseases 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000004434 Calcinosis Diseases 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 208000006558 Dental Calculus Diseases 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 230000002308 calcification Effects 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 239000004141 Sodium laurylsulphate Substances 0.000 description 3
- 229930003316 Vitamin D Natural products 0.000 description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 229910052586 apatite Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000002324 mouth wash Substances 0.000 description 3
- 229940051866 mouthwash Drugs 0.000 description 3
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 3
- 239000004575 stone Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000000606 toothpaste Substances 0.000 description 3
- 235000019166 vitamin D Nutrition 0.000 description 3
- 239000011710 vitamin D Substances 0.000 description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 description 3
- 229940046008 vitamin d Drugs 0.000 description 3
- 239000000341 volatile oil Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- -1 mono- Chemical class 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 229940034610 toothpaste Drugs 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010070918 Bone deformity Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 201000002980 Hyperparathyroidism Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- WXQWKYFPCLREEY-UHFFFAOYSA-N azane;ethanol Chemical class N.CCO.CCO.CCO WXQWKYFPCLREEY-UHFFFAOYSA-N 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005048 flame photometry Methods 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229940041476 lactose 100 mg Drugs 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical group 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- C07F9/3821—Acyclic saturated acids which can have further substituents on alkyl substituted by B, Si, P or a metal
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Birds (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
4000 Düsseldorf, den 28. 11. 1975 Henkel&Cie GmbH 4000 Düsseldorf, November 28, 1975 Henkel & Cie GmbH
Henkel Straße 67 PatentabteilungHenkel Strasse 67 patent department
Dr. Ar/GeDr. Ar / Ge
Patentanmeldung D 4810 Patent application D 4810
"Pharmazeutische oder kosmetische Präparate""Pharmaceutical or Cosmetic Preparations"
Gegenstand der Erfindung sind pharmazeutische oder kosmetische Präparate zur Beeinflussung der Ablagerung und Auflösung von schwerlöslichen Calciumsalzen unter Verwendung von bestimmten Phosphonsäuren oder deren wasserlösliche Salze als Wirkstoff.The invention relates to pharmaceutical or cosmetic products Preparations for influencing the deposition and dissolution of poorly soluble calcium salts with the use of certain Phosphonic acids or their water-soluble salts as active ingredients.
In der Human- und Veterinärmedizin sind eine Anzahl von Erkrankungen bekannt, die vorwiegend odev teilweise mit der anomalen Ablagerung oder Auflösung von schwerlöslichen Calciumsalzen im Körper verbunden sind. Man kann diese Erkrankungen in zwei Kategorien einteilen:In human and veterinary medicine there are a number of diseases known, which mainly odev partly with the anomalous deposition or dissolution of poorly soluble calcium salts connected in the body. These diseases can be divided into two categories:
1. Durch unerwünschte Ablagerung von schwerlöslichen Calciumsalzen, insbesondere Calciumphosphät, treten Knochenmißbildungen, pathologische Verhärtung von Geweben und Abscheidungen in Organen auf.1. By undesired deposition of poorly soluble calcium salts, especially calcium phosphate, bone deformities occur, pathological hardening of tissues and deposits in organs.
2. Durch anomale Auflösung von harter Knochensubstanz, die nur unvollständig durch "Knochenkalk" ersetzt wird, treten krankhafte Veränderungen auf. Diese Auflösung ist häufig von pathologisch hohen Calcium- und Phosphat-Konzentrationen im Plasma begleitet.2. By abnormal dissolution of hard bone substance that only is incompletely replaced by "bone lime", pathological changes occur. This resolution is often pathological accompanied by high calcium and phosphate concentrations in the plasma.
Zur ersten Kategorie zählen Erkrankungen wie Arthritis, Neuritis, Bursitis, Tenditis und andere Entzündungserkrankungen, bei denen anomale Abscheidung von Oalciumphosphat in den betroffenen Körperteilen begünstigt ist. Bei durch hormonelle Störungen bedingtem Hyperparathyroidismus kann in Verbindung mit Hyperkalzämie Kalkablagerung in vielen Organen erfolgen.The first category includes diseases such as arthritis, neuritis, bursitis, tenditis and other inflammatory diseases, in which abnormal deposition of calcium phosphate in the affected body parts is favored. In the case of hyperparathyroidism caused by hormonal disorders, in connection with hypercalcemia calcium deposition occurs in many organs.
