Saul SMSF - Trimming Fat or Cutting Corners? Is Super Administration Cost-Cutting Focus Ultimately Costly for SMSF Trustees?
It was great to voice our concerns about the "wrap" administration software being used by fund managers and big banks in the Australian Financial Review.
Agnes King's article, "Super auditors feel the pinch and point finger at wrap 'hoarders'", talked about how institutions are using software such as Asgard Infinity and Class Super to cut superannuation administration fees to what we consider ridiculous amounts—less than $450 in some cases.
There's scope for "greater efficiencies in the sector".
But as we said in the article, saying superannuation costs are too high is like saying motor vehicle running costs are too high. How do you define that cost? Is it fuel? Registration? Mechanics? Insurance?
Kevin Bungard, the chief executive of Class Super, says there's "still a lot of fat to trim" from super administration. But while cost-cutting can be a good thing, it can also make trustees lose perspective about where to look for cost savings. Some clients paying $16,000 a year in portfolio management fees are now questioning whether they need a $50 verification certificate to confirm their bank account balances.
Yes, the software is lowering the fees. But it could also be lowering the amount of expertise the trustees are receiving.
And that could end up costing them a lot more in the long run.


Display your Spyderco pride with this high-quality T-shirt featuring our "Reliable High Performance" motto. The ultimate fashion statement for dedicated Spyderco fans.
Features: "Reliable High Performance" Motto. 100% Cotton T-Shirt. High-Density Pre-Shrunk Jersey Knit. Long-Wearing. Tubular Construction. Double-Needle Sleeves and Bottom Hems.


Film is a passion of mine that inspires me to capture images in a way that gracefully represents the world and the lives in it. It allows us to manipulate time and the way in which things happen. This can be unsettling because it suggests that nothing is as it seems or appears, which is certainly true in some if not all instances. On the other hand, it allows for the possibility to create worlds that elude the restrictions of time and place. This is what makes film beautiful and renders it art in a way that no other expression of creativity can.
This past summer I took a film production class and made three short (very short) films. Although not the first time I attempted to create short films, it was the first time I had access to professional equipment and instruction. I had attempted to make a couple little films (music videos) some years back when I was younger and less experienced, and however amateur they were, they propelled my interest of film-making. Therefore I jumped on the opportunity to take a class in which I would learn more refined techniques and be able to use better equipment. The result were two literary and historically inspired silent pieces, which although not perfect by any means, I am quite proud of. As a group project I also made a dialogue scene, which I am less enthusiastic about. But overall, they were so fun to make and certainly would not have been the same without the people in them. I really hope to make some other films, as I enjoy the whole creative, filming, and editing process so much!
I also love watching films, which is perhaps why I became interested in making films. My favorite director is Jean-Luc Godard (set aside the cliche please!) because his dialogue and symbolism are unquestionably original and inspiring. The actors in his films are also the best, Jean-Paul Belmondo & Anna Karina in particular.


text:
Statistical Report for Millennium
Product: Millennium
27 2 1 2 4 6 6 5 1 5 4.93 5
27 3 6 2 4 5 4 3 2 4.56 5
26 3 2 4 3 1 3 2 5 1 2 7 4.27 5
65 1 7 8 7 12 11 7 10 2 5 5.23 5
65 7 12 4 10 9 9 9 5 3 5.38 5
64 2 1 4 7 6 21 14 9 7 6.72 7
64 6 6 5 11 11 6 7 4 5 3 3 4.06 4
64 3 6 4 6 10 10 11 6 6 2 6 4.63 5
64 6 3 3 10 7 19 8 4 2 2 5 4.25 5
65 8 5 10 9 9 5 4 7 8 2 4.49 5
65 20 9 10 4 5 6 4 2 1 4 0 2.66 2
92 4 1 6 6 7 13 22 21 8 4 6 5.47 6
93 1 3 3 3 7 9 26 26 15 7 6.89 7
91 6 6 12 9 13 17 9 8 8 3 5 4.34 4
93 3 4 5 6 18 6 23 15 8 5 6 5.23 6
92 5 6 5 10 11 9 17 17 10 2 6 4.93 6
91 4 5 2 9 13 25 9 11 7 6 5 4.99 5
92 25 16 12 3 9 8 8 4 4 3 0 2.83 2
144 5 4 11 6 25 25 26 25 13 4 6 5.14 5
144 2 6 11 14 18 24 15 30 14 10 7 5.31 5
144 1 4 9 11 18 44 39 18 7 6.90 7
143 12 13 16 18 21 18 14 14 13 4 4 4.16 4
143 4 8 16 14 23 26 17 23 8 4 5 4.66 5
143 6 14 13 18 13 24 20 14 17 4 5 4.59 5
144 11 6 11 18 27 34 18 5 12 2 5 4.28 4
142 13 8 11 13 20 21 16 16 16 8 5 4.66 5
143 32 24 20 10 17 7 15 6 2 10 0 3.04 2
144 25 17.36%
174 5.76 44 5.84 55 5.71 20 4.85 14 5.29 6 6.67 3 2 5
174 4 1 11 12 12 20 35 52 22 5 7 5.76 6
174 3 5 20 14 14 35 52 20 11 7 5.93 6
172 2 4 5 9 20 46 56 30 8 7.22 8
170 12 12 12 12 29 52 17 13 9 2 5 4.30 5
173 17 8 9 10 18 18 25 25 23 20 6 5.24 6
174 57 22 27 13 16 11 12 4 6 6 0 2.51 2
210 3 7 14 9 31 35 58 41 12 7 6.20 7
212 1 3 2 3 9 18 55 79 42 8 7.42 8
210 13 12 9 7 20 28 20 36 36 29 7 5.68 6
208 57 24 37 17 18 22 6 11 6 10 0 2.80 2
248 2 4 4 10 11 22 50 75 55 15 7 6.44 7
246 7 11 11 21 25 43 43 45 27 13 7 5.35 6
244 59 43 19 27 18 32 14 13 7 12 0 3.00 3
393 2 3 13 7 19 29 64 118 97 41 7 6.68 7
393 1 2 7 9 24 32 58 117 103 40 7 6.74 7
389 2 7 15 14 24 32 65 103 85 42 7 6.44 7
381 10 4 7 19 37 140 55 47 39 23 5 5.51 5
388 17 7 14 13 16 39 44 71 80 87 9 6.49 7
385 105 49 45 33 35 34 32 19 15 18 0 3.00 2
454 7 2 4 10 13 37 57 141 128 55 7 6.88 7
453 6 6 16 16 22 49 58 111 122 47 8 6.50 7
437 4 5 8 14 40 178 61 56 50 21 5 5.63 5
452 13 5 16 18 24 52 50 79 93 102 9 6.55 7
386 1 4 5 18 21 30 61 106 95 45 7 6.67 7
383 19 11 11 13 17 40 39 75 69 89 9 6.40 7
342 1 7 10 31 32 108 102 51 7 7.13 7
341 1 4 13 8 17 41 47 92 71 47 7 6.58 7
315 6 3 9 8 12 136 50 47 19 25 5 5.65 5
294 5 7 10 14 37 85 100 36 8 7.08 7
302 25 8.28%
