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WO1997031021A1 - Preparation de calcitonine orale et procede de recuperation de la calcitonine a partir de coquilles d'oeufs - Google Patents

Preparation de calcitonine orale et procede de recuperation de la calcitonine a partir de coquilles d'oeufs Download PDF

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Publication number
WO1997031021A1
WO1997031021A1 PCT/NL1997/000072 NL9700072W WO9731021A1 WO 1997031021 A1 WO1997031021 A1 WO 1997031021A1 NL 9700072 W NL9700072 W NL 9700072W WO 9731021 A1 WO9731021 A1 WO 9731021A1
Authority
WO
WIPO (PCT)
Prior art keywords
calcitonin
eggshells
product
preparation
oral
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.)
Ceased
Application number
PCT/NL1997/000072
Other languages
English (en)
Inventor
Anne Schaafsma
Cornelis Glas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FrieslandCampina Nederland BV
Original Assignee
Friesland Brands BV
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Friesland Brands BV filed Critical Friesland Brands BV
Priority to AU17361/97A priority Critical patent/AU1736197A/en
Publication of WO1997031021A1 publication Critical patent/WO1997031021A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/585—Calcitonins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention relates to an oral preparation comprising calcitonin or a product having calcitonin-like activity, and to a method for obtaining calcitonin or a product having calcitonin-like activity and products containing calcitonin or said product having calcitonin-like activity.
  • Calcitonin is a polypeptide hormone which contains 32 amino acids. In mammals it is produced in the parafollicular cells of the thyroid gland (thyrocalcitonin) ; and in birds and fish in the ultimobranchial body. Calcitonin is used therapeutically, inter alia in the treatment of Page ' s disease, in hypercalcemia and (post-menopausal) osteoporosis. It inhibits the action of osteoclasts and promotes the clearance of calcium and phosphate via the urine. In addition, it has been reported that calcitonin reduces pain phenomena associated with these disorders .
  • calcitonin is particularly recovered in pure and highly active form from the ultimobranchial glands of salmon, eel or fowl.
  • calcitonin is recovered from salmon through specific binding to columns and subsequent purification.
  • the calcitonin thus recovered is 40 times more active than calcitonin of human origin.
  • Calcitonin is employed both in natural and in modified form.
  • European patent application 0 261 552 describes the production of calcitonin through recombinant DNA techniques.
  • the simplest and for patients least interfering route for administering a pharmaceutically active agent is via the gastrointestinal tract, with the pharmaceutical being ingested orally.
  • this application route is not always so efficient for polypeptides such as calcitonin.
  • Intestinal enzymes mainly proteases, lead to the decomposition of the polypeptide into smaller peptides and amino acids, which decomposition products are inactive.
  • calcitonin preparations which may or may not be derivatized or modified, have hitherto been chiefly administered parenterally, through inhalation, injection, or vaginal or rectal application.
  • Japanese publication 93-274737 describes special calcitonin derivatives having an improved enteric absorption.
  • fatty acid groups or lower alkoxy- carbonyl groups are coupled to the polypeptide chain.
  • the derivatives are suitable for the treatment of pain resulting from osteoporosis and hypercalcemia, and improve the growing-on of bone mass.
  • European patent application 0 535 827 proposes the incorporation of calcitonin into fatty (emulsifier) material and the encapsulation of calcitonin in gelatin. These calcitonin products are better absorbed without necessitating an absorption promoter.
  • Japanese publication 62-010020 describes a composition which, in addition to calcitonin, contains a fatty ester with an HLB of 11-16. This composition is claimed to have an improved absorption behaviour.
  • international patent application 87/00750 describes a method for the same purpose, in which calcitonin is enveloped in a thin phospholipid skin, whereby it is brought into a liposome form.
  • the invention relates to calcitonin originating from eggshells.
  • the invention relates to a method for obtaining an orally applicable calcitonin product, in which calcitonin is released from eggshells.
  • calcitonin can be taken up into an aqueous medium or an aqueous solvent system, but also in other solvents in which calcitonin dissolves, in contrast with the inorganic eggshell matrix.
  • calcitonin can be obtained by dissolving the eggshell matrix at least partly.
  • Eggshells with or without membrane residues, constitute an amply available waste product.
  • the eggshells are first ground, preferably to form an eggshell flour as fine as possible. For this purpose, it is not necessary to separate the membrane residues from the eggshells.
  • the eggshells before being ground, can be dried, which facilitates the grinding treatment.
  • the starting product can be priorly sterilized without the activity of the calcitonin diminishing unacceptably.
  • the calcitonin is sufficiently protected by the lime matrix of the eggshell .