— 2 -- 2 -
509826/093 8509826/093 8
Sd187 3. 0473 HD 001662)Sd187 3. 0473 HD 001662)
Myositis ossificans führt zu fortschreitender Verknöcherung der Muskulatur; bei der Bechterew*sehen Krankheit führt fortschreitende Verkalkung zu einer Verknöcherung der gesamten Wirbelsäule.Myositis ossificans leads to progressive ossification the muscles; in the ankylosing spondylitis disease leads progressive calcification leading to ossification of the entire spine.
Besonders verbreitet ist ferner die Arteriosklerose, bei der im fortgeschrittenen Stadium in der Regel Verkalkung der Arterien, insbesondere der Aorta auftritt. Auch unerwünschte Steinbildung wie Nierensteine, Gallensteine, Blasensteine und Speichelstein (Zahnstein) zählen hierzu, auch wenn diese · Steine oft nur als Nucleus eine Calciumphosphat-Abscheidung besitzen und sonst aus anderen Stoffen aufgebaut sind.Arteriosclerosis is also particularly widespread, in which, in the advanced stage, usually calcification of the Arteries, especially the aorta occurs. Also unwanted stone formation such as kidney stones, gallstones, bladder stones and salivary stone (tartar) are included, even if these stones are often only a calcium phosphate deposit as nucleus and are otherwise composed of other materials.
Zu der zweiten Kategorie von Erkrankungen zählen die Hypophosphatasia sowie die Osteoporose, bei der aus verschiedenen Ursachen eine unzureichende Neubildung von Knochensubstanz erfolgt. Ferner gehören in diese Kategorie die Paget'sche Krankheit, bei der die Auflösung von normaler Knochensubstanz gleichzeitig' mit der Neubildung von weichem, nur wenig kristallisiertem Gewebe erfolgt, sowie die Osteodystrophia fibrosa generalisata, eine Systemerkrankung mit regellosem Knochenabbau.The second category of diseases includes hypophosphatasia as well as osteoporosis, in which, for various reasons, insufficient regeneration of bone substance he follows. This category also includes Paget's disease, in which normal bone substance breaks down at the same time as the new formation of soft, only slightly crystallized Tissue occurs, as well as the osteodystrophia fibrosa generalisata, a systemic disease with irregular bone loss.
Eine völlig befriedigende Therapie all dieser Erkrankungen ist bisher nicht beschrieben worden, obwohl kontrollierte Diäten, Behandlung mit Fluoriden, mit Gesehleehtshormonen sowie vor allem mit dem Hormon Calcitonin vorgeschlagen und auch angewandt worden sind. In letzter Zeit ist auch die Behandlung mit bestimmten Phosphonaten, insbesondere 1.1-Diphosphonaten vorgeschlagen worden. . ;A completely satisfactory therapy for all of these diseases has not yet been described, although it is controlled Diets, treatment with fluorides, with eye hormones and especially with the hormone calcitonin are suggested and have also been applied. Recently, treatment with certain phosphonates, especially 1.1-diphosphonates, has also been used has been proposed. . ;
Es wurde nun gefunden, daß pharmazeutische oder kosmetische Präparate, welche Verbindungen der nachstehend angegebenen Struktur enthalten, -geeignet sind, Störungen des Calcium- bzw. Phosphatstoffwechsels sowie die damit verbundenen Erkrankungen therapeutisch und/oder prophylaktisch zu behandeln. Die Produkte sind dadurch gekennzeichnet, daß sie als Wirkstoff Verbindungen der folgenden FormelIt has now been found that pharmaceutical or cosmetic preparations containing compounds of the following Contain structure, are suitable, disorders of calcium or phosphate metabolism and the diseases associated with them treat therapeutically and / or prophylactically. The products are characterized in that they contain compounds as active ingredients the following formula
50 9826/09 3850 9826/09 38
ο οο ο
HO - P - CH2 - P - CH2R (I)HO - P - CH 2 - P - CH 2 R (I)
OH OHOH OH
oder deren wasserlösliche Salze enthalten, wobeior contain their water-soluble salts, wherein
ti
P -
OH0
ti
P -
OH
It
-Ρ0
It
-Ρ
11
ρ _0
11
ρ _
und n=l-7 m=l- 100 und X = -OH, -CH2OH oder -CHgCl bedeuten.and n = 1-7 m = 1-100 and X = -OH, -CH 2 OH or -CHgCl.
