WO1991016824A1 - Elimination du cholesterol - Google Patents

Elimination du cholesterol Download PDF

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Publication number
WO1991016824A1
WO1991016824A1 PCT/AU1990/000490 AU9000490W WO9116824A1 WO 1991016824 A1 WO1991016824 A1 WO 1991016824A1 AU 9000490 W AU9000490 W AU 9000490W WO 9116824 A1 WO9116824 A1 WO 9116824A1
Authority
WO
WIPO (PCT)
Prior art keywords
cholesterol
adsorbent
emulsion
cyclodextrin
contacted
Prior art date
Application number
PCT/AU1990/000490
Other languages
English (en)
Inventor
David George Oakenfull
Gurcharn Singh Sidhu
Michael Laurence Rooney
Original Assignee
Commonwealth Scientific And Industrial Research Organisation
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
Priority claimed from AU54768/90A external-priority patent/AU633084B2/en
Application filed by Commonwealth Scientific And Industrial Research Organisation filed Critical Commonwealth Scientific And Industrial Research Organisation
Priority to JP90514102A priority Critical patent/JPH05505932A/ja
Publication of WO1991016824A1 publication Critical patent/WO1991016824A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C7/00—Other dairy technology
    • A23C7/04—Removing unwanted substances other than lactose or milk proteins from milk
    • A23C7/043—Removing unwanted substances other than lactose or milk proteins from milk using chemicals in liquid or solid state, e.g. flocculating, adsorbing or extracting agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
    • A23L5/20—Removal of unwanted matter, e.g. deodorisation or detoxification
    • A23L5/27—Removal of unwanted matter, e.g. deodorisation or detoxification by chemical treatment, by adsorption or by absorption
    • A23L5/273—Removal of unwanted matter, e.g. deodorisation or detoxification by chemical treatment, by adsorption or by absorption using adsorption or absorption agents, resins, synthetic polymers, or ion exchangers

