WO1995012391A1 - Poudres a base de gelatine a caracteristiques de couleur, d'odeur et de mise en ×uvre sous forme de comprimes ameliorees - Google Patents

Poudres a base de gelatine a caracteristiques de couleur, d'odeur et de mise en ×uvre sous forme de comprimes ameliorees Download PDF

Info

Publication number
WO1995012391A1
WO1995012391A1 PCT/EP1994/003570 EP9403570W WO9512391A1 WO 1995012391 A1 WO1995012391 A1 WO 1995012391A1 EP 9403570 W EP9403570 W EP 9403570W WO 9512391 A1 WO9512391 A1 WO 9512391A1
Authority
WO
WIPO (PCT)
Prior art keywords
gelatin
powder
molecular weight
color
vitamin
Prior art date
Application number
PCT/EP1994/003570
Other languages
English (en)
Inventor
Rudolph E. Lisa
Thomas B. Soblesky
Anthony M. Lepore
Gerald A. Fritz
Original Assignee
Basf Corporation
Basf Aktiengesellschaft
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 Basf Corporation, Basf Aktiengesellschaft filed Critical Basf Corporation
Publication of WO1995012391A1 publication Critical patent/WO1995012391A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1658—Proteins, e.g. albumin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2063—Proteins, e.g. gelatin