253 1 4 5 8 14 22 74 88 37 8 7.16 7
305 14 11 14 5 12 46 21 63 67 52 8 6.24 7
Library currently owns sierra (purchased prior to product release) but has had difficulty implementing it. If this is not successful we will likely begin the process of considering different paths. (Type: Academic)
Innovative Customer Support is good. However, their Sales has deteriorated significantly in the past year. It is very difficult to get a response from them. (Type: Academic)
LMS choice going forward will largely depend on our Council amalgamating with other Councils in the coming year. We will aim to share the same LMS across all libraries. (Type: Public)
Do not feel III has done enough to address new workflows resulting from increased use of electronic resources as well as traditional print materials. (Type: Academic)
We are in the middle of the tendering process so we are under confidentiality terms right now. (Type: Academic)
As a medical library we have moved to mostly electronic resources. The Millennium really doesn't handle electronic very well. Our users use the catalog less and less. We are waiting for the next version of Intota that is supposed be able to replace the ILS functions. (Type: Medical)
Millennium, and our ILS server currently located on campus, are reaching end-of-life status. We will need to migrate to Sierra (Innovative) or another ILS system. I have seen two demos of OCLC WMS and I'm not overly impressed, so far, with the product. (Type: Academic)
Our library took waaaay too long to consider migration, and our current ILS no longer meets the needs of our patrons or our collection. We are looking at a migration within the next 2 years, partly since Millennium will not be supported much longer and also because it's no longer 2007. We have only just implemented Summon in the last week (still in beta testing, really) and are considering building our next system around Summon or a similar discovery service. OCLC WorldShare would be my first choice, but if Summon proves to deliver what it promises, we could easily go with a simple (but contemporary) ILS and integrate it into discovery services rather than migrate to an entirely different LSP. (Type: Academic)
Innovative Interfaces: holding your library's data for ransom. As a for-profit company, I rate them just slightly better than airlines in terms of customer hostility. It doesn't matter the size or reputation of your library, Innovative's primary goal (other than making a profit, which in and of itself is not inherently evil) is to obfuscate and hide as much functionality as possible. (Type: Academic)
We are hosted on iii with an application service manager who handles almost all support issues. Customer service is great our sales rep not so much. (Type: Academic)
We manage print journals and electronic resources using True Serials and 360 Link, so it is hard to measure the usefulness of our ILS in this area. W may be forced to move to OpenSource if Millennium support is withdrawn in the next 3-5 years. Not sure if your items in the collection number is only print. We are increasingly using electronic journals and book collections. (Type: Academic)
We are looking for a solution that integrates the ILS with the Discovery interface. (Type: Academic)
III has improved customer service and appears interesting in working to keep current customers using their product(s), but cost is a major issue. (Type: Public)
[...] (Type: Academic)
We have stayed with Innovative and Millennium for nearly 15 years. The functionality of their product has served us well. However, Innovative is a very expensive ILS and we no longer feel like we can bear the annual costs. Features which we think ought to be offered as enhancements end up being expensive new modules that we have to purchase - usually with an additional increase to annual maintenance. Innovative would like us to move to Sierra but migration costs are also prohibitive. We feel like Innovative is pricing us out of being able to continue with their product. Innovative support has decreased dramatically. When you call the Help Desk you often have to leave a message instead of talking to a real person. Follow-up on open tickets can be slow. We had a major server crash and were down for nearly 4 1/2 days because Innovative personnel could not figure out the problem and was slow in shipping out replacement parts. Communication between the library and the customer sales rep is not always clear leading to misunderstandings which could be avoided. (Type: Public)
Dissatisfaction with our current ILS vendor reached a tipping point this year when we could not implement an expensive module because our hardware was out of warranty, but still had to pay for the module anyway due to contractual language. We have a strategic initiative to investigate ILS alternatives. We are also strengthening our in house technology skills and building close relationships with campus IT. This could allow us to implement an open source ILS in the future. I would like to see our next ILS be built around the most accurate, complete e-resource knowledge base we can find, whether this means going open source or choosing a proprietary vendor. Within the next year or two we hope to reach a decision. (Type: Academic)
The [...] may soon (1-2 years) have an opportunity to contract with a vendor for a statewide ILS offering. If this happens, many/most of the California community colleges would likely be migrating to the chosen vendor, including our college. (Type: Academic)
Encore is not as reliable as we would hope. From time to time the processes which import records and item status data from Millennium stall unexpectedly and need to be restarted. We may upgrade to Sierra, but from what we've seen, the back-end functionality is very similar to Millennium and not as up-to-date as we would like. (Type: Law)
