US20100068273A1 - Pharmaceutical formulation, its use, and method for its manufacture - Google Patents

Pharmaceutical formulation, its use, and method for its manufacture Download PDF

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US20100068273A1
US20100068273A1 US12616829 US61682909A US20100068273A1 US 20100068273 A1 US20100068273 A1 US 20100068273A1 US 12616829 US12616829 US 12616829 US 61682909 A US61682909 A US 61682909A US 20100068273 A1 US20100068273 A1 US 20100068273A1
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calcium
formulation
pharmaceutical
dry
plant
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US12616829
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Michael A. Popp
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Bionorica AG
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Bionorica AG
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2813Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/42Cucurbitaceae (Cucumber family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736Prunus, e.g. plum, cherry, peach, apricot or almond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/85Verbenaceae (Verbena family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/889Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus

Abstract

A pharmaceutical formulation of a calcium salt and a dry plant extract in the form of a coated tablet, in which the formulation has a core of at least one dry plant extract, enveloped by at least one coating of at least one calcium salt. The plant extracts for the core may be selected from: Vitex agnus castus (chaste tree); Belamcanda chinensis (leopard lily); Cimicifuga racemosa (black cohosh); Trifolium pratense L. (purple trefoil); Oenothera biennis hom. (primrose); Glycine soja (soy bean); Serenoa repens (saw-palmetto); Urtica dioica (stinging nettle), in particular its root; Cucurbita pepo (pumpkin), in particular its seed; Pygeum africanum; as well as suitable mixtures of these. Methods for the use of the formulation in treating osteoporosis and for manufacturing the formulation are provided.

