AU5405299A

AU5405299A - Bone screw

Info

Publication number: AU5405299A
Application number: AU54052/99A
Authority: AU
Inventors: Roger Berger; Piet Reynders
Original assignee: Synthes GmbH
Current assignee: Synthes GmbH
Priority date: 1999-09-08
Filing date: 1999-09-08
Publication date: 2001-04-10
Anticipated expiration: 2019-09-08
Also published as: ATE279887T1; CN1367665A; JP4145044B2; DE59910917D1; CA2405230A1; ES2228085T3; EP1210019B1; JP2003508147A; ES2228085T5; CA2405230C; KR20020035642A; TW466310B; AU757039B2; EP1210019B2; NZ517314A; EP1210019A1; CN1261082C; WO2001017447A1; KR100656573B1

Abstract

The invention relates to a bone screw that is provided with a head (1), a shaft (2), a central longitudinal axis (3), a screw point (4), a surface area (5) an external thread (6) and an entire length (L). A bore (7) that is open in the direction towards the head (1) and extends coaxially in relation to the longitudinal axis (3) is provided. Said bore is connected to the surface area (5) via at least one channel (8) which extends crosswise in relation to the longitudinal axis (3). The bore reaches the outside in the form of at least one perforation (9) through the surface area (5) and is closed in the direction towards the screw point (4). The advantage of the bone screw is that osteocementum can be introduced into the adjacent bone in such a way that an artificial coaxial cement bed for the thread of the bone screw is embodied. The cement bed is only laterally adjacent to the screw such that said screw can be axially screwed further into the forward direction even after the osteocementum has hardened.