Definitions

  • Gelatin Powders with Improved Tabletability Color and Odor Characteristics
  • the invention relates to free-flowing gelatin powders, and more specifically to those powders comprising partially hydrolyzed gelatin and one or more edible oils having improved tabletability, color and odor characteristics.
  • Gelatin is a mixture of proteins obtained through hydrolysis of collagen after boiling the skin, ligaments, tendons, etc. of an animal, typically farm mammals such as ruminants and swine.
  • the gelatin is hydrolyzed by one or more processes, for example by acid or base or enzyme hydrolysis, and then an emulsion is prepared with the edible oil(s).
  • the resulting emulsion is then spray dried to produce a powder.
  • the powder can then be incorporated into animal feeds for both domestic pets and commercial livestock.
  • the dried powder consisting of gelatin encapsulated oil can also be utilized in vitamin and pharmaceutical preparations for human consumption, for example by compressing the powder mixed with appropriate excipients into tablets.
  • gelatin can be partially hydrolyzed so that it will have a molecular weight within the range of 15,000 to 35,000 in the final gelatin powder.
  • an emulsion prepared from this hydrolyzed gelatin and Vitamin E can then be spray dried into powder and pressed into tablets having a hardness in excess of 20 or even 25 S.C.U. 's.
  • Finnan's partial hydrolysis step is capable of employing any commercially prepared gelatin with a molecular weight in excess of 35,000.
  • any gelatin with a low Bloom value between 30 and 100g could be used in partial hydrolysis so long as the final gelatin powder had a molecular weight within the range set forth by Finnan.
  • a gelatin with an acceptable Bloom strength whose initial weight average molecular weight (Mw) was listed as about 40,000 appeared to be as efficacious in Finnan' s process as a gelatin with an initial molecular weight as high as 90,000. Since all these gelatins, either separately or in blends, would ultimately be partially hydrolyzed down to a molecular weight within the range of 15,000 to 35,000, it would not matter what the initial molecular weight was .
  • Molecular weight dispersity is a measure of Mw (weight average molecular weight)/Mn (number average molecular weight).
  • the dispersity of a molecular weight distribution is also a measure of the broadness of the distribution - a high dispersity has relatively more large and small molecules mixed together.
  • a mono- molecular weight distribution (the idealized case where every molecule has the same molecular weight) would appear as a "spike" on a graph with a dispersity value of one.
  • a low molecular weight dispersity gelatin imparts certain technical and commercial advantages to the final gelatin product, as compared with a higher molecular weight dispersity gelatin. This is because initial molecular weight dispersity appears to have a substantial effect on the final odor, compressibility and color of the partially hydrolyzed gelatin powder product.
  • gelatin powders prepared from gelatins with higher initial molecular weight dispersities seem to have higher amine contents in the form of a greater number of low molecular weight molecules which can volatilize, imparting odor. Higher amine content translates into higher odor, while the converse is true for those gelatin powders whose amine content is relatively lower.
  • a free-f lowing, gelatin-based powder having improved tabletability, color and odor characteristics, and comprising partially hydrolyzed gelatin having a molecular weight within the range of about 15,000 to about 35,000, with the gelatin prior to hydrolysis having a molecular weight dispersity of not greater than about 7.0.
  • the gelatin-based powder has at least one edible oil selected from the group consisting of fat-soluble vitamins and flavor oils, and especially vitamin E oil.
  • vegetable oil selected from the group consisting of fat-soluble vitamins and flavor oils, and especially vitamin E oil.
  • gelatin-based refers simply to gelatin in combination with one or more additional ingredients.
  • a free-f lowing, gelatin-based vitamin powder which has low odor bodies (amines as measured in p.p.m.'s of ammonia) or is substantially odorless, has a whiteness or L* value (hereinafter defined) of at least about 95.0, and a compressibility factor of at least about 15 average S.C.U.'s.
  • Compressibility factor refers to the ability of the powder to be formed into tablets by methods known in the art such that the tablets so formed will have the stated hardness values in S.C.U.'s.
  • Figure 1 is a graph of molecular weight distribution or dispersity from gel chromatography for a sample of gelatin.
  • Figure 2 is a three-dimensional colorimeter scale.
  • the product according to the various embodiments of the invention is a free-flowing, gelatin-based nutritional powder having partially hydrolyzed gelatin and one or more edible oils.
  • the edible oil may be any oil which has nutritional characteristics.
  • Preferred edible oils are fat-soluble vitamins and flavor oils. Especially preferred fat-soluble vitamins include A, D and E, with E being particularly preferred.
  • Vitamin E is alphatocopherol.
  • Vitamin E acetate is alphatocopherol acetate.
  • the final product will contain about 20 to about 70% by weight of one or more fat-soluble vitamin oils and flavor oils, more desirably about 40 to 60%, and especially about 45 to about 55% by weight. (Unless otherwise specified, all percentages set forth herein are based on weight of the total composition.)
  • Gelatin will comprise substantially the reminder of the composition in amounts of from about 80 to about 30%, more preferably from about 60 to about 40%, and especially about 55 to about 45% by weight.
  • composition of the invention may contain small amounts of excipients, binders, and stabilizers, hereinafter described, in total amounts of from about 0.1 to about 3% of the composition.