Description

    FIELD OF THE INVENTION
  • [0001]
    The present invention relates to a pharmaceutical formulation of a calcium salt and a dry plant extract, its use in the treatment of osteoporosis, and a method for its manufacture.
  • BACKGROUND TO THE INVENTION
  • [0002]
    17β-estradiol, which is naturally formed in the ovaries [also referred to as E2], has a general proliferation-enhancing action in humans and animals. In addition to controlling the female cycle, it has, i. a., a homeostatic effect on the metabolism of the bone, while also preventing the formation of atherotic plaques on vessel endothelia.
  • [0003]
    During menopause, estradiol levels decrease due to cessation of ovarial function. In the absence of sufficiently high estradiol levels in the blood, the activity of the osteoclasts, and thus breakdown of the bone mass—so-called “osteoporosis”—predominates in the bone tissue, which is accompanied by an increased risk of skeletal breakage.
  • [0004]
    In recent times it was found that this syndrome of osteoporosis brought about by lack of sexual hormone is not restricted to women, but that from a certain advanced age, osteoporosis brought about by lack of sexual hormone also occurs in men, in particular in connection with ailments of the prostate.
  • [0005]
    The classical prophylaxis and therapy in woman consists in supplementing natural estrogen by administration of natural and synthetic estrogens. In particular, for prophylactic purposes, calcium doses of approx. 1 gram of calcium per day are applied in man and woman.
  • [0006]
    Administration of estrogens such as, e. g., 17β-estradiol or the chemical derivatives thereof is, however, accompanied by the known grave side effects of uterotrophic effect, increased risk of thrombo-embolism, weight gain, and the like.
  • [0007]
    There have been many attempts reported in the prior art to find medicaments capable of producing an estrogen-type effect either without undesireable side effects, or with strongly diminished undesirable side effects. Plant extracts have been frequently used that exhibit the desired action of osteoporosis prophylaxis, but not, however, the undesirable uterotrophic effects.
  • [0008]
    Thus, for example, WO 99/47149 (=EP 1064009A1) to the present applicant discloses that extracts from iridaceae, in particular from Cimicifuga racemosa and Belamcanda chinensis and of the isoflavonoid tectorigenin contained therein, do not have an estrogen-type effect on the uterus, yet do so in the hypothalamo-hypophysary axis, in the cardiovascular system, and in the bone, so that these plant extracts may be employed for the prophylaxis and therapy of osteoporosis.
  • [0009]
    Moreover, calcium preparations for the prophylaxis of osteoporosis are known in the prior art. A pharmaceutical formulation to this end, besides an injection solution, is preferably an effervescent tablet for oral application. Such effervescent tablets may, e. g., have the following composition:
  • [0010]
    Tablets with 500 mg of Ca2+: 1250 mg of calcium carbonate, 2050 mg of citric acid, further constituents: lactose 1H2O, macrogol 6000, Povidon, sodium cyclamate, saccharine sodium 2H2O, Dimeticon 350, highly dispersed silica, macrogol stearate 400, sorbic acid, flavoring agents.
  • [0011]
    Tablets with 1000 mg of Ca2+: 4954 mg of calcium lactogluconate, 900 mg of calcium carbonate, and further constituents: citric acid, sodium cyclamate, saccharine sodium, mannitol, macrogol 4000, sodium hydrogencarbonate, flavoring agents.
  • [0012]
    In order to spare patients multiple applications, and also for cost reasons, a combination of calcium preparations having a high Ca2+ content with dry plant extract having an anti-osteoporosis effect would be desirable.
  • [0013]
    Simple admixture to a calcium effervescent tablet mass, however, is foiled by the high sensitivity of the dry extracts to acids in an aqueous medium on the one hand, and by the poor water solubility of many dry extracts in an acidic medium on the other hand. Moreover the humidity-sensitive effervescent masses are imperiled by the highly hygroscopic dry extracts.
  • [0014]
    Encapsulation in customary gelatin capsules must equally be ruled out as the capsules are generally not water vapor tight and thus would decompose and/or agglomerate the dry plant extract, so that the pharmaceutical quality would cease to be ensured due to undefined bioavailability, release, and/or effectivity. Moreover the stability of such gelatin capsules is not warranted, for it is reported in literature, e. g., that instances of crosslinking with the gelatin occur when plant extracts are encapsulated in gelatin, and significant changes of the ingredients result from water absorption by the dry extract.
  • [0015]
    Thus, for example, a sugar-coated tablet, or dragée, formulation consisting of a mixture of calcium and dry plant extract would be optimal. As was mentioned above, significant calcium contents of 500 mg Ca2+ and more, together with the relatively large amounts of auxiliaries for dragée manufacture, would result in large dragée sizes and weights which would not be acceptable to patients.
  • [0016]
    Known solid formulations are combination preparations of calcium with vitamin D3 in the form of chewing tablets, e. g. as Ossofortin® forte chewing tablets by the company Strathmann AG+Co., Sellhopsweg 1, D-22459 Hamburg.
  • [0017]
    Such chewing tablets for supportive treatment of osteoporosis have the following composition:
  • [0018]
    1500.3 mg of calcium carbonate (corresponding to 600 mg of Ca++), Colecalciferol dry concentrate (100 000 I.U./g) 400 I.U., further constituents: xylitol, corn starch, saccharine sodium, flavoring agent, magnesium stearate.