Im einzelnen kommen Verbindungen der nachstehenden Formeln II bis VI in Betracht:In detail, compounds of the following formulas II to VI come into consideration:
0 0 00 0 0
HO - P - CH0 - P - CH0 -P-OH (il)HO - P - CH 0 - P - CH 0 -P-OH (il)
1 £ \ c. ι1 £ \ c. ι
OH OH · OHOH OH OH
0 .0 00 .0 0
HO - P - CH2 - P - (CH 2)n - P - CH2 -P-OH (Hl) OH OH OH OHHO - P - CH 2 - P - (C H 2 ) n - P - CH 2 -P-OH (Hl) OH OH OH OH
η = 1 -η = 1 -
509826/093509826/093
ο οο ο
HO - P - (- CH2 - P -)m CH2Cl (IV)HO - P - (- CH 2 - P -) m CH 2 Cl (IV)
.Oh Oh.Oh oh
ο οο ο
HO-P-C-CH2-P -)m
OH OHHO-PC-CH 2 -P -) m
OH OH
0 00 0
P-C-CH2-P -)m OHPC-CH 2 -P -) m OH
OH OH (VI)OH OH (VI)
In den Formeln IV - VI bedeutet m = 1 - 100, vorzugsweise 1-8 und 50 - 100.In the formulas IV-VI, m = 1-100, preferably 1-8 and 50-100.
Verbindungen der Formel II werden hergestellt durch UmsatzCompounds of the formula II are produced by conversion
0
tt0
dd
ClCH2 - P - CH2Cl
ORClCH 2 - P - CH 2 Cl
OR
mit P(OR) oder NaP(O)(OR)2 (Michaelis-Arbusov-Reaktion) sowie anschließende saure Verseifung. Dabei bedeutet R einen niederen Alkylrest.with P (OR) or NaP (O) (OR) 2 (Michaelis-Arbusov reaction) and subsequent acidic saponification. R denotes a lower alkyl radical.
Verbindungen der Formel III werden erhalten durch Umsetzung von Phosphorverbindungen vom TypCompounds of the formula III are obtained by reacting phosphorus compounds of the type
(RO)2 P - (CH2)X - P(OR)2
mit (RO)2 (O)PCH2Cl
sowie anschließende saure Verseifung.
X hat den Wert 1 bis 8 und R bedeutet einen niederen Alkylresfc«(RO) 2 P - (CH 2 ) X - P (OR) 2 with (RO) 2 (O) PCH 2 Cl
as well as subsequent acid saponification.
X has the value 1 to 8 and R means a lower alkyl resistance
- 5 509826/0938 - 5 509826/0938
Durch Polymerisation von Verbindungen der Formel ClH2C P(OR)2 By polymerizing compounds of the formula ClH 2 CP (OR) 2
in Lösungsmitteln wie Tetrachloräthan bei Temperaturen von 150 bis 2200C und anschließende saure Hydrolyse in Gegenwart von Luft erhält man Verbindungen der Formel IV. Durch die Erhitzungsdauer kann der Polymerisationsgrad beeinflußt werden. Bei langem Erhitzen entstehen entweder hochpolymere Körper oder aber cyclische Verbindungen.compounds of the formula IV are obtained in solvents such as tetrachloroethane at temperatures from 150 to 220 ° C. and subsequent acid hydrolysis in the presence of air. The degree of polymerization can be influenced by the heating time. When heated for a long time, either highly polymeric bodies or cyclic compounds are formed.