  • a major advantage of the method according to the invention is that no extensive steps for purifying the calcitonin product are necessary. It is no problem, indeed an advantage, if not all residues of the eggshell matrix are removed. By administering calcitonin in combination with a calcium product, the effect of calcitonin is considerably enhanced.
  • calcitonin can be administered by administering eggshells, in whatever form, orally.
  • Eggshells contain calcitonin in a form and amount such that its decomposition in the gastrointestinal tract can be avoided or inhibited to a sufficient extent, and that the calcitonin can be absorbed into the system and can work the desired effect there.
  • the calcitonin products according to the invention give a physiological pain-reducing effect upon oral administration. Moreover, these products can be employed in all mammals suffering from a disorder that can be treated with calcitonin. Further, the calcitonin product according to the invention can be used prophylactically.
  • the invention further relates to an oral preparation containing calcitonin obtained from eggshells.
  • a magnesium source is present as well.
  • This magnesium contributes to the pain reducing action of the calcitonin.
  • the ratio of calcium to magnesium in the preparation according to the invention is between 3:1 and 12:1. Both the calcium and the magnesium can originate from eggshells and/or from external sources . This ratio is so chosen for physiological reasons, namely, to effect an optimum calcium retention in bones. It is noted that in Magnesium Res. 2 (1989) 142 it is described that magnesium upon administration to osteoporosis patients has a pain relieving effect.
  • the preparations according to the invention with components which are known to positively influence calcium retention, in particular with vitamin D or with a source rich in vitamin D.
  • vitamins A, K and/or C sources of fluoride ions, vanadium ions, boron ions and/or silicon ions, glycine, and casein phosphopeptides.
  • the oral preparation according to the invention can be used in any known orally applicable form.
  • the preparation is in the form of a pill, a tablet to be swallowed or chewed, or a liquid preparation. In this last case, by choosing a suitable liquid medium in the method according to the invention, the product directly obtained can be administered.
  • the calcitonin obtained from eggshells can be incorporated in a food or be used as a food supplement, for instance for prophylactic reasons.
  • the invention further relates to a method for administering calcitonin, in which an eggshell product is administered orally.
  • the invention relates to the use of eggshells as a calcitonin source.
  • the invention is presently explained in and by the following, non-limiting examples.
  • PCT/NL/95/00396 contained approximately 38% by weight of calcium, 0.4% by weight of magnesium, 0.1% by weight of phosphorus and 0.6% by weight of nitrogen. This product was suspended in an amount of 10% in 90 ml water, followed by a test for calcitonin. In the suspension the calcitonin content was determined according to the standard method of Nicholson (Nicholson Institute) .
  • the suspension contained 0.09 ⁇ g calcitonin.
  • capsules for oral use containing 0.7 g fine calcitonin-containing eggshell flour and 0.05 g of a mixture containing sodium ascorbate, zinc lactate, vitamins E, D3 , B6, K, B2, Bl, B12, silicon dioxide, boric acid and milk protein (casein, whey protein) .
  • Example 2 The product according to Example 2 was prepared, but 0.7 g calcitonin-containing eggshell flour was replaced with 0.5 g calcitonin-containing eggshell flour and 0.2 g magnesium hydroxycarbonate.
  • a powdery product was prepared by mixing milk powder having a reduced fat content with a mixture of eggshell flour and maltodextrin, jointly dried on a wheel drier, as well as a vitamin-mineral premix.
  • the product contained 21 g milk protein, 14 g fat, 2.2 g calcium, of which 1.5 g originating from fine eggshell flour, and 0.6 g magnesium.
  • Added as microingredients by way of the vitamin-mineral premix were iron, zinc, copper, iodide, vitamins A, C, D, E, K, Bl, B2, B6, B12, folic acid, niacin, panthothenic acid, biotin.
  • the Ca/Mg ratio was ⁇ 4:1.
  • Example 5 The product according to Example 4 was prepared, but the milk powder of reduced fat content was replaced with a mixture of cereal flour and soybean.
  • Example 6 The product according to Example 4 was given for a period of 4 months to experimental subjects with proven osteoporosis, who had pain complaints which had hitherto been fought with current pain killers.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne la calcitonine que l'on peut obtenir à partir de coquilles d'oeufs. En outre, elle se rapporte à un procédé d'obtention d'un produit à base de calcitonine, destiné à une administration orale, et dans lequel la calcitonine est libérée à partir des coquilles d'oeufs, ainsi qu'à une préparation orale contenant la calcitonine obtenue à partir des coquilles d'oeufs. Enfin, l'invention concerne un procédé d'administration de la calcitonine, dans lequel le produit à base de coquilles d'oeufs est administré oralement, de même que l'utilisation de coquilles d'oeufs en tant que source de calcitonine.
PCT/NL1997/000072 1996-02-20 1997-02-19 Preparation de calcitonine orale et procede de recuperation de la calcitonine a partir de coquilles d'oeufs Ceased WO1997031021A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU17361/97A AU1736197A (en) 1996-02-20 1997-02-19 Oral calcitonin preparation and method for recovering calcitonin from eggshells