  • the gelatin for use in the partially hydrolyzed gelatin product of the invention will have an initial molecular weight dispersity of less than about 7.0, more preferably less than about 6.6 or even about 6.5. It is especially desirable that the initial molecular weight dispersity of the gelatin to be hydrolyzed not be more than about 6.0, and values as low as about 5.5 or even less are within the scope of the invention. In principle, the lower the initial molecular weight dispersity, the better.
  • Gelatins are in general, hydrolyzed by three different kinds of reagents: acids, bases, and enzymes. Although acids, bases, and enzymes each produce somewhat different hydrolyzed gelatins, it is possible to produce a gelatin of any desired Bloom strength (an arbitrary scale for rating the strength of certain gels from 0 to 300) via either acid or base or enzyme hydrolysis.
  • Gelatins produced by acid processing are generally referred to as Type A gelatins, while the gelatin produced by base processing are referred to as Type B gelatins.
  • Gelatin production is carried out by the hydrolysis of collagen.
  • Type B gelatins are produced by subjecting, for example, bone to the action of a strong base, followed by rinsing the base off, followed by "cooking" the treated bone in boiling water to extract gelatin.
  • Type B gelatin is a preferred starting material for use in the composition of the invention. Particularly preferred is Type B calfskin gelatin available as "SPA" from Croda Ltd. of Cheshire, United Kingdom. This gelatin has an initial molecular weight within the range of about 40,000 to -about 45,000, with 42,500 being about average. The Bloom strength is listed as being 65. Gelatins with Blooms within the range of about 30 to about 100 g are useful in the invention, with those in the range of about 60 to about 90 g being preferred, and about 65 to about 75 being more preferred.
  • the gelatin will be partially hydrolyzed so that it will have a final weight average molecular weight that is within the range of about 15,000 to about 35,000, preferably within the range of about 20,000 to about 32,000, more preferably about 24,000 to about 32,000, as determined by gel permeation chromatography or GPC.
  • the partial hydrolysis of the starting gelatin may be carried out by either acid hydrolysis, base hydrolysis, or enzyme hydrolysis.
  • partial hydrolysis refers to that hydrolysis which is terminated prior to full hydrolysis of the initial starting gela tin. Enzymatic hydrolysis is preferred over either acid or base hydrolysis.
  • the enzyme to be used in the enzyme hydrolysis is one or more proteolytic enzymes.
  • the proteolytic enzyme is an endopeptidase. It is also preferred that the proteolytic enzyme used is a member selected from the group consisting of proteases from B. subtilis strains and neutral fungal proteases from
  • Aspergillus cultures It is most preferred that the enzyme is subtilis.
  • the hydrolysis is controlled by any one or more of several methods of deactivating the enzyme.
  • Specific methods for enzyme deactivation comprise: (1) addition of acid to lower the pH enough to render the enzyme inactive; (2) the addition of an effective chelating agent in an amount sufficient to deactivate the enzyme; (3) heating the enzyme enough to cause deactivation; (4) carrying out the partial hydrolysis at a substantially constant temperature whereby the enzyme is deactivated, by the effect of the temperature, by the time the enzyme produces a desired degree of partial hydrolysis of the gelatin.
  • (3) and (4) may be particularly preferred by those skilled in the art.
  • a substantially constant temperature within the range of about 400 to about 950 C, with about 570 C being preferred.
  • an emulsion is prepared using one or more edible oils, such as flavor oils or fat-soluble vitamins.
  • edible oils such as flavor oils or fat-soluble vitamins.
  • vitamin E oil is preferred.
  • the emulsion is comprised of oil droplets within an aqueous gelatin solution.
  • substantially complete emulsion refers to an emulsion having substantially 100 percent of the oil in the emulsified or droplet form.
  • substantially stable emulsion refers to an emulsion which will show zero visible, or at most negligible demulsification, after standing for a period of about three hours.
  • the emulsion is then spray dried, and the product so produced is a free-f lowing edible powder.
  • spray drying refers to the emulsion from the fluid state into a dried particulate form by spraying the emulsion into a hot drying medium such as a chamber using apparatus known in the art, such as one or more spray nozzles.
  • the resulting product is a powder which may exhibit a very small degree of granulation or agglomeration.
  • the final spray dried product may be utilized as is, but preferably has added thereto one or more stabilizers to inhibit the microbial growth in the emulsified product.
  • the stabilizer is at least one compound obtained from the group consisting of sodium benzoate, potassium sorbate, esters of p-hydroxybenzoic acid, and propionic acid.
  • the stabilizer may be present in the final powder composition in amounts of from about 0.1 to about 0.5 by weight.
  • the final powder in some embodiments may also have silica present in amounts of from about 0.5 to about 2% by weight. In more preferred embodiments, the silica will be present in an amount of about 1% by weight.
  • the silica is introduced into the spray chamber used for drying the gelatin-oil emulsion via a separate nozzle. The silica coats the droplets and prevents them from adhering to the walls of the chamber as well as keeping the droplets from adhering to one another.
  • Preferred for use as part of the invention is AEROSIL ® 200 silica available from Degussa
  • the final free-flowing gelatin-based powder may be, if desired, compressed into one or more tablets .
  • the various apparatus and methods for compressing tablets is known in the art, and may be utilized to form tablets of any desired shape or size.
  • Tablet formation may be accomplished by using a hydraulic or mechanically operated press with platens containing a mold having a plunger and a die. The material flows into the die where the plunger compresses it, then ejects it in the form of a tablet.
  • a hydraulic or mechanically operated press with platens containing a mold having a plunger and a die. The material flows into the die where the plunger compresses it, then ejects it in the form of a tablet.