  • [0019]
    Up to the present, no prior art has taught the combination of calcium preparations with plant extracts suited for the above described prophylaxis and/or therapy of osteoporosis, for the above named reasons.
  • SUMMARY OF THE INVENTION
  • [0020]
    Accordingly it is an object of the present invention to furnish a pharmaceutical formulation combining both the advantages of calcium substitution and—where necessary—vitamin D3 substitution, and the advantages of a dry plant extract for the prophylaxis and/or treatment of osteoporosis.
  • [0021]
    This object is attained through a pharmaceutical formulation of a calcium salt and a dry plant extract, its use in the treatment of osteoporosis, and a method for its manufacture.
  • [0022]
    The invention in particular concerns a pharmaceutical formulation of a calcium salt and a dry plant extract, wherein the pharmaceutical formulation includes an inner pressed body of at least one dry plant extract enveloped by at least one coating of at least one calcium salt.
  • [0023]
    Through the pharmaceutical formulation of the invention it is possible for the first time to furnish combinations that are sensible in terms of quantities, of dry plant extracts effective against osteoporosis, such as, for example, Cimicifuga racemosa, Belamcanda chinensis, Vitex agnus castus or Urtica dioica radix, and their mixtures, with calcium. Here it is particularly advantageous that the coating—other than customary in the prior art—consists of auxiliaries, but essentially contains active agent, i.e., calcium, exclusively.
  • DETAILED DESCRIPTION
  • [0024]
    For the manufacture of the dry plant extracts, the present applicant's PCT application WO 99/47149 is incorporated in its entirety by reference. In addition to the solvents mentioned there, however, it is furthermore possible to extract the plants in question with mixtures of organic-aqueous solvents, exclusively aqueous, or also with the aid of supercritical CO2 (e. g. in the case of Serenoa repens).
  • [0025]
    By the present pharmaceutical formulation it is achieved that the generally highly hygroscopic plant extracts usually formulated by addition of water-binding auxiliaries e. g. to dragees or film tablets, may be made available with a low mass and small volume, embedded in a coat of an inert active principle having a protective effect against humidity in the form of a calcium salt.
  • [0026]
    As a result, an extremely favorable ratio of dry plant extract to calcium to auxiliaries is obtained, so that it is partly even possible to entirely omit auxiliaries, with the exception of small amounts of lubricants.
  • [0027]
    Thus it is for the first time possible to furnish a combination preparation of a dry plant extract, calcium salts and—where necessary—also vitamin D3, which has a calcium content whereby the approximately 1000 mg of Ca2+ ions p.d. required for prophylaxis and/or therapy may be achieved without administration of additional calcium preparations.
  • [0028]
    A preferred embodiment of the present invention is characterized in that in the calcium-containing coating and/or in the inner dry plant extract pressed body it additionally contains cholecalciferols, in particular Colecalciferol (vitamin D3).
  • [0029]
    Moreover the pharmaceutical formulation may in addition contain at least one fluoride salt, in particular sodium fluoride, wherein it is preferred for the fluoride salt to be present in the inner pressed body.
  • [0030]
    Preferably the pharmaceutical formulation is characterized in that the dry plant extract is selected from the group consisting of extracts from: Vitex agnus castus (chaste tree); Belamcanda chinensis (leopard lily/blackberry lily); Cimicifuga racemosa (black cohosh); Trifolium pratense L. (purple trefoil); Oenothera biennis hom. (primrose); Glycine soja (soy bean); Serenoa repens (saw-palmetto); Urtica dioica (stinging nettle), in particular its root; Cucurbita pepo (pumpkin), in particular its seed; Pygeum africanum; as well as suitable mixtures of these.
  • [0031]
    In a preferred embodiment of the pharmaceutical formulation of the invention, the calcium salt is selected from the group consisting of calcium carbonates; calcium hydrogen carbonates; calcium halides, in particular calcium chlorides and calcium iodides; calcium phosphates; calcium hydrogen phosphates, in particular calcium monohydrogen phosphate; dicalcium hydrogen phosphates, calcium lactates; calcium lactonates; calcium succinates; calcium tartrates; calcium gluconates; others; as well as suitable mixtures of the above.
  • [0032]
    The preferred pharmaceutical formulation in accordance with the present invention is a coated tablet, wherein the coating is a pressed body of at least one calcium salt, and the core is a pressed body of at least one of the named dry plant extracts, wherein vitamin D3 may in addition be contained in the core.
  • [0033]
    The pharmaceutical formulation may, however, also be a dot tablet (bull-eye tablet) in which the core, although still entirely enveloped by the coating, nevertheless need not be centered inside the coating.
  • [0034]
    It is furthermore possible in the present pharmaceutical formulation to form the coating of a plurality of calcium layers, wherein preferably each layer contains a different calcium salt.
  • [0035]
    A preferred pharmaceutical formulation has, e. g., a calcium content of approx. 50 to 1000 mg per coated tablet and a dry plant extract content of approx. 0.5 to 100 mg. Hereby it is possible through one to three administrations per day, which is agreeable for the patient, to supply the entire recommended daily dose of Ca2+ ions of approx. 1000 mg of Ca2+ with simultaneous administration of the required phytoextracts having an anti-osteoporosis action and of vitamin D3.