While our current system is III's Millennium, we have signed a contract for Alma-Primo and are in the beginning stages of migration, with expected completion May 2016. (Type: Academic)
Above figure represents both campus libraries. (Type: Academic)
Support for Millennium is diminishing , we are now in the middle of a migration to Sierra and we expect improved support when we have completed the migration. (Type: Academic)
Innovative Interfaces is done. Wonder if EBSCO will buy them out? I have concerns about the venture capital company that own SirsiDynix and it doesn't appear ProQuest has a clue what to do with their Intota "product" or I should say enhanced Summons software. Seems like OCLC WMS is the only viable choice at the moment. It's interesting how the ILS industry has conflated in the last year. (Type: Academic)
Bywater support for Koha is 25% that of Millennium with no huge license fee. Staff client also entirely browser based. (Type: Medical)
We're on Innovative's Millennium. It is a terrible, unfriendly, and outdated system that does almost nothing well. We're just now researching discovery layers. Summon is a frontrunner as it performed very well in our testing and has a decent reputation. EDS and Primo look OK. Encore was eliminated quickly as it performed poorly in our testing. OCLC is pushing Worldshare which makes us uncomfortable moving to their discovery layer while not being ready to migrate ILS. (Type: Academic)
We are migrating to Sierra within a year. The only reason we are doing this is not because III or Sierra is good, it's because there are no other viable alternatives. Pennsylvania's implementation of OpenILS is incredibly limited and development has been too slow for us to take SPARK seriously. (Type: Consortium)
The Library is currently involved in an RFP process to identify and select a new ILS platform. We are relatively happy with our current ILS, but we have also been with that vendor for about 20 years. That vendor has recently introduced their "next generation" product so a major change is inevitable in the not too distant future. There have been some significant developments in the ILS marketplace during the past few years. Most of the major vendors have introduced new platforms that are primarily cloud-based SAAS services. It seems like an appropriate time to review our ILS options in a more comprehensive manner. (Type: Academic)
We wish our ILS and discovery service did a better job of putting the same book and e-book next to each other in the browse list. All too often a print book will be listed several entries away for the electronic version of the same title. (Type: Academic)
Upgrade to the latest version of Millennium will improve the ratings given here. (Type: Academic)
We get frustrated with Innovative Interfaces requirement to purchase add-on modules for functionality we think should come out of the box (i.e. mobile friendly interfaces, SMS alerts, etc.) (Type: Academic)
As a very specialized library, a discovery interface would only hinder our efforts to effectively serve our patrons. We have no interest whatsoever in obtaining one. (Type: Music)
The biggest barrier to signing up for Sierra is cost. The upgrade is very expensive and would be largely invisible to users, though it would be beneficial to staff. The cost is very high for something that is almost totally behind the scenes. We currently have products related to discovery from several vendors. I would like to select a vendor and integrate some/all of these products (link resolver, ILS, A-Z list, ERM, etc.), but it's challenging to find both time and money to take on a project of that magnitude. (Type: Academic)
I think academic medical libraries like us are in a spot regarding ILS; ILS is less important to us than to most other large academic libraries. Electronic resources are where we spend our collections budget and ILS , particularly older ILS like Millennium are not optimized for end user access to electronic resources. For the few books we buy and circulate, Millennium works OK, we know how it works for the most part and we've had it for so long it is second nature. For us, to implement (and even take the time to consider) product selection and migration is to shift our organizational focus at least temporarily to areas that are out of proportion with our library's day to day and strategic goals. Yet, due to aging ILS hardware we are grappling with these questions, and find ourselves wondering just how to stop everything else we are doing (for 4 months, or whatever) and just deal with this one issue. Although open source products like Koha could save us a lot of money, I think we acknowledge that end users' discovery of electronic resources is the most important consideration for us, and that is why we're looking very closely at Alma and Worldshare. (Type: Medical)
We have become very dissatisfied with the support service. Minor questions go unanswered, and larger problems take longer than they should to be resolved. Our library has been required to do much more follow up and elevating of problem status than should be necessary. (Type: Special)
Our ILS server is hosted through a third party organization. If it was hosted by the ILS company or brought back to campus, the outlook on customer support would likely be different. (Type: Academic)
The Innovative Interfaces should be more concerned about their customers in Taiwan. (Type: Academic)
Currently waiting on an investigation of local consortia that is looking into next generation library systems. Will move forward on new system investigation once that is completed. (Type: Academic)
We like the Intota ERM and knowledge base for eperiodicals. World share seems better for ebooks. Assessment is better by OCLC Intota is behind in dealing with acquisitions and reserves. (Type: Academic)