  • Various excipients such as binders, glidants (or flow aids), disintegrants, and fillers heretofore described, as well as those known to the skilled artisan, are often used to aid in formation of suitable tablets.
  • a number of quantitative tests are conducted on the formed tablets to determine suitability. One such test is for tablet hardness.
  • the tablet is subjected to a force until breakage and the magnitude of this force at breakage is measure.
  • Those skilled in the art are familiar with such equipment, for example, the Schleuniger-2E harness tester. Such devices measure the harness at breakage in Strong Cobb Units (or "S.C.U.'s").
  • Tablets prepared from the free-flowing powder according to the various embodiments of the invention should have an average hardness value of at least about 15 S.C.U.'s and more desirably about 18 S.C.U.'s or greater.
  • an average hardness value of at least about 15 S.C.U.'s and more desirably about 18 S.C.U.'s or greater.
  • enough of the gelatin- based vitamin E powder is processed to make about 1000 tablets, or a batch. Each tablet weighs about 435 mg. +/- 2 mg.
  • 10 tablets are randomly selected and their strengths measured. The hardness of these 10 tablets is then averaged to obtain average hardness value.
  • batch size, tablet weight, and number of tablets used to determine the average hardness value may vary.
  • tablets have an S.C.U. value of at least about 20 or even about 22. It is also within the scope of the invention that tablets be as hard as about 24 S.C.U.'s or even greater. It is possible, for example, to obtain tablets with S.C.U. values of as great as about 28 S.C.U.'s.
  • the "compressibility factor" of the free-flowing gelatin powder according to the invention will be such that tablets prepared from the powder consistent with tabletting methods known in the art will have hardness values such as those set forth above.
  • the final gelatin powder of the invention will also have a whiteness or "L*" factor of at least about 95.0, more preferably at least about 95.3.
  • An L* factor of about 95.5 is even more desirable, and L* values as high as 95.8 and higher are within the scope of the invention.
  • L* is a measure of the whiteness of the gelatin powder on a scale of 0 (black) to 100 (white).
  • the a* and b* coordinates represent color variations.
  • An absolute white sample will therefore have an L* value of 100 and a* and b* values both equal to 0.
  • Figure 2 provides the complex mathematical formulae for determining L* values. This job, however, is handled by a device known as a colorimeter.
  • a SP-68 colorimeter made by X-Rite of Grand Rapids, MI is preferred.
  • the scale shown in Figure 2 was obtained from Hunterlab of Reston, Virginia.
  • the final gelatin powder of the invention will be low in odor (having reduced odor bodies), or be substantially odorless, that is, have no discernible smell via the human nose.
  • a high molecular weight dispersity gelatin seems to have a high amount of low molecular weight amines by virtue of the broader distribution of the size of the molecules, that is, relatively more low molecular weight material.
  • a narrow dispersity gelatin material seems to have relatively less of the small molecular weight amines which constitute the odor bodies.
  • the hydrolyzed gelatin powder of the invention will have less than about 500 ppm (parts per million), and preferably less than about 400 ppm of amine content. It is also within the scope of the invention that the amine content be under about 200 ppm of amine. It is especially desirable that the gelatin powder after hydrolysis have less than about 150 ppm of amine.
  • Amine content can be determined analytically. Briefly stated, dissolved gaseous amines in a sample solution diffuse through the gas membrane of an ammonia electrode until the partial pressure on both sides of the membrane is the same. The partial pressure of dissolved amines is related to their concentration using
  • Vitamin E Free Flowing Powder A vessel was charged with 1720 lbs. of water and heated via a hot water jacket to 135o F. 6 lbs. of sodium benzoate, 3 lbs. of potassium sorbate and 1400 lbs. of Croda SPA gelatin were charged to the vessel and dissolved using a homogenizer. To this was added 20 ml. of Proteolytic L 175 enzyme (from Solvay Enzymes, Inc. of Elkhar, Indiana) dispersed in 2 lbs. of water. The batch was mixed at 135°F for 20 minutes. Then 1542 lbs. of vitamin E oil was added slowly through the liquid addition port in the homogenizer.
  • Proteolytic L 175 enzyme from Solvay Enzymes, Inc. of Elkhar, Indiana
  • AERPSIL R 200 silica was added via a screw feeder at a rate of about 5 lbs./hr to the drying air.
  • the resultant dry powder had a moisture of about 2%.
  • This batch was designated as P 03132843 in TABLE I below.
  • gelatin powders prepared in accordance with the teachings of the invention had considerably less odor or were substantially, odor free consistent with the lower amine content.
  • the powders of the invention also produced tablets of excel lent average hardness with greatly reduced variability from batch to batch.
  • L*, a*, b* values are set forth in TABLE 2.
  • L* is a measure of the whiteness of the final gelatin powder samples. L* is measured on a scale of 0 to 100, with 100 being the whitest. The a* and b* values represent color variations away from the white-gray-black line.
  • the gelatin powder prepared in accordance with the teachings of the invention had a higher whiteness value, and lower color deviations, than either of Hoffmann-LaRouche or Sanofi 80-90 Bloom gelatin powders.
  • the final, free-flowing gelatin-based powder of the invention is edible, and will find utility in one or more of a wide variety of end uses.
  • the free-flowing powder may be used either alone or in combination with other ingredients in a capsule product, or may be used as an additive to an animal feed product, or in foods suitable for human consumption.
  • the edible powder may be used alone or in combination with other ingredients and excipients for direct compression into tablets, especially bitamin, other nutritional, and pharmaceutical tablets.