  • [0036]
    Moreover a preferred pharmaceutical formulation may have a polymer film as an external envelope, whereby the swallowing property and the esophageal sliding property may be improved. Moreover the polymer film may prevent dust abrasion and the penetration of humidity into the coating. Such a polymer envelope is, however, not essential.
  • [0037]
    The pharmaceutical formulation of the present invention requires few auxiliaries or even none at all. Where necessary, however, the auxiliaries customary in galenics, for example disintegrants, in particular on the basis of starches and/or their derivatives; binders, in particular microcrystalline cellulose, gum arabic; lubricants, in particular stearic acid and/or magnesium stearate; as well as slip agents, in particular polyethylene glycol, and the like may be used.
  • [0038]
    Preferably the pharmaceutical formulations of the invention are suited as medicaments for the treatment of osteoporosis of various geneses, and in a particularly preferred manner for the prophylaxis and/or therapy of osteoporoses brought about by lack of sexual hormone in women and men of advanced age.
  • [0039]
    Manufacture of the pharmaceutical formulations of the invention takes place in accordance with the following principle:
  • [0040]
    Initially a pressed body core is produced from a dry plant extract, wherein the dry plant extract is selected from the group consisting of: Vitex agnus castus (chaste tree); Belamcanda chinensis (leopard lily); Cimicifuga racemosa (black cohosh); Trifolium pratense L. (purple trefoil); Oenothera biennis hom. (primrose); Glycine soja (soy bean); Serenoa repens (saw-palmetto); Urtica dioica (stinging nettle), in particular its root; Cucurbita pepo (pumpkin), in particular its seed; Pygeum africanum; as well as suitable mixtures of these.
  • [0041]
    This core is transferred onto a first partial quantity of a coating mixture of at least one calcium salt, subsequently filling is performed with a second partial quantity of the coating mixture; and the entire formulation of the core and the two partial quantities of calcium salt-containing coating mixture is pressed to form the pharmaceutical formulation. The calcium salt is selected from the group consisting of:
  • [0042]
    calcium carbonates; calcium hydrogen carbonates; calcium halides, in particular calcium chlorides and calcium iodides; calcium phosphates; calcium hydrogen phosphates, in particular calcium monohydrogen phosphate; dicalcium hydrogen phosphates, calcium lactates; calcium lactonates; calcium succinates; calcium tartrates; calcium gluconates; others; as well as suitable mixtures of these.
  • [0043]
    Preferably the core is substantially centered on the first partial quantity of the coating mixture, whereby a so-called coated tablet is obtained. It is, however, also possible to manufacture so-called bull-eye-tablets (dot tablets) having a core which is not centered, however enveloped, and in which the core may be partly visible through the coating.
  • [0044]
    For pressing tablets, commercially available tablet presses may be used, such as those of the companies FETTE, KORSCH and KILIAN. Particularly suited, for example, is a synchronously operating double-sided rotary press by the company MANESTY. In the double-sided rotary press, the cores are produced on the one tower of the rotary press and transferred by the intermediate transferring and centering mechanism to the tower of the second rotary press, where press-application of the coating takes place.
  • [0045]
    More basically, the pharmaceutical formulations of the present invention may, however, also be carried out with two rotary presses, where the cores are pressed in one of them, while press-application of the coating takes place in the second one.
  • [0046]
    The advantage for the manufacture of the coated tablets of the invention as a pharmaceutical formulation with the aid of a double-sided rotary press, however, resides in the fact that the cores may be pre-pressed in the first tower of the press so as to be comparatively soft. Final compression in the second tower of the double-sided rotary press thus results in very good adhesion between dry plant extract core and calcium coating.
  • [0047]
    A coated tablet manufactured in this manner has, for example, the following composition:
  • [0000]
    Coating: CaCO3 1250 mg
    (corr. to 500 mg of Ca2+)
    vitamin D3 200 I.U.
    Core: Cimicifuga racemosa 20 mg
    (dry extract preparation)
    Auxiliaries: magnesium stearate 8 mg
    stearic acid 4 mg
    microcrystalline cellulose 40 mg
    gum arabic 50 mg
  • [0048]
    The exemplary coated tablet combines the advantages of oral calcium and vitamin D3 substitution with the required dose of Cimicifuga racemosa dry extract. By oral application of no more than 2 tablets daily, the dose recommended for the prophylaxis and/or therapy of osteoporosis of calcium and vitamin D3 dose of approx. 1000 mg of Ca2+ p.d., or 400 I.U. of vitamin D3, as well as the desired simultaneous administration of 40 mg of Cimicifuga racemosa dry extract is achieved.
  • [0049]
    It is, of course, also possible and advantageous to manufacture the dry extract core from other of the named phyto-extracts or from mixtures of different extracts depending on the constellation of indications. Thus, e. g., a coated tablet of the invention, adjusted for ailments of the prostate, may contain a Serenoa repens extract in the core.