Definitions

  • This invention concerns a method for removing cholesterol from organic or biological materials, such as lipid containing foodstuffs of animal origin, and especially from milk and dairy products.
  • This invention is based on the fact that certain steroids or triterpenes and cyclodextrins, have an affinity for cholesterol and bile acids, and we have shown that such agents on binding to selected solid supports form very effective and convenient adsorbents for cholesterol.
  • this invention provides a method for removing cholesterol from organic or biological substances of animal origin wherein such substances are contacted, in emulsion form, with a cholesterol, adsorbent comprising a steroid, a triterpene or a cyclodextrin and/or mixtures thereof chemically bonded to a support.
  • the biological material In instances where the biological material is not in emulsion form it should be dispersed in a suitable liquid to form an emulsion prior to contacting with the adsorbent. However biological materials already in such form, such as milk or cream, may be contacted directly with the adsorbent without any pre- reatment.
  • emulsion as used herein is intended to include miscellar solutions or cholesterol-containing fat associated with protein as in lipoproteins.
  • Typical steroids for use in the practise of this invention include diosgenin, digitonin and tomatidine, and a particularly preferred compound is diosgenin.
  • Suitable triterpenes are medicagenic acid and hederagenin.
  • Cyclodextrins include % , ⁇ - and ⁇ -cyclodextrin, or their modified forms.
  • Silica has proved to be a suitable support material.
  • examples of other materials include, polystyrene, polymethylmethacrylate and cellulose.
  • the adsorbent may itself be the support if it can be presented in the form of relatively insoluble particles. This may be achieved by bonding the adsorbent to itself in such a way as to have active groups on the surface of the particles.
  • the adsorbent may be cross linked to promote insolubility.
  • a further advantageous feature of the aforementioned adsorbents is that they can readily and economically be regenerated for further use by washing with solvents, such as acetic acid, or mixtures of butanol and acetic acid, which remove the cholesterol.
  • solvents such as acetic acid, or mixtures of butanol and acetic acid, which remove the cholesterol.
  • adsorbents used in the method of the invention can work ' quite effectively at lower temperatures even though the conventional method would suggest that higher temperatures should be required to obtain a satisfactory degree and ratio of adsorption.
  • the cholesterol containing fats in many biological materials are solid at low temperature. It is therefore to be expected that the solid fats will reduce the rate of adsorption of cholesterol by the adsorbent in comparison with the liquid form of the fats at higher temperatures. It is believed that the size of cholesterol containing globules of fats in the emulsions is a factor in ensuring that a satisfactory adsorption rate is realised.
  • the fat globules are very small, as in the case of milk, the cholesterol tends to accumulate at the surface of the globules with the result that it can readily transfer to the adsorbent even though the fat globules are solid.
  • the low temperature capability of a preferred method of the invention is particularly useful in relation to biological materials, such as with milk or cream, which spoil if they are not chilled.
  • the temperature at which the absorption is carried out is below 18 C. More preferably a temperature range of 0 to 8 C is appropriate. Where such low adsorption temperatures are used it is preferred that the fats in the emulsion be of sufficiently small size to ensure that at least 30% of the cholesterol is adsorbed within 20 minutes of being contacted with the adsorbent.
  • the average time the biological material will need to be in contact with the adsorbent to achieve an effective degree of adsorption will vary, depending on a number of factors, such as, quantity of adsorbent material and nature of the biological material being treated. However, generally speaking an average contact period of from 1/2 to 20 minutes more preferably 2 to 20 minutes will give satisfactory results.
  • the molar ratio of adsorbent to cholesterol in the biological material should not be lower than 0.5, more preferably it should exceed 50.
  • o Tne ratio may be such as to ensure removal of at least 35% of the cholesterol in the biological material, more preferably 60%.
  • rendering the material to be treated to liquid form eg by dispersion in a solvent or emulsion, 0 ⁇ ) bringing the liquid material into intimate contact with the adsorbent, eg by flow through a column packed with the adsorbent, or by agitation with the adsorbent, iii) separating the cholesterol-reduced material from c the adsorbent, iv) regenerating the adsorbent by elution of the adsorbed cholesterol.
  • the invention also covers biological materials which have been reduced in cholesterol in accordance with the method of the - 05 invention.
  • Cholesterol labelled with 14C was emulsified by using a sonicator with oleic acid, nomo-olein and taurocholic acid in phosphate buffer (pH7.0). This emulsion was shaken with (25R)-spirost-5en-38-ol (C ⁇ H ⁇ -O.,) bonded to silica gel. The adsorbent removed 82% of the cholesterol from the emulsion. (As shown in Table 2.) Ordinary, untreated silica had no significant effect on the . cholesterol content of the emulsion.
  • the emulsions were prepared in isotonic phosphate buffer and contained 14C-labelled Cr-EDTA added to provide a means of monitoring any uptake of water by the adsorbent. Two emulsions were used:
  • a variety of solid adsorbents can be prepared.
  • the choice of chemistry for the attachment procedure will depend on the nature of the solid support.
  • Adsorption of cholesterol was determined by shaking 4 ml of milk or emulsion with (typically) 0.1 g of the solid adsorbent.
  • ⁇ -cyclodextrin Silicic acid (10 g) and glycidoxypropyltrimethoxysilane (30 g) were made into a slurry with dry dimethyl formamide (600 ml). Dry ⁇ -cyclodextrin (30 g) was dissolved in dry dimethyl formamide (375 ml) and sodium hydride (9 g) added with stirring, allowed to react for 15 min. and the solution filtered, taking precautions to exclude water. The slurry and the solution were mixed and then refluxed under dry conditions for 4 hours. The solid product was collected by filtration and washed with dimethyl formamide, methanol and water. The product was finally dried with gentle heat under vacuum. The effectiveness of the product is shown in Table 3.
  • 0.1 adsorbent with 4 ml emulsion - coars silica particle size 70-230 ⁇ diameter - fine silica has a surface area of 200 ⁇ 30 ⁇ per gram, lg adsorbent wites 10ml milk.
  • Diosgenin the procedure for attachment was the same as that described for cyclodextrin. Butterfat containing
  • Polymethylmethacrylate ⁇ -cyclodextrin Polymethylmethacrylate (4. 1 g) was dissolved in pyridine (100 ml ) and _ _
  • ⁇ -cyclodextrin (3.25 g) was added and dissolved. To this was added 1 ml of a methanolic solution of sodium methoxide (200 g/1) and the mixture refluxed for 30 min. The solid product that formed was filtered, washed with water and dried under vacuum.
  • Tomatine (1 g) was dissolved in dry dimethyl formamide (5 ml) and sodium hydride (0.5 g) added. The reaction was allowed to proceed for 10 min. Epichlorohydrin (20 ml) was then added and the solution heated at 120 for 4 hour. The excess epichlorohydrin was removed by distillation. The solid precipitate thus obtained was washed with dimethyl formamide and ethanol and dried under vacuum.
  • ⁇ -cyclodextrin ⁇ -cyclodextrin (5 g) was wetted with water ( 2ml) and dissolved in 50% aqueous sodium hydroxide (6ml). Epichlorohydrin (50ml) was added and allowed to react at room temperature (ca 20 ) for 12hr. The solid product was washed with methanol, hot water and cold water.
  • adsorbents according to this invention might form the basis of pharmaceutical products or dietary supplements for reducing intestinal absorption of cholesterol or bile acids.
  • the adsorbents of this invention might be used to extract cholesterol and bile acids from source material, such as bile (an abattoir waste).
  • source material such as bile (an abattoir waste).
  • the adsorbed cholesterol or bile acids could then be selectively released by washing with suitable solvents, and used as precursors for the synthesis of steroid-based drugs.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nutrition Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Fats And Perfumes (AREA)
  • Dairy Products (AREA)
  • Steroid Compounds (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