Verbindungen der Formel V lassen sich herstellen, wenn durch Hydrolyse die CHpCl-Gruppe in Verbindungen der Formel IV in die CHjOH-Gruppe umgewandelt wird. Schließlich lassen sich Verbindungen der Formel VI herstel?.en durch Umsatz von Verbindungen der StrukturCompounds of the formula V can be prepared if by Hydrolysis the CHpCl group in compounds of the formula IV is converted into the CHjOH group. Finally, compounds of the formula VI can be prepared by reacting compounds of the structure
0.000.00
ClH0C - P - (- CH0P -) - CH0 - P - OR 2 t 2j 2 · t ClH 0 C - P - (- CH 0 P -) - CH 0 - P - OR 2 t 2j 2 * t
OR OR OROR OR OR
mit P(OR) oder NaP(O)(OR)0, wobei R wiederum einen niederen Alkylrest bedeutet.with P (OR) or NaP (O) (OR) 0 , where R in turn denotes a lower alkyl radical.
C.C.
Die oben beschriebenen Säuren können in bekannter Weise: durch ganze oder teilweise Neutralisation in die gewünschten Salze überführt werden.The acids described above can be converted into the desired salts in a known manner: by complete or partial neutralization.
Zur pharmazeutischen Anwendung kommen anstelle der freien Säure auch ihre pharmakologisch unbedenklichen Salze wie Natrium-, Kalium-, Magnesium-, Ammonium- und substituierten Ammoniumsalze wie Mono-, Di- oder .Tri-äthanolammoniumsalze in Frage,· Sowohl die partiellen Salze, in denen nur ein TeilFor pharmaceutical use come instead of the free Acids also like their pharmacologically acceptable salts Sodium, potassium, magnesium, ammonium and substituted ammonium salts such as mono-, di- or tri-ethanol ammonium salts in question · Both the partial salts in which only a part
- 6 -509826/0^38 - 6 - 509826/0 ^ 38
der aciden Protonen durch andere Kationen ersetzt ist, als auch Vollsalze können benutzt werden, jedoch sind partielle Salze, die in wäßriger Lösung annähernd neutral reagieren (pH 5 - 9), bevorzugt. Mischungen der vorgenannten Salze können ebenfalls angewandt werden.the acidic protons are replaced by other cations, as well as full salts can be used, but partial Salts which react almost neutrally in aqueous solution (pH 5-9) are preferred. Mixtures of the aforementioned salts can also be used.
Die Dosierung der verwendeten Verbindungen ist variabel und ist abhängig von der Art und Schwere der Erkrankung, Dauer der Behandlung und der jeweiligen Verbindung. Sie liegt im allgemeinen zwischen 0,05 - 500 mg pro kg Körpergewicht. Die bevorzugte Dosierung beträgt 1 - 50 mg pro kg Körpergewicht. Sie kann mehrmals täglich verabreicht werden, bevorzugt in oraler Applikation. Der bevorzugte Dosisbereich für die 01 ale Applikation beträgt 1 - IO mg pro kg Körpergewicht bei maximal 4- mal täglicher Verabreichung. Bei der Behandlung von Tieren können die Verbindungen auch gegebenenfalls dem Futter beigemengt werden. Die Wirkung der beanspruchten Verbindungen und deren Salze beruht vermutlich auf einer Wechselwirkung der Verbindungen mit der Kristalloberfläche des Calciumphosphats.The dosage of the compounds used is variable and depends on the type and severity of the disease, Duration of treatment and the respective connection. It is generally between 0.05 and 500 mg per kg of body weight. The preferred dosage is 1-50 mg per kg of body weight. It can be administered several times a day, preferably in oral application. The preferred dose range for oil administration is 1 to 10 mg per kg of body weight with a maximum of 4 times daily administration. In the Treatment of animals, the compounds can optionally also be added to the feed. The effect of the claimed compounds and their salts is probably based on an interaction of the compounds with the Crystal surface of the calcium phosphate.