Claims (25)

  1. 1. A pharmaceutical formulation of a calcium salt and a dry plant extract, comprising an inner pressed body of at least one dry plant extract, which is enveloped by at least one calcium-containing coating.
  2. 2. The pharmaceutical formulation in accordance with claim 1, wherein the dry plant extract is selected from the group consisting of extracts from: Vitex agnus castus (chaste tree); Belamcanda chinensis (leopard lily); Cimicifuga racemosa (black cohosh); Trifolium pratense L. (purple trefoil); Oenothera biennis hom. (primrose); Glycine soja (soy bean); Serenoa repens (saw-palmetto); Urtica dioica (stinging nettle); Cucurbita pepo (pumpkin); Pygeum africanum; and suitable mixtures thereof.
  3. 3. The pharmaceutical formulation in accordance with claim 2, wherein the dry plant extract is selected from the group consisting of extracts from: Urtica dioica (stinging nettle) root; Cucurbita pepo (pumpkin) seed; and suitable mixtures thereof.
  4. 4. The pharmaceutical formulation in accordance with claim 1, wherein the calcium salt is selected from the group consisting of: calcium carbonates; calcium hydrogen carbonates; calcium halides; calcium phosphates; calcium hydrogen phosphates; dicalcium hydrogen phosphates; calcium lactates; calcium lactonates; calcium succinates; calcium tartrates; calcium gluconates; and suitable mixtures thereof.
  5. 5. The pharmaceutical formulation in accordance with claim 4, wherein the calcium salt is selected from the group consisting of: calcium chlorides; calcium iodides; calcium monohydrogen phosphate; and suitable mixtures thereof.
  6. 6. The pharmaceutical formulation in accordance with claim 1, wherein said formulation is a coated tablet, said coating is a pressed body of at least one calcium salt, and said core is a pressed body of at least one dry plant extract.
  7. 7. The pharmaceutical formulation in accordance with claim 1, wherein said formulation is a dot tablet (bull-eye tablet).
  8. 8. The pharmaceutical formulation in accordance with claim 1, wherein the coating comprises a plurality of calcium layers.
  9. 9. The pharmaceutical formulation in accordance with claim 8, wherein each said layer contains a different calcium salt.
  10. 10. The pharmaceutical formulation in accordance with claim 6, wherein said formulation has a calcium content of about 50 to about 1000 mg per coated tablet and a dry plant extract content of about 0.5 to about 100 mg.
  11. 11. The pharmaceutical formulation in accordance with claim 1, wherein said formulation further comprises a polymer film as an external envelope.
  12. 12. The pharmaceutical formulation in accordance with claim 6, wherein said formulation has a calcium content of about 1250 mg of calcium carbonate (corresponding to about 500 mg of Ca2+) and about 200 I.U. vitamin D3 in the coating of the coated tablet, and about 20 mg dry extract preparation of Cimicifuga racemosa in the core of the coated tablet.
  13. 13. The pharmaceutical formulation in accordance with claim 1, wherein said calcium-containing coating and/or said inner pressed body of dry plant extract formulation further comprises one or more cholecalciferols.
  14. 14. The pharmaceutical formulation in accordance with claim 13, wherein said cholecalciferol is Colecalciferol (vitamin D3).
  15. 15. The pharmaceutical formulation in accordance with claim 19, wherein said formulation further comprises at least one fluoride salt.
  16. 16. The pharmaceutical formulation in accordance with claim 15, wherein said fluoride salt is sodium fluoride.
  17. 17. The pharmaceutical formulation in accordance with claim 15, wherein said fluoride salt is present in the inner pressed body.
  18. 18. The pharmaceutical formulation in accordance with claim 11, wherein said formulation further comprises one or more auxiliaries selected from the group consisting of disintegrants, binders, lubricants, and slip agents.
  19. 19. The pharmaceutical formulation in accordance with claim 18, wherein said formulation is selected from the group consisting of a starch, a starch derivative, a microcrystalline cellulose, gum arabic, stearic acid, magnesium stearate, polyethylene glycol, and a mixture thereof.
  20. 20. A method for the treatment or prevention of osteoporoses of various geneses, said method comprising administering to a subject in need thereof an effective amount of the formulation of claim 1.
  21. 21. The method in accordance with claim 20, wherein said osteoporoses of various geneses are brought about by lack of sexual hormone, by a hormone-related geriatric complaint, by a menopausal complaint, by a prostate affliction, by an accompanying cardiovascular disorder, by a disturbances of lipid metabolism, by a disorder accompanying a calcium deficiency, or by a combination thereof.
  22. 22. A method for manufacturing a pharmaceutical formulation in accordance with claim 1, said method comprising:
    preparing a pressed body core of a dry plant extract, wherein the dry plant extract is selected from the group consisting of extracts from: Vitex agnus castus (chaste tree); Belamcanda chinensis (leopard lily); Cimicifuga racemosa (black cohosh); Trifolium pratense L. (purple trefoil); Oenothera biennis hom. (primrose); Glycine soja (soy bean); Serenoa repens (saw-palmetto); Urtica dioica (stinging nettle); Cucurbita pepo (pumpkin); Pygeum africanum; and suitable mixtures thereof;
    transferring said core to a first partial quantity of a coating mixture of at least one calcium salt, followed by filling with a second partial quantity of the coating mixture; and
    pressing the entire formulation comprised of the core and the two partial quantities of the calcium salt-containing coating mixture to form the pharmaceutical formulation;
    wherein the calcium salt is selected from the group consisting of:
    calcium carbonates; calcium hydrogen carbonates; calcium halides; calcium phosphates; calcium hydrogen phosphates; dicalcium hydrogen phosphates, calcium lactates; calcium lactonates; calcium succinates; calcium tartrates; calcium gluconates; and suitable mixtures thereof.
  23. 23. The method in accordance with claim 22, wherein the core is centered on the first partial quantity of the coating mixture.
  24. 24. The method in accordance with claim 23, wherein the pharmaceutical formulation further comprises one or more auxiliaries selected from the group consisting of disintegrants, binders, lubricants, and slip agents.
  25. 25. The method in accordance with claim 24, wherein said formulation is selected from the group consisting of a starch, a starch derivative, a microcrystalline cellulose, gum arabic, stearic acid, magnesium stearate, polyethylene glycol, and a mixture thereof.
US12616829 2001-06-08 2009-11-12 Pharmaceutical formulation, its use, and method for its manufacture Abandoned US20100068273A1 (en)