On élimine le cholestérol de substances organiques ou biologiques telles que le lait et les produits laitiers. On procède à ladite élimination en mettant la substance en contact avec de la cyclodextrine ayant été liée à un support inerte. Afin de réduire le risque de détérioration, la température doit rester inférieure à 18 °C pendant l'élimination du cholestérol. On régénère la cyclodextrine par élution du cholestérol adsorbé à l'aide d'acide acétique ou de mélanges de butanol et d'acide acétique utilisés comme éluants.
PCT/AU1990/000490 1990-05-08 1990-10-12 Elimination du cholesterol WO1991016824A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP90514102A JPH05505932A (ja) 1990-05-08 1990-10-12 コレステロール除去

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU54768/90A AU633084B2 (en) 1989-05-10 1990-05-08 Cholesterol removal
AU54768/90 1990-05-08

Publications (1)

Publication Number Publication Date
WO1991016824A1 true WO1991016824A1 (fr) 1991-11-14

Family

ID=3740645

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU1990/000490 WO1991016824A1 (fr) 1990-05-08 1990-10-12 Elimination du cholesterol

Country Status (4)

Country Link
EP (1) EP0527735A4 (fr)
JP (1) JPH05505932A (fr)
CA (1) CA2082388A1 (fr)
WO (1) WO1991016824A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995004473A1 (fr) * 1993-08-04 1995-02-16 Yissum Research Development Company Of The Hebrew University Of Jerusalem Procede destine a enlever du cholesterol de produits alimentaires
US5449771A (en) * 1993-03-31 1995-09-12 Nihon Shokuhin Kako Co., Ltd. Method for recovering cyclodextrin
WO1999017620A1 (fr) * 1997-10-06 1999-04-15 Eugene Science Inc. Procede de reduction de la teneur en cholesterol dans les produits laitiers
US6110517A (en) * 1997-08-02 2000-08-29 Se Jong University Method for removing cholesterol from milk and cream
CN104397828A (zh) * 2014-11-19 2015-03-11 渤海大学 一种改性玉米醇溶蛋白复合缓释抗菌液态膜的制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100791978B1 (ko) * 2005-06-21 2008-01-04 곽해수 콜레스테롤 제거용 베타-싸이클로덱스트린의 가교화 및그의 재생방법

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2844989A (en) * 1988-01-22 1989-07-27 Asterol International Process for the elimination of steroid compounds contained in a substance of biological origin
US4880573A (en) * 1986-07-24 1989-11-14 Monserbio Process for eliminating cholesterol contained in a fatty substance of animal origin and the fatty substance with reduced cholesterol obtained

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3450541A (en) * 1966-06-29 1969-06-17 Us Agriculture Rapid quantitative removal of natural sterols from lipids
JPS58116415A (ja) * 1981-12-28 1983-07-11 Riyoushiyoku Kenkyukai コレステロ−ル低下剤の使用方法
US7549988B2 (en) * 2004-08-30 2009-06-23 Boston Scientific Scimed, Inc. Hybrid lesion formation apparatus, systems and methods

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4880573A (en) * 1986-07-24 1989-11-14 Monserbio Process for eliminating cholesterol contained in a fatty substance of animal origin and the fatty substance with reduced cholesterol obtained
AU2844989A (en) * 1988-01-22 1989-07-27 Asterol International Process for the elimination of steroid compounds contained in a substance of biological origin

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
PATENTS ABSTRACTS OF JAPAN, C-188, page 75, JP,A, 58-116415 (RIYOUSHIYOKU KENKIYUUKAI) 11 July 1983 (11.07.83). *
PATENTS ABSTRACTS OF JAPAN, C-277, page 128, JP,A,59-224668 (HAYASHIBARA SEIBUTSU KAGAKU KENKYUSHO K.K.) 17 December 1984 (17.12.84). *
See also references of EP0527735A4 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5449771A (en) * 1993-03-31 1995-09-12 Nihon Shokuhin Kako Co., Ltd. Method for recovering cyclodextrin
KR100319784B1 (ko) * 1993-03-31 2002-07-04 히라타노부오 시클로덱스트린의회수방법
WO1995004473A1 (fr) * 1993-08-04 1995-02-16 Yissum Research Development Company Of The Hebrew University Of Jerusalem Procede destine a enlever du cholesterol de produits alimentaires
US6110517A (en) * 1997-08-02 2000-08-29 Se Jong University Method for removing cholesterol from milk and cream
WO1999017620A1 (fr) * 1997-10-06 1999-04-15 Eugene Science Inc. Procede de reduction de la teneur en cholesterol dans les produits laitiers
CN104397828A (zh) * 2014-11-19 2015-03-11 渤海大学 一种改性玉米醇溶蛋白复合缓释抗菌液态膜的制备方法

Also Published As

Publication number Publication date
JPH05505932A (ja) 1993-09-02
EP0527735A1 (fr) 1993-02-24
CA2082388A1 (fr) 1991-11-09
EP0527735A4 (en) 1993-09-15

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