CN1153778C - Bile acid salts of metals with physiological action and the use thereof in therapy - Google Patents
Bile acid salts of metals with physiological action and the use thereof in therapy Download PDFInfo
- Publication number
- CN1153778C CN1153778C CNB971823979A CN97182397A CN1153778C CN 1153778 C CN1153778 C CN 1153778C CN B971823979 A CNB971823979 A CN B971823979A CN 97182397 A CN97182397 A CN 97182397A CN 1153778 C CN1153778 C CN 1153778C
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- Prior art keywords
- acid
- salt
- iron
- bile acide
- bile
- 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.)
- Expired - Fee Related
Links
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 7
- 239000002184 metal Substances 0.000 title claims abstract description 7
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 title abstract description 12
- 150000002739 metals Chemical class 0.000 title 1
- 238000002560 therapeutic procedure Methods 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 48
- 229910052742 iron Inorganic materials 0.000 claims description 24
- 210000000941 bile Anatomy 0.000 claims description 17
- 229960001661 ursodiol Drugs 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 claims description 7
- 239000004380 Cholic acid Substances 0.000 claims description 7
- 229960002471 cholic acid Drugs 0.000 claims description 7
- 235000019416 cholic acid Nutrition 0.000 claims description 7
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims description 7
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 claims description 6
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims description 6
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- DGABKXLVXPYZII-UHFFFAOYSA-N Hyodeoxycholic acid Natural products C1C(O)C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 DGABKXLVXPYZII-UHFFFAOYSA-N 0.000 claims description 3
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 3
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 229960001091 chenodeoxycholic acid Drugs 0.000 claims description 3
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- 239000010941 cobalt Substances 0.000 claims description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 3
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000010235 enterohepatic circulation Effects 0.000 claims description 3
- DGABKXLVXPYZII-SIBKNCMHSA-N hyodeoxycholic acid Chemical compound C([C@H]1[C@@H](O)C2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 DGABKXLVXPYZII-SIBKNCMHSA-N 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- 238000005907 ketalization reaction Methods 0.000 claims description 3
- 125000000468 ketone group Chemical group 0.000 claims description 3
- 229910052750 molybdenum Inorganic materials 0.000 claims description 3
- 239000011733 molybdenum Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229910052711 selenium Inorganic materials 0.000 claims description 3
- 239000011669 selenium Substances 0.000 claims description 3
- 239000011573 trace mineral Substances 0.000 claims description 3
- 235000013619 trace mineral Nutrition 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 235000009508 confectionery Nutrition 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052737 gold Inorganic materials 0.000 claims description 2
- 239000010931 gold Substances 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 229910052718 tin Inorganic materials 0.000 claims description 2
- 239000011135 tin Substances 0.000 claims description 2
- 229910052720 vanadium Inorganic materials 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000003716 cholic acid group Chemical group 0.000 claims 1
- 239000012050 conventional carrier Substances 0.000 claims 1
- 239000013589 supplement Substances 0.000 claims 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000003613 bile acid Substances 0.000 abstract 3
- 239000000203 mixture Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 150000002505 iron Chemical class 0.000 description 3
- 150000001457 metallic cations Chemical class 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 3
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical compound C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 2
- 206010022971 Iron Deficiencies Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- -1 alkali metal salt Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229940014499 ursodeoxycholate Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- IDVNITDXPCTHDK-UHFFFAOYSA-N 2-oxopropanedioic acid propanedioic acid Chemical compound O=C(C(=O)O)C(=O)O.C(CC(=O)O)(=O)O IDVNITDXPCTHDK-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229940009025 chenodeoxycholate Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000004222 ferrous gluconate Substances 0.000 description 1
- 235000013924 ferrous gluconate Nutrition 0.000 description 1
- 229960001645 ferrous gluconate Drugs 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- DKPMWHFRUGMUKF-KWXDGCAGSA-N hyocholic acid Chemical compound C([C@H]1[C@@H](O)[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 DKPMWHFRUGMUKF-KWXDGCAGSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000004673 intestinal mucosal barrier function Effects 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to bile acid metal salt with therapeutic activity, a medicinal compound containing the bile acid metal salt and a veterinary compound containing the bile acid metal salt.