Description

WO 01/00046 1 PCT/EPOO/05537 Use of Nanoscale Sterols and Sterol Esters Field of the Invention This invention relates generally to nanoparticles and, more particularly, to the use of nanoscale sterols and sterol esters as food additives. 5 Prior Art Sterols and sterol esters are important raw materials both for cosmetics and pharmaceutical products and for the food industry. For example, it is known that sterols, especially vegetable representatives 10 ("phytosterols"), are incorporated in the basal membrane of the skin and pass to the skin surface through the differentiation of the skin cells. This would explain the caring and protecting effect of phytosterols in skin cosmetics. The topical application of sterols also leads to an increased skin moisture level and to an increased lipid content. This improves the 15 desquamation behavior of the skin and reduces any erythemas present. Overviews on the properties of sterols and sterol esters in cosmetics have been published, for example, by R. Wachter in Parf. Kosm. 75, 755 (1994) and in Cosm. Toil. 110, 72 (1995). Another important property of phytosterols and, above all, of phytosterol esters is their hypo 20 cholesterolemic effect, i.e. their ability after oral ingestion, for example as a margarine additive, significantly to reduce the cholesterol level in the blood which was described as long ago as 1953 by Peterson et al. in J. Nutrit. 50, 1919 (1953). US 3,089,939, US 3,203,862 and DE-OS 20 35 069 (Procter & Gamble) point in the same direction. The active substances are 25 normally added to cooking oils or edible oils and are then taken up through the food. However, the quantities used are generally small and are normally below 0.5% by weight to prevent the edible oils from clouding or WO 01/00046 3 PCT/EPO0/05537 In general, sterols contain 27 to 30 carbon atoms and one double bond in the 5/6 position and occasionally in the 7/8, 8/9 or other positions. Besides these unsaturated species, other sterols are the saturated compounds obtainable by hydrogenation which are known as stanols and which are 5 also encompassed by the present invention. One example of a suitable animal sterol is cholesterol. Typical examples of suitable phytosterols, which are preferred from the applicational point of view, are ergosterols, campesterols, stigmasterols, brassicasterols and, preferably, sitosterols or sitostanols and, more particularly, p-sitosterols or p-sitostanols. Besides 10 the phytosterols mentioned, their esters are preferably used. The acid component of the ester may go back to carboxylic acids corresponding to formula (I): R'CO-OH (I) 15 in which R 1 CO is an aliphatic, linear or branched acyl group containing 2 to 22 carbon atoms and 0 and/or 1, 2 or 3 double bonds. Typical examples are acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, 2-ethyl hexanoic acid, capric acid, lauric acid, isotridecanoic 20 acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, elaidic acid, petroselic acid, linoleic acid, conjugated linoleic acid (CLA), linolenic acid, elaeosteric acid, arachic acid, gadoleic acid, behenic acid and erucic acid and the technical mixtures thereof obtained, for example, in the pressure hydrolysis of natural fats and oils, in 25 the reduction of aldehydes from Roelen's oxosynthesis or as monomer fraction in the dimerization of unsaturated fatty acids. Technical fatty acids containing 12 to 18 carbon atoms, for example cocofatty acid, palm oil fatty acid, palm kernel oil fatty acid or tallow fatty acid, are preferred. It is particularly preferred to use esters of p-sitosterol or p-sitostanol with fatty 30 acids containing 12 to 18 carbon atoms. These esters may be prepared WO 01/00046 5 PCT/EPOO/05537 a surface-active compound dissolved therein, in such a way that the nanoparticles are precipitated by the homogenization of the two immiscible solvents, the organic solvent preferably evaporating. O/w emulsions or o/w microemulsions may be used instead of an aqueous solution. The 5 emulsifiers and protective colloids mentioned at the beginning may be used as the surface-active compounds. Another method for the production of nanoparticles is the so-called GAS process (gas anti-solvent recrystallization). This process uses a highly compressed gas or supercritical fluid (for example carbon dioxide) as non-solvent for the 10 crystallization of dissolved substances. The compressed gas phase is introduced into the primary solution of the starting materials and absorbed therein so that there is an increase in the liquid volume and a reduction in solubility and fine particles are precipitated. The PCA process (precipitation with a compressed fluid anti-solvent) is equally suitable. In 15 this process, the primary solution of the starting materials is introduced into a supercritical fluid which results in the formation of very fine droplets in which diffusion processes take place so that very fine particles are precipitated. In the PGSS process (particles from gas saturated solutions), the starting materials are melted by the introduction of gas under 20 pressure (for example carbon dioxide or propane). Temperature and pressure reach near- or super-critical conditions. The gas phase dissolves in the solid and lowers the melting temperature, the viscosity and the surface tension. On expansion through a nozzle, very fine particles are formed as a result of cooling effects. 25 Commercial Applications The particular fineness of the particles promotes more rapid absorption by the blood serum after oral ingestion by comparison with conventional sterols and sterol esters. Besides the in situ encapsulation of 30 the nanoparticles, the substances may also be dissolved or dispersed in WO 01/00046 7 PCT/EPOO/05537 are shown in Table 1 below. Table I Nanoparticles Ex. Steroll Sol p TI T2 Protective Colloid PSR Sterol Ester v. bar 0 C 0 C nm 1 Phytosterol* C02 200 80 175 Gelatine 60-135 2 Phytosterol* C02 180 70 160 Gelatine 75-125 3 -Sitostanol C02 200 85 180 Gelatine 75-130 4 -Sitostenyl laurate C02 200 85 175 Chitosan 55-140 5 -Sitostanyl stearate C02 200 85 175 Gelatine/chitosan (1:1) 60-150 6 Phytosterol* - - - - Gelatine/chitosan (1:1) 65-150 58.1% by weight p-sitosterol, 29.8% by weight campesterol, 4.5% by weight stigmasterol; 3.8% by weight tocopherol; 0.4% by weight cholesterol; 0.3% by weight squalane; unsaponifiables to 100 Application Examples. Gelatine capsules (weight ca. 1.5 g) containing 5% by weight of p-sitostanol or p-sitostanolester (nanoparticles encapsulated in a gelatine or chitosan matrix and non-nanoscale commercial products) and 0.5% by weight of radioactively marked cholesterol were prepared. To study the hypocholesterolemic effect, male rats (individual weight ca.200 g) were allowed no food overnight. The next day, a size-reduced gelatine capsule was inserted into each test animal via a stomach probe together with a little water containing sodium chloride. After 3, 6, 12, 24 and 48 h, blood was taken from the animals and the content of radioactive cholesterol was determined. The results, which represent the mean value of the measurements of 10 test animals, are set out in Table 2. The figures relating to the reduction in radioactivity are based on a blank group of test animals which were only given gelatine

Claims

1. The use of nanoscale sterols and/or sterol esters with particle diameters of 10 to 300 nm as food additives.

2. The use claimed in claim 1, characterized in that phytosterols or 5 their esters are used.

3. The use claimed in claims 1 and 2, characterized in that sitosterols or their esters are used.

4. The use claimed in at least one of claims 1 to 3, characterized in that nanoscale sterols and/or sterol esters obtained by 10 (a) dissolving the starting materials in a suitable solvent under supercritical or near-critical conditions, (b) expanding the fluid mixture through a nozzle into a vacuum, a gas or a liquid and (c) simultaneously evaporating the solvent 15 are used.

5. The use claimed in at least one of claims 1 to 4, characterized in that nanoparticles surrounded by a toxicologically safe protective colloid are used.

6. The use claimed in claim 5, characterized in that gelatine and/or 20 chitosan is/are used as the protective colloid.

7. The use claimed in at least one of claims 1 to 6, characterized in that the sterols and/or sterol esters are used in quantities of 0.1 to 5% by weight, based on the food.

8. The use claimed in at least one of claims 1 to 7, characterized in that 25 the sterols and/or sterol esters are used in butter, margarine, diet food, frying oils, edible oils, mayonnaises, salad dressings, cocoa products or sausage.

9. The use of nanoscale sterols and/or sterol esters with particle diameters of 10 to 300 nm as active substances for the production of 30 hypocholesterolemic agents.