Die Substanzen können zur Verabreichung in Tabletten, Pillen, Kapseln oder Injektionslösungen formuliert werden. Für Tiere können die Substanzen auch in Futter bzw. als Futterzusätze Verwendung finden. Gewünschtenfalls kommen auch Gemische von den genannten Phosphonsäuren oder von den wasserlöslichen Salzen in Betracht.The substances can be formulated for administration in tablets, pills, capsules or injection solutions. For animals the substances can also be used in feed or as feed additives. If desired, mixtures of the phosphonic acids mentioned or the water-soluble salts.
Bei Anwendung in kosmetischen Präparaten wie Mund- und Zahnpflegemitteln verhindern die erfindungsgemäß zur Anwendung gelangenden Phosphonsäuren bzw. ihre pharmakologisch unbedenklichen Salze die Bildung von Zahnstein. Die Konzentrationen an den genannten Stoffen liegen zwischen 0,01 und 5 Gew.-^.When used in cosmetic preparations such as oral and dental care products prevent the phosphonic acids used according to the invention or their pharmacologically harmless ones Salt the formation of tartar. The concentrations of the substances mentioned are between 0.01 and 5 wt .- ^.
509826/0938509826/0938
Die Wirksamkeit der erfindungsgemäßen Verbindungen zur Verhinderung von anomalen Kalkablagerungen läßt sich in vitro demonstrieren durch die Verzögerung der Kristallisation von Apatit.The effectiveness of the compounds according to the invention in preventing abnormal calcium deposits can be demonstrated in vitro by delaying crystallization of apatite.
Übersättigte Lösungen von Ca und HPOj, "-Ionen sind relativ stabil. Sie kristallisieren jedoch bei Zugabe von Apatit-Keimen nach der Reaktionsgleichung 5 Ca + + j5HP0j, + HpP-*Ca5(PO^),0H + 4 H+ unter Freisetzung von Protonen. Die Reaktion läßt sich durch Basentitration bei konstantem pH leicht verfolgen.Supersaturated solutions of Ca and HPOj, "ions are relatively stable. However, when apatite nuclei are added, they crystallize with release according to the reaction equation 5 Ca + + j5HP0j, + HpP- * Ca 5 (PO ^), 0H + 4 H + of protons The reaction can easily be followed by base titration at constant pH.
400 ml einer 0,0008 molaren KHPO1.-Losung werden mit 45 ml einer 0,012 molaren CaClp-Lösung versetzt und die klare . Lösung mit KOH auf pH 7Λ eingestellt, nachdem sie auf 35°C temperiert wurde. Nach JO Min., während derer sich der pH nicht änderte, wird eine Suspension von 100 mg Hydroxylapatit in 50 ml HpO zugesetzt. Die sofort einsetzende Kristallisation wird durch pH-Stat-Titration mit 0,05 η KOH verfolgt.400 ml of a 0.0008 molar KHPO 1 solution are mixed with 45 ml of a 0.012 molar CaClp solution and the clear. Solution adjusted to pH 7Λ with KOH after it has been tempered to 35 ° C. After 90 minutes, during which the pH did not change, a suspension of 100 mg of hydroxyapatite in 50 ml of HpO is added. The crystallization which started immediately is followed by pH stat titration with 0.05 η KOH.
Behandelt man den Apatit vor der Zugabe zur übersättigten Lösung für 6 Std. mit geringen Mengen der erfindungsgemäßen Phosphonsäuren in Form annähernd neutraler Salze, so findet eine starke Verzögerung der Kristallisation statt. Die Verringerung der Kristallisation liegt nach 4 Std. bei Werten zwischen 80 und 95 $· Auch nach längerer Zeit liegen die Werte noch erheblich unter denen des Versuchs ohne Zugabe von Inhibitoren. If the apatite is treated with small amounts of the invention for 6 hours before it is added to the supersaturated solution Phosphonic acids in the form of approximately neutral salts, there is a strong delay in crystallization. The reduction the crystallization is after 4 hours at values between 80 and 95 $. Even after a longer period of time, the values are still considerably below those of the experiment without the addition of inhibitors.