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Application Number Priority Date Filing Date Title
DE2001127897 DE10127897B4 (en) 2001-06-08 2001-06-08 Coated tablet with plant dry extracts
DE10127897.7 2001-06-08
US10480078 US7629005B2 (en) 2001-06-08 2002-04-10 Pharmaceutical formulation consisting of a plant dry extract with a calcium coating
PCT/EP2002/004002 WO2002100422A1 (en) 2001-06-08 2002-04-10 Pharmaceutical formulation consisting of a plant dry extract with a calcium coating
US12616829 US20100068273A1 (en) 2001-06-08 2009-11-12 Pharmaceutical formulation, its use, and method for its manufacture

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110045014A1 (en) * 2006-02-17 2011-02-24 Hideaki Matsuda Acceleration agent of calcium absorption
US9486489B2 (en) 2011-08-19 2016-11-08 Bionorica Se Method for producing dry extracts

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10127897B4 (en) 2001-06-08 2006-04-20 Bionorica Ag Coated tablet with plant dry extracts
US6767560B2 (en) * 2002-01-22 2004-07-27 Paul H Paek Fabrication method of oral care composition
US7198653B2 (en) 2003-07-31 2007-04-03 Delavau Llc Calcium carbonate granulation
US20050238739A1 (en) * 2004-04-23 2005-10-27 Thomas Nisslein Composition comprising a combination of calcium, cimicifugae racemosae rhizoma and vitamin D and its use as a pharmaceutical in conditions or disorders associated with or resulting from calcium deficiency or as a nutritional supplement
US20060039971A1 (en) * 2004-08-19 2006-02-23 Lee Robert E Effervescent composition including alternative hormone replacement therapy agent
EP1745796A1 (en) * 2005-07-19 2007-01-24 Bionorica Research GmbH Compound preparation for treating prostate carcinoma
FR2893848B1 (en) * 2005-11-28 2011-11-11 Physcience phytohormonale composition and its use as hormone replacement
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US9138414B1 (en) 2006-09-15 2015-09-22 Delavau Llc Calcium supplement having enhanced absorption
US8221803B1 (en) 2007-06-25 2012-07-17 OncoNatural Solutions, Inc. Composition for prostate health
DE102008012988A1 (en) 2008-03-07 2009-09-10 S.W. Patentverwertungs Ltd. Composition and uses for affecting hair growth
EP2545932A1 (en) 2011-07-12 2013-01-16 Bionorica Se Selected cimicifuga fractions for treating osteoporosis
WO2013007807A1 (en) 2011-07-12 2013-01-17 Bionorica Se Selected cimicifuga fractions for the treatment of osteoporosis
WO2013074046A1 (en) 2011-08-08 2013-05-23 Mahmut Bilgic Pharmaceutical formulations comprising isoflavone
EP2559438A1 (en) 2011-08-19 2013-02-20 Bionorica Se Method for manufacturing dry extracts
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EP2606902A1 (en) 2011-12-19 2013-06-26 Bionorica SE Rhus copallina extract as medicine
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EP2810650A1 (en) * 2013-06-06 2014-12-10 Bionorica Se Medicament comprising thyme and primrose or thyme and ivy as PDE-4 inhibitor
JP2014237608A (en) * 2013-06-07 2014-12-18 株式会社日本食品薬化 Estrogenic agent, melanogenesis inhibitory agent, external preparation for skin, and food and drink for cosmetic use
JPWO2015020191A1 (en) * 2013-08-09 2017-03-02 日東薬品工業株式会社 Calcium agent
EP3206701A1 (en) 2014-10-17 2017-08-23 Bionorica SE Canephron for treatment of prostatitis

Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6444218B1 (en) *
US2410417A (en) * 1944-03-04 1946-11-05 Lever Brothers Ltd Vitamin and mineral dietary supplement and method of making
US3030273A (en) * 1959-09-02 1962-04-17 Abbott Lab Plastic tablet coating
US3345265A (en) * 1963-10-09 1967-10-03 Kendall & Co Multiple layer tablet with calcium salt central core separated from soluble fluoride outer coating
US4729895A (en) * 1983-02-22 1988-03-08 Teijin Limited Composition for solid pharmaceutical preparations of active vitamins D.sub.3
US4915948A (en) * 1987-08-31 1990-04-10 Warner-Lambert Company Tablets having improved bioadhesion to mucous membranes
US4996061A (en) * 1987-10-07 1991-02-26 Merrell Dow Pharmaceuticals Inc. Pharmaceutical composition for piperidinoalkanol-decongestant combination
US5093130A (en) * 1989-09-26 1992-03-03 Plant Genetics Powder coated hydrogel capsules
US5569459A (en) * 1995-02-15 1996-10-29 Bio-Virus Research Incorporated Pharmaceutical compositions for the management of premenstrual syndrome and alleviation of menopausal disorders
US5948443A (en) * 1996-02-23 1999-09-07 Medical Doctor's Research Institute, Inc. Acetylsalicylic acid and micronutrient supplementation for nutritional losses and coronary heart disease
US6004558A (en) * 1998-02-25 1999-12-21 Novogen, Inc. Methods for treating cancer with legume plant extracts
WO2000018415A1 (en) * 1998-09-30 2000-04-06 Hexal Ag Pharmaceutically active plant preparation for the treatment of migraine
US6139872A (en) * 1996-08-14 2000-10-31 Henkel Corporation Method of producing a vitamin product
US6200594B1 (en) * 1999-12-29 2001-03-13 Vital Dynamics, Inc. Breast-enhancing, herbal compositions and methods of using same
US6267994B1 (en) * 1996-12-14 2001-07-31 Schaper & Bruemmer Gmbh & Co. Kg Use of extract of cimicifuga racemosa
US20010036468A1 (en) * 1998-07-25 2001-11-01 Sam-A-Pharmaceuticals Co., Ltd. Soft chewable multivitamin tablet comprising separated active ingredients
US20030185905A1 (en) * 1997-05-06 2003-10-02 Roman Conrad Muhlbauer Plant extracts for the treatment of increased bone resorption

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4681766A (en) 1986-01-07 1987-07-21 Warner-Lambert Company Coatings for chewing gums containing gum arabic and a soluble calcium salt
US4752479A (en) * 1986-05-27 1988-06-21 Ciba-Geigy Corporaton Multi vitamin and mineral dietary supplement with controlled release bioavailable iron
EP0610060A1 (en) 1993-02-01 1994-08-10 Conrad Gorinsky Bisbenzylisoquinoline derivatives
DE4431653C2 (en) 1994-09-06 2000-01-20 Lohmann Therapie Syst Lts The coated tablet for controlled release of active substances, a process for their preparation and their use
JPH0930977A (en) * 1995-07-20 1997-02-04 Shigetoshi Kadota Therapeutic agent for bone disease containing extract of black cohosh root
CA2271683C (en) 1997-09-09 2007-11-27 Select Release, L.C. Coated particles, methods of making and using
CN1179972A (en) 1997-09-29 1998-04-29 杨成玉 Multifunctional effervescent for cleaning mouth
US20050037100A1 (en) 1998-03-19 2005-02-17 Bionorica Ag Utilization of extracts from iris plants, cimicifuga racemose and tectorigenin as an estrogen-like organ-selective medicament without uterotropic
DE19812204A1 (en) * 1998-03-19 1999-11-04 Plantamed Arzneimittel Gmbh Use of extracts from Cimicifuga racemosa and Belamcanda sinensis as estrogenartiges organ selective drugs without a uterotrophic effect
DE19814905A1 (en) * 1998-04-02 1999-10-07 Michael O Ruepp Aar Pharma Use of bearberry leaves (Arctostaphylos uva ursi) -, birch leaves (Betula) -, horsetail (Equisetum) - and nettle (Urtica) extracts
US6444018B1 (en) * 1998-06-25 2002-09-03 Xerox Corporation Phase change ink carrier compositions containing anhydride/amino alcohol-based adducts
GB9813906D0 (en) * 1998-06-26 1998-08-26 Isis Innovations Ltd Coatings
WO2000006127A1 (en) * 1998-07-30 2000-02-10 Warner-Lambert Company Centerfill delivery system for nutraceuticals
GB9821670D0 (en) 1998-10-05 1998-12-02 Muhlbauer Roman C Plant extracts for the treatment of increased bone resorption
GB9825033D0 (en) * 1998-11-13 1999-01-13 Nycomed Pharma As Process
CA2352542C (en) 1998-11-24 2009-05-19 Steigerwald Arzneimittelwerk Gmbh Method for producing medicaments from plant extracts, in a solid form of administration
DE10127897B4 (en) 2001-06-08 2006-04-20 Bionorica Ag Coated tablet with plant dry extracts