For the most part we, at this library, are very satisfied with Millennium and with Innovative. However, we are part of a larger [...] higher ed. consortium of public institutions and we issued an RFP for a shared new system among the 17 libraries. The consensus was that ExLibris Alma/Primo was a more technologically advanced (true multi-tenant architecture, etc.) product and that resulted in a decision to go with Ex Libris. It remains to be seen if this was a good decision or not. Implementation has not yet begun and I anticipate that it will be complicated. I also hope that from the patron perspective it will work well. I believe the IT concerns drove the decision. (Type: Academic)
It doesn't look like there are a lot of choices for a new ILS. The book circulation in our library has dropped significantly in the recent year. The new generation of ILS cannot be a system that is only good at managing print resources. I am concerned that the cost of commercial products will keep increasing. I am hoping that open source ILS can eventually manage both print and electronic resources well. (Type: Academic)
Migration to our vendor's new platform is desired but not likely within the next year. (Type: Government Agency)
Our collection in Millennium is over 300,000 records because we have loaded MARC records for Ebsco ebooks, Films on Demand streaming videos, etc. The 75,000 number is accurate for physical holdings. (Type: Academic)
Because we are part of a consortium, we have not participated in an LMS vendor selection process. This will be conducted by [...]. (Type: Museum)
Plan to migrate to Sierra soon. EDS very close to launch. Millennium impressions: WAM proxy rewrite need improvement. WebPAC not responsive. We also have Boopsie for mobile users. (Type: Academic)
We've been HAPPILY with Innovative from the early 1990's. Upgraded to Millennium early 2000's. But we're having a hard time justifying upgrading to Sierra which requires basically $40,000+ migration cost plus cost of a 2nd server. Those hosted servers would cost $17,000 yearly for starters. We already pay $40,000+ annually in "maintenance". That is a LOT. Soon paying $60,000. annually to stay III is feeling crazy and indefensible. Great business model for them, NOT for higher ed. that is inching towards unaffordableness/unsustainability. We need radically better pricing and something more rewarding than Sierra! Change may be painful but what doesn't kill us will make us stronger. ALSO: Hey Ebsco, merge with Innovative! THANKS MARSHALL! (Type: Academic)
We consider migrating to a new ILS that can both meet our technological need and budget condition. Sierra is a bit too expensive for us as a small academic library. (Type: Academic)
Library has been with same vendor since 1994 - is looking to bring itself up-to-date as to the current state of the ILS and will be considering migration to another vendor system over the next 2 years. (Type: Academic)
We may not have a choice in migrating to Sierra, although I don't want to leave Millennium. (Type: Law)

redpajama_set_name: RedPajamaCommonCrawl


text:
USE OF 4-HYDROXYCHALCONE DERIVATIVES FOR MASKING AN UPLEASANT TASTE
The use is described of the 4-hydroxychalcone derivatives of the formula (I)
A may represent a single or double bond,
R1, R2 and R3, mutually independently, may in each case mean H, OH or (preferably C1-C4) alkoxy, providing that at least one of the residues R1 to R3 means OH,
R4 means H, OH or (preferably C1-C4) alkoxy,
(ii) the salts thereof
(iii) mixtures thereof
to mask or reduce the unpleasant taste impression of an unpleasant tasting substance, as are corresponding methods and preparations.
Ley, Jakob (Holzminden, DE)
Paetz, Susanne (Hoexter, DE)
Riess, Thomas (Holzminden, DE)
Krammer, Gerhard (Holzminden, DE)
SYMRISE GmbH & Co. KG (Holzminden, DE)
A23L27/00; A61K31/12; A23L27/20
20070191431 2-Amino-5-piperidinylimidazolone compounds and use thereof for beta-secretase modulation August, 2007 Zhou et al.
20080004320 Remedy for Glomerular Disease January, 2008 Nakagawa
20030036562 Water-soluble dendrimeric fullerene as anti-HIV therapeutic February, 2003 Schinazi et al.
20080279934 EXTENDED RELEASE FORMULATION FOR PRALNACASAN November, 2008 Soennichsen et al.
20090163568 AVERMECTIN/METRONIDAZOLE COMPOSITIONS FOR TREATING AFFLICTIONS OF THE SKIN, E.G., ROSACEA June, 2009 Kaoukhov et al.
20090018173 Method for controlling the yeast-to-filamentous growth transition in fungi January, 2009 Toenjes et al.
20090082362 Use of capsaicin receptor antagonists to treat symptoms of tear gas exposure March, 2009 Bakthavatchalam et al.
20060239930 PROCESS FOR NEBULIZING AQUEOUS COMPOSITIONS CONTAINING HIGHLY CONCENTRATED INSULIN October, 2006 Lamche et al.
20040029953 Use of neuropeptide-y antagonists in treatment of alcoholism February, 2004 Hodge
20060183698 Ophthalmic formulations and uses thereof August, 2006 Abelson
20050238732 Carbonated germicide with pressure control October, 2005 Lu et al.
RAO, SAVITHA M
POLSINELLI PC (HOUSTON, TX, US)
1. Use of a 4-hydroxychalcone derivative of the formula (I) wherein A may represent a single or double bond, R1, R2 and R3, mutually independently, may in each case mean H, OH or (preferably C1-C4) alkoxy, providing that at least one of the residues R1 to R3 means OH, and R4 means H, OH or (preferably C1-C4) alkoxy, and/or a salt of such a 4-hydroxychalcone derivative of the formula (I), a mixture comprising or consisting of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, a mixture comprising or consisting of salts of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, or a mixture comprising or consisting of a 4-hydroxychalcone derivative of the formula (I) or two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, and a salt of a 4-hydroxychalcone derivative of the formula (I) or two or more salts of different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, to modify, mask or reduce the unpleasant taste impression of an unpleasant tasting substance.