50 9826/0 93 850 9826/0 93 8
Die Wirksamkeit der Phosphonoalkanpolycarbonsäuren läßt sich auch in vivo leicht bei Ratten demonstrieren.The effectiveness of the phosphonoalkanepolycarboxylic acids can also be easily demonstrated in rats in vivo.
Dieser Test basiert auf der Beobachtung, daß hohe Dosierungen von Vitamin D^ eine starke Verkalkung in der Aorta und in den Nieren von Ratten hervorrufen. J>0 weibliche Ratten mit einem Gewicht von 15O - 200 g werden in drei Gruppen von je 10 Tieren aufgeteilt. Sie erhalten während der Testperiode eine normale Diät und Leitungswasser ad libitum. Eine Gruppe von 10 Tieren erhält keine weitere Behandlung. Eine zweite Gruppe der Tiere erhält vom J>. bis zum 7. Tag Je 75 000 Einheiten Vitamin D-, pro kg Körpergewicht durch eine Schlauchsonde. Die dritte Gruppe erhält ebenfalls vom 3. bis 7. Tag je 75 000 Einheiten Vitamin D-* und zusätzlich parenteral oder oral 10 mg pro kg Körpergewicht einer der beanspruchten Phosphonsäuren vom 1. bis 10. Tag. Nach 10 Tagen werden die Tiere getötet und ihre Aorten verascht, der Rückstand gelöst und das Calcium flammenphotometrisch bestimmt. Die erfindungsgemäß verwendeten Phosphonoalkanpolycarbonsäuren oder deren physiologisch unbedenklichen Salze reduzieren die Vitamin-D-*-induzierte Verkalkung der Aorten und Nieren erheblich.This test is based on the observation that high doses of vitamin D cause severe calcification in the aorta and kidneys of rats. J> 0 female rats weighing 150-200 g are divided into three groups of 10 animals each. You will be given a normal diet and tap water ad libitum during the trial period. A group of 10 animals received no further treatment. A second group of animals receives from the J>. Up to the 7th day 75,000 units of vitamin D per kg of body weight through a tube probe. The third group also receives 75,000 units of vitamin D- * from the 3rd to the 7th day and additionally 10 mg per kg of body weight parenterally or orally of one of the claimed phosphonic acids from the 1st to the 10th day. After 10 days, the animals are sacrificed and their aortas are incinerated, the residue is dissolved and the calcium is determined by flame photometry. The phosphonoalkanepolycarboxylic acids used according to the invention or their physiologically harmless salts reduce the vitamin D - * - induced calcification of the aortas and kidneys considerably.
Für die Herstellung von pharmazeutischen Präparaten in Form von Kapseln nach bekannten Methoden ist folgende Zusammensetzung des Kapselinhaltes unter Verwendung von erfindungsgemäßen Phosphonsäuren geeignet:The following composition is used for the production of pharmaceutical preparations in the form of capsules by known methods of the capsule contents using phosphonic acids according to the invention suitable:
Phosphonsäure 80 mgPhosphonic acid 80 mg
Stärke 19 mgStrength 19 mg
Natriumlaurylsulfat 1 mgSodium Lauryl Sulphate 1 mg
-Q--Q-
509826/0938509826/0938
Für die Herstellung von Tabletten eignet sich die folgende Formulierung:The following formulation is suitable for the production of tablets:
Phosphonsäure in Form desPhosphonic acid in the form of
Natriumsalzes 100 mgSodium salt 100 mg
Lactose 100 mgLactose 100 mg
Stärke 4? mgStrength 4? mg
Magnesiumstearat 3 mgMagnesium stearate 3 mg
Beispiel 4 Kosmetische Präparate Example 4 Cosmetic Preparations
Bei Verwendung der Phosphonsäure oder ihrer pharmazeutisch akzeptablen Salze in Mund- und Zahnpflegemitteln wird die Bildung von Zahnstein wesentlich reduziert. Der pH-Wert der erfindungsgemäßen Mundwasser oder Zahnpasten kann sich zwischen den Grenzen 5 bis 9 bewegen.When using phosphonic acid or its pharmaceutical acceptable salts in oral and dental care products, the formation of tartar is significantly reduced. The pH the mouthwash or toothpaste according to the invention can be move between limits 5 to 9.