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL1002400 1996-02-20
NL1002400A NL1002400C2 (nl) 1996-02-20 1996-02-20 Oraal calcitonine-preparaat en werkwijze voor het winnen van calcitonine.

Publications (1)

Publication Number Publication Date
WO1997031021A1 true WO1997031021A1 (fr) 1997-08-28

Family

ID=19762353

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL1997/000072 Ceased WO1997031021A1 (fr) 1996-02-20 1997-02-19 Preparation de calcitonine orale et procede de recuperation de la calcitonine a partir de coquilles d'oeufs

Country Status (4)

Country Link
AU (1) AU1736197A (fr)
NL (1) NL1002400C2 (fr)
WO (1) WO1997031021A1 (fr)
ZA (1) ZA971382B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999026641A1 (fr) * 1997-11-21 1999-06-03 Ruepp Michel O Utilisation de putamen ovi
WO2001074491A3 (fr) * 2000-04-03 2002-02-21 Joseph Herman Macneil Procede et dispositif de traitement de coquilles d'oeuf de recuperation

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0146842A1 (fr) * 1983-12-08 1985-07-03 Mitsubishi Petrochemical Co., Ltd. Calcitonine et son isolement
EP0347899A2 (fr) * 1988-06-24 1989-12-27 BIOMIN, akciová spolocnost' Compositions pharmaceutiques à base de coquille d'oeuf et leur préparation et utilisation
WO1996000578A1 (fr) * 1994-06-28 1996-01-11 Aar Pharma Adler Apotheke Preparation a base de coquilles d'oeufs dite 'putamen ovi'
WO1996015678A1 (fr) * 1994-11-23 1996-05-30 Friesland Brands B.V. Produit a base de lait enrichi de coquille d'×uf broyee

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0146842A1 (fr) * 1983-12-08 1985-07-03 Mitsubishi Petrochemical Co., Ltd. Calcitonine et son isolement
EP0347899A2 (fr) * 1988-06-24 1989-12-27 BIOMIN, akciová spolocnost' Compositions pharmaceutiques à base de coquille d'oeuf et leur préparation et utilisation
WO1996000578A1 (fr) * 1994-06-28 1996-01-11 Aar Pharma Adler Apotheke Preparation a base de coquilles d'oeufs dite 'putamen ovi'
WO1996015678A1 (fr) * 1994-11-23 1996-05-30 Friesland Brands B.V. Produit a base de lait enrichi de coquille d'×uf broyee

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999026641A1 (fr) * 1997-11-21 1999-06-03 Ruepp Michel O Utilisation de putamen ovi
DE19751681A1 (de) * 1997-11-21 1999-07-29 Michael O Ruepp Aar Pharma Verwendung von Putamen ovi
WO2001074491A3 (fr) * 2000-04-03 2002-02-21 Joseph Herman Macneil Procede et dispositif de traitement de coquilles d'oeuf de recuperation
US6899294B2 (en) 2000-04-03 2005-05-31 The Penn State Research Foundation Hatchery eggshell waste processing method and device

Also Published As

Publication number Publication date
NL1002400C2 (nl) 1997-08-21
AU1736197A (en) 1997-09-10
ZA971382B (en) 1997-09-09

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