2. The use as claimed claim 1, wherein in formula (I) A represents a single bond, and either R1 means OH, and R2 and R3, mutually independently, mean H or OH, or R2 means OH, and R1 and R3 mean H R4 means H or methoxy, or of a salt of such a 4-hydroxychalcone derivative.
3. The use as claimed in claim 1, of a 4-hydroxychalcone derivative of the formula (I) selected from the group consisting of 3-(4-hydroxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 1) 3-(4-hydroxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (davidigenin, compound 2) 3-(4-hydroxyphenyl)-1-(2,6-dihydroxyphenyl)propan-1-one (compound 3) 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (phloretin, compound 4) 3-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 5) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (compound 6) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,6-dihydroxyphenyl)propan-1-one (compound 7) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (compound 8) 3-(3,4-dihydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (3-hydroxy-phloretin, compound 9), 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)propan-1-one (compound 10) a salt of such a 4-hydroxychalcone derivative of the formula (I), a mixture comprising or consisting of two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group, a mixture comprising or consisting of salts of two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group or a mixture comprising or consisting of a 4-hydroxychalcone derivative of the formula (I) selected from said group or two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group and a salt of a 4-hydroxychalcone derivative of the formula (I) selected from said group or two or more salts of different 4-hydroxychalcone derivatives of the formula (I) selected from said group.
4. The use as claimed in claim 1, wherein one, several or all of the hydroxy groups of the compound of the formula (I) are deprotonated and a corresponding amount of countercations is present, the countercations being selected from the group consisting of unipositive cations of main group and subgroup I, ammonium ions, trialkylammonium ions, dipositive cations of main group and subgroup II and tripositive cations of main group and subgroup III, and mixtures thereof.
5. The use as claimed in claim 1, together with at least one lactone, to modify, mask or reduce the unpleasant taste impression of an unpleasant tasting substance.
6. The use as claimed in claim 5, wherein nonenolide and/or 4-methyl-5-hydroxyhexanoic acid lactone is additionally used.
7. The use as claimed in claim 5 to modify, mask or reduce the in particular bitter taste of a potassium salt, preferably of potassium chloride.
8. The use as claimed in claim 1 in a pharmaceutical preparation to be taken orally or a preparation serving for nutrition, oral care or pleasure.
9. The use as claimed in claim 1, wherein eriodictyol, homoeriodictyol and/or a sodium salt thereof is additionally used.
10. A preparation, comprising a) a 4-hydroxychalcone derivative of the formula (I) wherein A may represent a single or double bond, R1, R2 and R3, mutually independently, may in each case mean H, OH or (preferably C1-C4) alkoxy, providing that at least one of the residues R1 to R3 means OH, and R4 means H, OH or (preferably C1-C4) alkoxy, and/or a salt of such a 4-hydroxychalcone derivative of the formula (I), a mixture comprising or consisting of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, a mixture comprising or consisting of salts of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case the above-stated meaning, or a mixture comprising or consisting of a 4-hydroxychalcone derivative of the formula (I) or two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, and a salt of a 4-hydroxychalcone derivative of the formula (I) or two or more salts of different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, and b) one or more unpleasant tasting substances, providing that i) the 4-hydroxychalcone derivative of the formula (I) is not phloretin if the preparation contains hesperetin, phloridzin, or another phloretin glycoside, and/or that ii) if the preparation contains one or more sweet-tasting substances, the sweetness of the preparation amounts to at most 1% sucrose equivalents.
11. The preparation as claimed in claim 10, wherein in formula (I) A represents a single bond, and either R1 means OH, and R2 and R3, mutually independently, mean H or OH, or R2 means OH, and R1 and R3 mean H R4 means an H or methoxy, or a salt of such a 4-hydroxychalcone derivative.
12. The preparation as claimed in claim 10, comprising a 4-hydroxychalcone derivative of the formula (I) selected from the group consisting of 3-(4-hydroxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 1) 3-(4-hydroxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (davidigenin, compound 2) 3-(4-hydroxyphenyl)-1-(2,6-dihydroxyphenyl)propan-1-one (compound 3) 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (phloretin, compound 4) 3-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 5) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (compound 6) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,6-dihydroxyphenyl)propan-1-one (compound 7) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (compound 8) 3-(3,4-dihydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (3-hydroxy-phloretin, compound 9), 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)propan-1-one (compound 10) a salt of such a 4-hydroxychalcone derivative of the formula (I), a mixture comprising or consisting of two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group, a mixture comprising or consisting of salts of two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group or a mixture comprising or consisting of a 4-hydroxychalcone derivative of the formula (I) selected from said group or two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group and a salt of a 4-hydroxychalcone derivative of the formula (I) selected from said group or two or more salts of different 4-hydroxychalcone derivatives of the formula (I) selected from said group.