Als Grundrezepturen für Zahnpasten sind folgende Formulierungen geeignet:The following formulations are the basic formulations for toothpastes suitable:
Glycerin Wasser Natriumcarboxymethylcellulose Kieselsäurexerogel Natriumlaurylsulfat Ätherische öle Süßstoff PhosphonsäureGlycerin water sodium carboxymethyl cellulose Silicic acid xerogel sodium lauryl sulfate Essential oils sweetener phosphonic acid
Glycerin Wasser Natriumcarboxymethylcellulose AIum1niumhydr oxi dGlycerine Water Sodium Carboxymethyl Cellulose Aluminum Hydroxide
- 10 5 0 9 8 2 6 / 0 9 3 8 - 10 5 0 9 8 2 6/0 9 3 8
AoAo
Natriuralaurylsulfat Kieselsäure pyrogen Ätherische öle Süßstoff PhosphonsäureSodium Lauryl Sulphate Silica Pyrogenic Essential Oils Phosphonic acid sweetener
Als Grundrezeptur für Mundwasser ist folgende Kombination geeignet:The following combination is the basic recipe for mouthwash suitable:
Äthylalkohol Glycerin Wasser Ätherische öle Natriumlaurylsulfat Antiseptixum (Chlorthymol) Süßstoff PhosphonsäureEthyl Alcohol Glycerin Water Essential Oils Sodium Lauryl Sulphate Antiseptixum (chlorothymol) Phosphonic acid sweetener
Durch den regelmäßigen Gebrauch der Zahnpasten und/oder Mundwasser mit einem Gehalt an Natriumsalzen der Phosphonsäure läßt sich die Bildung von Zahnstein wesentlich verringern und die Ausbildung von harten, kompakten Zahnbelägen wird weitgehend verhindert.Through regular use of toothpaste and / or mouthwash containing sodium salts of phosphonic acid the formation of tartar can be significantly reduced and the formation of hard, compact dental plaque largely prevented.
- 11 -- 11 -
509826/0938509826/0938
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2360798A DE2360798A1 (en) | 1973-12-06 | 1973-12-06 | Calcium deposition influencing pharmaceutical/cosmetic prepns. - contg. polymethylenephosphonic acid cpds. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2360798A DE2360798A1 (en) | 1973-12-06 | 1973-12-06 | Calcium deposition influencing pharmaceutical/cosmetic prepns. - contg. polymethylenephosphonic acid cpds. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2360798A1 true DE2360798A1 (en) | 1975-06-26 |
Family
ID=5900066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2360798A Withdrawn DE2360798A1 (en) | 1973-12-06 | 1973-12-06 | Calcium deposition influencing pharmaceutical/cosmetic prepns. - contg. polymethylenephosphonic acid cpds. |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2360798A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0298553A1 (en) * | 1987-07-06 | 1989-01-11 | Norwich Eaton Pharmaceuticals, Inc. | Methylene phosphonoalkylphosphinates, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| US4963681A (en) * | 1987-07-06 | 1990-10-16 | Norwich Eaton Pharmaceuticals, Inc. | Process for synthesis of aminomethylene phosphonoalkylphosphinates |
| FR2721929A1 (en) * | 1994-06-30 | 1996-01-05 | Centre Nat Rech Scient | STABLE, NON-HYDROLYZABLE ANALOGUES OF DIPHOSPHATES AND PROCESSES FOR PREPARING THE SAME |
-
1973
- 1973-12-06 DE DE2360798A patent/DE2360798A1/en not_active Withdrawn
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0298553A1 (en) * | 1987-07-06 | 1989-01-11 | Norwich Eaton Pharmaceuticals, Inc. | Methylene phosphonoalkylphosphinates, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| US4963681A (en) * | 1987-07-06 | 1990-10-16 | Norwich Eaton Pharmaceuticals, Inc. | Process for synthesis of aminomethylene phosphonoalkylphosphinates |