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6444218B1 (en) *
US2410417A (en) * 1944-03-04 1946-11-05 Lever Brothers Ltd Vitamin and mineral dietary supplement and method of making
US3030273A (en) * 1959-09-02 1962-04-17 Abbott Lab Plastic tablet coating
US3345265A (en) * 1963-10-09 1967-10-03 Kendall & Co Multiple layer tablet with calcium salt central core separated from soluble fluoride outer coating
US4729895A (en) * 1983-02-22 1988-03-08 Teijin Limited Composition for solid pharmaceutical preparations of active vitamins D.sub.3
US4915948A (en) * 1987-08-31 1990-04-10 Warner-Lambert Company Tablets having improved bioadhesion to mucous membranes
US4996061A (en) * 1987-10-07 1991-02-26 Merrell Dow Pharmaceuticals Inc. Pharmaceutical composition for piperidinoalkanol-decongestant combination
US5093130A (en) * 1989-09-26 1992-03-03 Plant Genetics Powder coated hydrogel capsules
US5569459A (en) * 1995-02-15 1996-10-29 Bio-Virus Research Incorporated Pharmaceutical compositions for the management of premenstrual syndrome and alleviation of menopausal disorders
US5948443A (en) * 1996-02-23 1999-09-07 Medical Doctor's Research Institute, Inc. Acetylsalicylic acid and micronutrient supplementation for nutritional losses and coronary heart disease
US6139872A (en) * 1996-08-14 2000-10-31 Henkel Corporation Method of producing a vitamin product
US6267994B1 (en) * 1996-12-14 2001-07-31 Schaper & Bruemmer Gmbh & Co. Kg Use of extract of cimicifuga racemosa
US20030185905A1 (en) * 1997-05-06 2003-10-02 Roman Conrad Muhlbauer Plant extracts for the treatment of increased bone resorption
US6004558A (en) * 1998-02-25 1999-12-21 Novogen, Inc. Methods for treating cancer with legume plant extracts
US20010036468A1 (en) * 1998-07-25 2001-11-01 Sam-A-Pharmaceuticals Co., Ltd. Soft chewable multivitamin tablet comprising separated active ingredients
US6444218B2 (en) * 1998-07-25 2002-09-03 Sam-A-Pharmaceuticals Co. Ltd. Soft chewable multivitamin tablet comprising separated active ingredients
WO2000018415A1 (en) * 1998-09-30 2000-04-06 Hexal Ag Pharmaceutically active plant preparation for the treatment of migraine
US6200594B1 (en) * 1999-12-29 2001-03-13 Vital Dynamics, Inc. Breast-enhancing, herbal compositions and methods of using same

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110045014A1 (en) * 2006-02-17 2011-02-24 Hideaki Matsuda Acceleration agent of calcium absorption
US9486489B2 (en) 2011-08-19 2016-11-08 Bionorica Se Method for producing dry extracts

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DE10127897A1 (en) 2002-12-19 application
CN100376267C (en) 2008-03-26 grant
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US20040151781A1 (en) 2004-08-05 application
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EP1392337B2 (en) 2009-07-22 grant
JP4945058B2 (en) 2012-06-06 grant
CA2449521A1 (en) 2002-12-19 application
DK1392337T3 (en) 2005-12-27 grant
KR20040011517A (en) 2004-02-05 application
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ES2250674T5 (en) 2009-11-06 grant

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