13. The preparation as claimed in claim 10, wherein the unpleasant tasting substance(s) is or are selected from the group consisting of: xanthine alkaloids; xanthines, in particular caffeine, theobromine, theophylline and methylxanthine; alkaloids, in particular quinine, brucine, strychnine, nicotine; phenolic glycosides, in particular salicin, arbutin; flavonoid glycosides, in particular neohesperidin, hesperidin, naringin, quercitrin, rutin; bitter tasting chalcones or chalcone glycosides, in particular phloridzin, hydrolyzable tannins, gallic or ellagic acid esters of carbohydrates, in particular pentagalloylglucose; non-hydrolyzable tannins, in particular galloylated catechols or epicatechols and oligomers thereof, in particular proanthyocyanidines or procyanidines, thearubigin; flavones, in particular quercetin, taxifolin, myricetin; phenols, in particular salicin; polyphenols, in particular γ-oryzanol, caffeic acid or esters thereof; terpenoid bitter substances, in particular limonoids such as limonin or nomilin from citrus fruits, lupolones and humulones from hops, iridoids, secoiridoids; absinthin; amarogentin; metal salts, in particular potassium, magnesium and calcium salts, potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate, potassium malate, sodium sulfate, magnesium sulfate; pharmaceutical active ingredients, in particular fluoroquinolone antibiotics, paracetamol, aspirin, β-lactam antibiotics, ambroxol, propylthiouracil [PROP], guaifenesin; vitamins, in particular vitamin H, vitamins from the B group, such as vitamin B1, B2, B6, B12, niacin, pantothenic acid; denatonium benzoate; sucralose octaacetate; iron salts; aluminum salts; zinc salts; urea; unsaturated fatty acids, in particular unsaturated fatty acids in emulsions; bitter tasting amino acids, in particular leucine, isoleucine, valine, tryptophan, proline, histidine, tyrosine, lysine or phenylalanine; and bitter tasting peptides, in particular peptides with an amino acid from the group leucine, isoleucine, valine, tryptophan, proline or phenylalanine at the N or C terminus.
14. The preparation as claimed in claim 10, further comprising one or more lactones, preferably nonenolide and/or 4-methyl-5-hydroxyhexanoic acid lactone.
15. The preparation as claimed in claim 10, wherein the preparation is an oral pharmaceutical preparation, a preparation serving for nutrition, a preparation serving for pleasure or a preparation serving for oral hygiene.
16. The preparation as claimed in claim 10, further comprising at least one unpleasant tasting substance, wherein the amount of the unpleasant tasting substance is sufficient to be perceived as an unpleasant taste in a comparison preparation which does not comprise any 4-hydroxychalcone derivative of the formula (I), salt or mixture of such a 4-hydroxychalcone derivative but which is otherwise of identical composition, and the quantity of the 4-hydroxychalcone derivative of the formula (I), salt or mixture of such a 4-hydroxychalcone derivative in the preparation is sufficient to organoleptically modify, mask or reduce the unpleasant taste impression of the unpleasant tasting substance as compared with the comparison preparation.
17. The preparation as claimed in claim 10, characterized in that the preparation, relative to its total weight, contains a total of 0.000001 to 95 wt. % of 4-hydroxychalcone derivative(s) and, if present, the salts thereof.
18. The preparation as claimed in claim 10, characterized in that it takes the form of a semifinished product, an odoriferous, aroma or flavoring substance composition or a seasoning mixture.
19. The preparation as claimed in claim 10, further comprising at least one further substance for modifying, masking or reducing the unpleasant taste impression of an unpleasant tasting substance.
20. A method of modifying, masking or reducing the unpleasant taste impression of an unpleasant tasting substance, comprising the step of mixing an unpleasant tasting substance with a 4-hydroxychalcone derivative of the formula (I) wherein A may represent a single or double bond, R1, R2 and R3, mutually independently, may in each case mean H, OH or (preferably C1-C4) alkoxy, providing that at least one of the residues R1 to R3 means OH, and R4 means H, OH or (preferably C1-C4) alkoxy, and/or a salt of such a 4-hydroxychalcone derivative of the formula (I), a mixture comprising or consisting of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, a mixture comprising or consisting of salts of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, or a mixture comprising or consisting of a 4-hydroxychalcone derivative of the formula (I) or two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, and a salt of a 4-hydroxychalcone derivative of the formula (I) or two or more salts of different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning.
21. The method as claimed in claim 20, wherein in formula (I) A represents a single bond, and either R1 means OH, and R2 and R3, mutually independently, mean H or OH, or R means OH, and R1 and R3 mean H R4 means an H or methoxy, or the 4-hydroxychalcone derivative is present in the form of a salt.
22. The method as claimed in claim 20, wherein the 4-hydroxychalcone derivative of the formula (I) is selected from the group consisting of 3-(4-hydroxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 1) 3-(4-hydroxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (davidigenin, compound 2) 3-(4-hydroxyphenyl)-1-(2,6-dihydroxyphenyl)propan-1-one (compound 3) 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (phloretin, compound 4) 3-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 5) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (compound 6) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,6-dihydroxyphenyl)propan-1-one (compound 7) 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (compound 8) 3-(3,4-dihydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (3-hydroxy-phloretin, compound 9), 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)propan-1-one (compound 10) the salt is a salt of such a 4-hydroxychalcone derivative of the formula (I), the mixture is a mixture comprising or consisting of two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group, the mixture is a mixture comprising or consisting of salts of two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group, or the mixture is a mixture comprising or consisting of a 4-hydroxychalcone derivative of the formula (I) selected from said group or two or more 4-hydroxychalcone derivatives of the formula (I) selected from said group and a salt of a 4-hydroxychalcone derivative of the formula (I) selected from said group or two or more salts of different 4-hydroxychalcone derivatives of the formula (I) selected from said group.
23. The method as claimed in claim 20, wherein one, several or all of the hydroxy groups of the 4-hydroxychalcone derivative of the formula (I) are deprotonated and a corresponding amount of countercations is present, the countercations being selected from the group consisting of unipositive cations of main group and subgroup I, ammonium ions, trialkylammonium ions, dipositive cations of main group and subgroup II and tripositive cations of main group and subgroup III, and mixtures thereof.
24. The method as claimed in claim 20, additionally comprising mixing of the unpleasant tasting substance with at least one lactone, preferably of nonenolide and/or 4-methyl-5-hydroxyhexanoic acid lactone.