| US5574024A (en) * | 1987-07-06 | 1996-11-12 | Ebetino; Frank H. | Methylene phosphonoalkylphosphinates, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| FR2721929A1 (en) * | 1994-06-30 | 1996-01-05 | Centre Nat Rech Scient | STABLE, NON-HYDROLYZABLE ANALOGUES OF DIPHOSPHATES AND PROCESSES FOR PREPARING THE SAME |
| WO1996000733A1 (en) * | 1994-06-30 | 1996-01-11 | Centre National De La Recherche Scientifique | Diphosphate or triphosphate non-hydrolysable stable analogues and methods for their preparation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2343196C3 (en) | Aiacycloalkan-2 ^ -diphosphonic acids or their water-soluble salts | |
| DE2405254C2 (en) | Use of 3-amino-1-hydroxypropane-1, 1-diphosphonic acid or its water-soluble salts for influencing calcium metabolic disorders in the human or animal body | |
| DE2343147C2 (en) | Pyrrolidone-5,5-diphosphonic acids, their water-soluble salts, and processes for their preparation | |
| DE2343195C2 (en) | Cyclic aminophosphonic acids and processes for their preparation | |
| EP0001584B1 (en) | Hydroxydiphosphonic acids, process for their preparation and their use as complex-forming agents | |
| EP0175315B1 (en) | 4-dimethylamino-1-hydroxybutane-1,1-diphosphonic acid, its water soluble salts, process for their preparation and its use | |
| DE2360797C2 (en) | Pharmaceutical preparations | |
| DE69634357T2 (en) | FORMULATIONS WITH THE WATER-FREE MONONATRIUM SALT OF ALENDRONATE AND THEIR USE FOR THE TREATMENT OF BONE DISEASES | |
| DE2343197A1 (en) | PHARMACEUTICAL OR COSMETIC PREPARATIONS | |
| WO1988000590A1 (en) | Diphosphonium acid derivates and medicines containing the same | |
| DE2534391A1 (en) | 1-HYDROXY-3-AMINOALKANE-1,1-DIPHOSPHONIC ACIDS | |
| DE1908067B2 (en) | COMPOSITIONS FOR THE PREVENTION OF CALCULATION | |
| DE3201865A1 (en) | PHARMACEUTICAL PRODUCT AND THE USE THEREOF FOR THE TREATMENT OF OSTEOPATHY | |
| DE69818823T2 (en) | DIPOHOSPHONIC ACID SALTS FOR THE TREATMENT OF OSTEOPOROSIS | |
| DE2360798A1 (en) | Calcium deposition influencing pharmaceutical/cosmetic prepns. - contg. polymethylenephosphonic acid cpds. | |
| DE2328234C2 (en) | Agent suitable for systemic administration to inhibit the mobilization of calcium phosphate | |
| DE2513966C2 (en) | Piperidone-6,6-diphosphonic acid and process for its preparation | |
| DE2360711A1 (en) | Medicaments for controlling calcium depositon or dissolution - contg aminoalkane-phosphonic acids | |
| DE1900577B2 (en) | Orally administered agent to strengthen the mineralized bone and tooth tissue | |
| DE2716535C3 (en) | Use of D-Glucaro-1,5-lactam | |
| DE2226273C2 (en) | Preparations for the treatment of osteoporosis | |
| DE3240650C2 (en) | ||
| DE2446640A1 (en) | NEW GENTAMICIN DERIVATIVES, PROCESS FOR MANUFACTURING THE SAME AND CONTAINING ANTIBIOTIC COMPOSITIONS | |
| DE2360719A1 (en) | Prepns for controlling calcium deposition or dissolution - contg phosphonic acid derivs, for medical or cosmetic use | |
| DE10156617A1 (en) | Preparation of pure stereoisomers of tricyclo [5.2.1.0 ·· 2 ··. ·· 6 ··] -dec-9-yl-xanthate and medicinal products therefrom |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OD | Request for examination | ||
| 8130 | Withdrawal |