Description
The present invention relates to have the bile acid salts of therapeutic activity.
The invention still further relates to the medical composition and the animal medicinal composition that contain described bile acid salts.
Have multiple metallic cation to play physiological action in vivo: except the iron as the oxyphorase component, trace elements such as the zinc of different content, copper, selenium, molybdenum, cobalt, manganese are that enzyme and physiological system enforcement normal function are necessary.These elements are normally by dietary ingestion, but for because the shortage of these elements that pathology or diet cause, just need by will suitable salt or the mixture administration to carry out medicine additional or diet is additional.
For iron, this problem is especially outstanding, often administration of iron need be treated hypoferric anemia.In order to treat sideropenia, using salt for example Ferrous Gluconate or ferrous sulfate or iron and succinylated proteic mixture at present.
Have been found that now above-mentioned bile acid salts can make metallic cation optionally in enterohepatic circulation inner height, absorption step by step.
Use bile acide to be proved to be effective especially, and can overcome and influence some of prior art compound defectives as the carrier of iron or trace element.
In fact the bile acide as the intestinal mucosal barrier permeability factor can provide high bioavailability, and this is because of their recirculation effects through enterohepatic circulation, and the progressively absorption dynamics that is therefore had.In addition, especially for molysite, use bile acide can avoid producing the common side effect that these compound oral administrations are brought as carrier, for example constipation, gastrointestinal reaction, abdomen rise, epigastric pain.
According to ordinary method, with natural bile acide or derivatives thereof and metal hydroxides reaction, perhaps an alkali metal salt or the alkaline earth salt with suitable metal-salt and bile acide carries out permutoid reaction, can make bile acid salts of the present invention.
The example of natural bile acide comprises cholic acid, Septochol, gallodesoxycholic acid, chenocholic acid, ursodesoxycholic acid, ursol cholic acid, hyodeoxycholic acid and corresponding ox sulphur (tauro-) and sweet ammonia conjugate (glyco-conjugates).
Can be randomly with natural bile acide derivatize, for example by with the anhydride reaction of di-carboxylic acid or polycarboxylic acid such as succsinic acid acid, pentanedioic acid acid, cyclohexane cyclohexanedimethanodibasic, introduce other salifiable acidic-group.
It is known that described derivative has some, and can make according to ordinary method, for example disclosed method in italian patent 1.163.090 number.
A kind of different methods is with the ketone group ketalization on the bile acide molecule, to use ketone group propanedioic acid (ketomalonic acid) with the Iocholic acid ketalization with tartrate.
When needing to increase the mol ratio of metallic cation/bile acide, on each bile acide molecule, exist to be easier to salifiable group and can to realize this point for treatment and application purpose.
According to the present invention, natural or semi-synthetic bile acide can be become salinization with being selected from following metal: iron (II), iron (III), copper (I), copper (II), zinc, cobalt, molybdenum, platinum, gold, manganese, vanadium, selenium, tin, nickel.
Especially preferably be used in the sideropenic ferrous salt of treatment or trivalent iron salt, especially trivalent iron salt in the humans and animals.
Use or other application for treatment, can be according to routine techniques, with vehicle [for example " Remington ' s pharmaceutical science handbook (Remington ' s PharmaceuticalSciences Handbook), Mack.Pub., N.Y., the vehicle of describing among the U.S.A.] bile acid salts of the present invention is mixed with pharmaceutical composition.
The example of described composition comprises capsule, tablet, syrup or drinkable solution, stomach is released and/or slow release formulation etc.Certainly, per daily dose depends on cationic type: for iron, the day dosage of bile acid salts of the present invention can be 100mg-3g, and every day, administration was 1-4 time.
In addition, bile acid salts of the present invention also can be included in diet formulation or human or the nutritional formulation for animals, and it can be optionally replenishes or any other component with useful activity is used with having.
Utilize following embodiment further to illustrate the present invention.
Embodiment 1
Preparation bile acide iron (II) salt
10g acid is dissolved in to contain small amounts of sodium hydroxide (=10%, be 20% for the bile acide that can discharge succinate), PH be in 8 the 7.5 volume water.