25. The method as claimed in claim 20, wherein the unpleasant tasting substance is a bitter tasting substance, preferably a potassium salt, and particularly preferably potassium chloride.
26. The method as claimed in claim 20, additionally comprising mixing of the unpleasant tasting substance with eriodictyol, homoeriodictyol and/or a sodium salt thereof.
The invention relates to the use of specific 4-hydroxychalcone derivatives, the salts thereof and mixtures thereof for masking or diminishing unpleasant taste impressions, in particular bitter, astringent and/or metallic taste impressions. The invention additionally relates to specific preparations, which contain an effective content of the stated 4-hydroxychalcone derivatives, the salts thereof or mixtures thereof.
Foodstuffs or products consumed for pleasure frequently contain various bitter substances, which on the one hand are desirable and characteristic in moderation (for example caffeine in tea or coffee, quinine in so-called Bitter Lemon beverages, hop extracts in beer), but on the other hand may severely reduce value (for example flavonoid glycosides and limonoids in citrus juices, the bitter aftertaste left by many artificial sweeteners such as aspartame or saccharin, hydrophobic amino acids and/or peptides in cheese).
To reduce the natural content of bitter substances, subsequent treatment is therefore often necessary, for example extractive treatment such as decaffeination of tea or coffee, or enzymatic treatment, for example treatment of orange juice with a glycosidase to destroy the bitter naringin or the use of specific peptidases when ripening cheese. This treatment is a strain on the product, produces waste substances and also gives rise for example to solvent residues and other residues (enzymes) in the products.
It is therefore desirable to find substances which can effectively suppress or at least reduce unpleasant taste impressions, in particular bitter, astringent and/or metallic taste impressions.
It is particularly important to suppress the bitter taste of many pharmaceutical active ingredients, since such suppression may markedly increase the readiness of the patient, in particular in the case of patients sensitive to bitterness such as children, to take the active-ingredient containing preparation orally. Many pharmaceutical active ingredients, for example aspirin, salicin, paracetamol, ambroxol or quinine, to mention just a very small selection for clarification, have a pronounced bitter, astringent and/or metallic taste and/or aftertaste.
The increased use of potassium salts in the place of sodium salts constitutes an increasingly important masking problem. In particular, sodium chloride is now frequently replaced in spicy applications at least partially by potassium chloride, which is indeed used as a salty tasting salt but also causes a number of additional, unpleasant taste impressions and in particular is described as bitter and metallic tasting.
Although a number of substances are known which can partially suppress the bitter taste, many of them are severely limited in application.
In U.S. Pat. No. 5,637,618 a bitter taste, in particular the bitter taste of potassium salts, is reduced by means of lactisole [2O-(4-methoxyphenyl)lactic acid]. However, this inhibitor simultaneously severely inhibits the sweet taste impression (cf. U.S. Pat. No. 5,045,336), which severely limits applicability.
2,4-Dihydroxybenzoic acid potassium salt is described in U.S. Pat. No. 5,643,941 (table, column 3, line 18) as an agent for masking the bitter taste of potassium chloride or potassium salts but cannot for example suppress the taste of caffeine.
According to GB 2,380,936, suppression of the taste of bitter pharmaceuticals may be achieved using ginger extracts. However, ginger extracts are not suitable for many applications, since they produce a strong aroma impression and/or their frequently perceived spiciness is troublesome.
In U.S. Pat. No. 5,580,545, although taste-modifying properties are described for a number of flavones (2-phenylchrom-2-en-4-one), no bitterness-reducing or -suppressing effect was disclosed.
US 2002 177,576 describes the suppression of a bitter taste by nucleotides, for example cytidine 5′-monophosphate (CMP). However, these highly polar compounds, which can therefore only be used in highly polar solvents, can only be used to a very limited degree in many fatty foods. In addition, the availability of such substances is severely limited due to the complex chemical synthesis thereof.
US 2006/286276 describes mixtures of nucleotides, for example adenosine 5-monophosphate (AMP) with the amino acid taurine, which in reduced common salt applications, which simultaneously have an elevated content of potassium chloride, may at least partially reduce the bitter and metallic taste of the potassium salts.
US 2002/0188019 describes hydroxyflavanones as effective bitterness masking agents, which are difficult to obtain synthetically and are not available in large quantities at a reasonable price.
The sodium salts sodium chloride, sodium citrate, sodium acetate and sodium lactate display a bitterness-masking effect relative to many bitter substances (for example Nature, 1997, vol. 387, p. 563); however, the consumption of relatively large quantities of sodium ions may lead, for example, to cardiac/circulatory disorders. In addition, a significant bitterness-masking effect only disadvantageously comes about at relatively high sodium concentrations (from approx. 0.1 M), which corresponds for example to a generally unacceptable elevated content of approx. 0.6 wt. % NaCl in the final application (cf. R. S. J. Keast, P. A. S. Breslin and G. K. Beauchamp, Chimia 2001, 55(5), 441-447).
WO 00121390 describes polyglutamic acid as a bitterness-masking agent; relatively elevated concentrations in the range of around 1 wt. % being required here.
A lipoprotein consisting of β-lactoglobulin and phosphatidic acid, likewise displays a bitterness-masking effect (EP A 635 218). Such polymers are difficult to characterize and standardize, however, and display a pronounced soapy off-flavor.
The flavone glycoside neodiosmin [5,7-dihydroxy-2-(4-methoxy-3-hydroxyphenyl)-7-O-neohesperidosyl-chrom-2-en-4-one] likewise exhibits a bitterness-masking action (U.S. Pat. No. 4,154,862) but is distinguished by a disaccharide residue, which makes the substance much more difficult to prepare, or isolate, and use.