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)

Abstract

Une poudre à base de gélatine et coulante, à caractéristiques de couleur, d'odeur et de mise en ÷uvre sous forme de comprimés améliorés, comprend une gélatine partiellement hydrolysée d'un poids moléculaire compris entre 15000 et 35000. Avant l'hydrolyse, la gélatine présente un degré de dispersion de poids moléculaire ne dépassant pas 7,0. En outre, la poudre à base de gélatine contient au moins une huile comestible obtenue à partir de vitamines solubles dans les matières grasses et d'huiles aromatisées, en particulier l'huile contenant de la vitamine E.
PCT/EP1994/003570 1993-11-02 1994-10-29 Poudres a base de gelatine a caracteristiques de couleur, d'odeur et de mise en ×uvre sous forme de comprimes ameliorees WO1995012391A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14629093A 1993-11-02 1993-11-02
US08/146,290 1993-11-02

Publications (1)

Publication Number Publication Date
WO1995012391A1 true WO1995012391A1 (fr) 1995-05-11

Family

ID=22516690

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1994/003570 WO1995012391A1 (fr) 1993-11-02 1994-10-29 Poudres a base de gelatine a caracteristiques de couleur, d'odeur et de mise en ×uvre sous forme de comprimes ameliorees

Country Status (2)

Country Link
CA (1) CA2134855C (fr)
WO (1) WO1995012391A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0062225A2 (fr) * 1981-04-06 1982-10-13 Basf Wyandotte Corporation Poudre de vitamine E obtenue par séchage à pulvérisation
WO1990003788A1 (fr) * 1988-10-14 1990-04-19 Basf Corporation Procede de production d'une poudre comestible sechee par pulverisation, s'ecoulant librement et contenant une huile

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0062225A2 (fr) * 1981-04-06 1982-10-13 Basf Wyandotte Corporation Poudre de vitamine E obtenue par séchage à pulvérisation
WO1990003788A1 (fr) * 1988-10-14 1990-04-19 Basf Corporation Procede de production d'une poudre comestible sechee par pulverisation, s'ecoulant librement et contenant une huile

Also Published As

Publication number Publication date
CA2134855A1 (fr) 1995-05-03
CA2134855C (fr) 2000-10-17

Similar Documents

Publication Publication Date Title
US6020003A (en) Method of making spray-dried powders with high edible-oil loadings based on non-hydrolyzed gelatin
JP2519008B2 (ja) 安定な熱水不溶性乾燥粉末
CN109418541B (zh) 一种斥水型脂溶性维生素微胶囊的制备方法
US8541040B2 (en) Process for producing protein microparticles
CN114680332B (zh) 一种运载苦味物质的油包水型高内相乳液及其制备方法
JP2859343B2 (ja) 油を含んで成る自由流動性噴霧乾燥食用粉末の製造法
US4911942A (en) Stabilized oil and fat powder
Kumar et al. Tea (Camellia sinensis (L.) Kuntze) as an emerging source of protein and bioactive peptides: A narrative review
US4187322A (en) Powder compositions containing vitamin C active component
CA2134855C (fr) Poudres de gelatine a caracteristiques ameliorees de couleur, d'odeur et de pressage en tablettes
BR0017192B1 (pt) processo para a preparação de biscoitos nutritivos com alto teor de proteìna.
JPH08116917A (ja) 醸造原料の製造法
EP0372669B1 (fr) Poudre d'huile ou graisse stabilisée
US3445244A (en) Solid vinegar
EP0923309B1 (fr) Aliments secs pour poissons et leur procede de preparation
US20040191390A1 (en) Encapsulated oil and fat products with free fatty acids
CN105104759A (zh) 一种用于饲料生产的纳米维生素a的制备方法
AU2002364540B2 (en) Feed additive and method for controlling large bowel fermentation in the horse and similar animals
JPH08143456A (ja) 脂溶性ビタミン類含有粉末及びその製造方法
JPH0576310A (ja) 卵黄又は全卵を含有する粉末及びその製造方法
JPH0359736B2 (fr)
US20040047977A1 (en) Precipitation process for solid sugar and oil products
JPS5942860A (ja) 芳香性顆粒状組成物の製造法
WO1995001779A1 (fr) Composition de fibres dietetiques, procede de preparation et utilisation
JPH0797339A (ja) 水溶性ヘミセルロースを含有する製剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): BR CN JP KR RU

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
122 Ep: pct application non-entry in european phase
122 Ep: pct application non-entry in european phase