After the dissolving fully, 35 ℃ and stir under, with FeCl
36H
2The O aqueous solution is added in this mixture, wherein said FeCl
36H
2The O aqueous solution be by with 2.42g (for cholic acid or Felacrinos, for stoichiometry+10% excessive), 2.53g is (for gallodesoxycholic acid or ursodesoxycholic acid, for stoichiometry+10% excessive) or 5.02g (for the bile acide that can discharge succinate, for stoichiometry+10% excessive) trivalent iron salt is dissolved in lentamente, and 25ml water makes in advance.
The gained mixture is stirred to precipitation fully, and washing precipitation is until not containing muriate then.Productive rate: more than 95%.
The feature of gained salt is as described below:
Salt
Fusing point
Iron level
237-239 ℃ of 4.07-4.67 of cholic acid iron
(3 α, 7 α, 12 α-trihydroxy--5 β-ursodeoxycholic acid iron)
218-219 ℃ of 4.24-4.84 of Septochol iron
(3 α, 12 alpha-dihydroxy-s-5 β-ursodeoxycholic acid iron)
216-218 ℃ of 4.13-4.73 of Felacrinos iron
(3,7,12,5 β-triketocholanic acid iron)
Ferric chenodeoxycholate 214-218 ℃ 4.24-4.84
(3 α, 7 alpha-dihydroxy-s-5 β-ursodeoxycholic acid iron)
200 ℃ of 4.24-4.84 of ferric ursodeoxycholate
(3 α, 7 α ,-dihydroxyl-5 β-ursodeoxycholic acid iron)
193 ℃ of 4.24-4.84 of hyodeoxycholic acid iron
(3 α, 6 alpha-dihydroxy-s-5 β-ursodeoxycholic acid iron)
268-270 ℃ of 8.05-9.25 of two succinyl-ferric ursodeoxycholates
(biological 3 α that discharge succinate of energy, 7 alpha-dihydroxy-s-5 β-ursodeoxycholic acid iron)
Embodiment 2
Attached Fig. 1 and 2 represents, with 19.2mg iron/sky with the form of ferric ursodeoxycholate to two sideropenia patients administration after, the serum levels of iron content results that is obtained.
Claims (9)
- Bile acide be selected from the salt that following metal forms: iron (III), copper (I), copper (II), zinc, cobalt, molybdenum, platinum, gold, manganese, vanadium, selenium, tin, nickel.
- 2. the salt of claim 1, wherein said metal is iron (III).
- 3. each salt of claim 1-2, wherein said bile acide is selected from cholic acid, Septochol, gallodesoxycholic acid, chenocholic acid, ursol cholic acid, ursodesoxycholic acid, hyodeoxycholic acid and corresponding ox sulphur and sweet ammonia conjugate.
- 4. the salt of claim 1-3, but wherein introduced other salt forming group that is selected from di-carboxylic acid or polycarboxylic acid on the cholic acid.
- 5. the salt of claim 4, wherein said di-carboxylic acid or polycarboxylic acid are succsinic acid, pentanedioic acid, cyclohexane cyclohexanedimethanodibasic.
- 6. each salt of claim 1-3, wherein with tartrate with arbitrary ketone group ketalization.
- 7. each salt or bile acide ferrous salt of claim 1-6 is used for application in the medicine of enterohepatic circulation trace element supplement in preparation.
- 8. each molysite of claim 1-6 is used for the application of the medicine of iron treatment in preparation.
- 9. contain significant quantity at least a as each described salt of claim 1-6 as active ingredient, and the pharmaceutical composition of conventional carrier and vehicle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB971823979A CN1153778C (en) | 1997-10-09 | 1997-10-09 | Bile acid salts of metals with physiological action and the use thereof in therapy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB971823979A CN1153778C (en) | 1997-10-09 | 1997-10-09 | Bile acid salts of metals with physiological action and the use thereof in therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1275989A CN1275989A (en) | 2000-12-06 |
| CN1153778C true CN1153778C (en) | 2004-06-16 |
Family
ID=5178451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB971823979A Expired - Fee Related CN1153778C (en) | 1997-10-09 | 1997-10-09 | Bile acid salts of metals with physiological action and the use thereof in therapy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1153778C (en) |
-
1997
- 1997-10-09 CN CNB971823979A patent/CN1153778C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1275989A (en) | 2000-12-06 |
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