WO 2005/096841 proposes γ-aminobutyric acid as a bitterness-masking agent; although this is effective, it additionally gives the preparation a slightly sour taste. WO 2006/024587 describes hydroxybenzoic acid vanillyl amides as a masking agent for a bitter taste; likewise a number of short-chain ginger dione derivatives according to WO 2007/003527 and hydroxydeoxybenzoins according to WO 2006/106023, none of which occur naturally.
The primary object of the present invention was to find substances which (a) are suitable for masking or reducing the unpleasant taste impression of substances that taste unpleasant (and preferably in particular exhibit a bitterness-masking effect against a large number of bitter substances) (b) are widely usable, (c) are readily accessible and (d) ideally occur naturally.
The stated object is achieved according to the invention by the use of
of a 4-hydroxychalcone derivative of the formula (I)
and R4 means H, OH or (preferably C1-C4) alkoxy,
a salt of such a 4-hydroxychalcone derivative of the formula (I),
a mixture comprising or consisting of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning,
a mixture comprising or consisting of salts of two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning,
a mixture comprising or consisting of
a 4-hydroxychalcone derivative of the formula (I) or two or more different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning, and
a salt of a 4-hydroxychalcone derivative of the formula (I) or two or more salts of different 4-hydroxychalcone derivatives of the formula (I), wherein R1, R2, R3 and R4 in each case have the above-stated meaning,
to modify, mask or reduce the unpleasant taste impression of an unpleasant tasting substance, in particular a bitter taste or bitter aftertaste.
Unpleasant tasting substances for the purposes of the invention are:
(a) substances which taste bitter, astringent, cardboardy, dusty, dry, floury, rancid and/or metallic and
(b) substances that have a bitter, astringent, cardboardy, dusty, dry, floury, rancid or metallic aftertaste.
The above-mentioned unpleasant tasting substances may also possess further flavor and/or odor qualities which are generally not unpleasant. As further flavor qualities which are not unpleasant for the purposes of the present invention, mention may be made, for example, of spicy, umami, sweet, salty, sour, hot, cooling, warming, burning or tingling.
Substances that taste bitter, astringent, cardboardy, dusty, dry, floury, rancid or metallic are, for example: xanthine alkaloids, xanthines (caffeine, theobromine, theophylline and methylxanthine), alkaloids (quinine, brucine, strychnine, nicotine), phenolic glycosides (e.g. salicin, arbutin), flavonoid glycosides (e.g. neohesperidin, hesperidin, naringin, quercitrin, rutin), bitter tasting chalcones or chalcone glycosides (e.g. phloridzin), hydrolyzable tannins (gallic or ellagic acid esters of carbohydrates, e.g. pentagalloylglucose), non-hydrolyzable tannins (optionally galloylated catechols or epicatechols and oligomers thereof, e.g. proanthyocyanidines or procyanidines, thearubigin), flavones (e.g. quercertin, taxifolin, myricetin), phenols such as for example salicin, polyphenols (e.g. γ-oryzanol, caffeic acid or esters thereof), terpenoid bitter substances (e.g. limonoids such as limonin or nomilin from citrus fruits, lupolones and humulones from hops, iridoids, secoiridoids), absinthin from wormwood, amarogentin from gentian, metal salts (in particular potassium, magnesium and calcium salts, potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate, potassium malate, sodium sulfate, magnesium sulfate), pharmaceutical active ingredients (e.g. fluoroquinolone antibiotics, paracetamol, aspirin, β-lactam antibiotics, ambroxol, propylthiouracil [PROP], guaifenesin), vitamins (for example vitamin H, vitamins from the B group, such as vitamin B1, B2, B6, B12, niacin, pantothenic acid), denatonium benzoate, sucralose octaacetate, iron salts, aluminum salts, zinc salts, urea, unsaturated fatty acids, in particular unsaturated fatty acids in emulsions, bitter tasting amino acids (e.g. leucine, isoleucine, valine, tryptophan, proline, histidine, tyrosine, lysine or phenylalanine) and bitter tasting peptides (in particular peptides having an amino acid from the group ieucine, isoleucine, valine, tryptophan, proline or phenylalanine at the N- or C-terminus). Preferred substances which taste bitter, astringent, cardboardy, dusty, dry, floury, rancid or metallic are caffeine, theobromine and theophylline, quinine, salicin, arbutin, neohesperidin, naringin, quercitrin, rutin, phloridzin, gallic or ellagic acid esters of carbohydrates (e.g. pentagalloylglucose), optionally galloylated catechols or epicatechols, proanthyocyanidines or procyanidines, thearubigin, quercetin, taxifolin, myricetin, γ-oryzanol, caffeic acid or esters thereof (e.g. chlorogenic acid and isomers), limonoids such as limonin or nomilin from citrus fruits, lupolones and humulones from hops, absinthin from wormwood, amarogentin from gentian, metal salts (in particular potassium, magnesium and calcium salts, potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate, potassium malate, sodium sulfate, magnesium sulfate) and pharmaceutical active ingredients (e.g. fluoroquinolone antibiotics, paracetamol, aspirin, β-lactam antibiotics, ambroxol, propylthiouracil [PROP], guaifenesin).
Substances that have a bitter, astringent, cardboardy, chalky, dusty, dry, floury, rancid or metallic aftertaste may be aroma substances or flavorings having a not unpleasant primary flavor (for example sweet, salty, spicy, sour) and/or odor and may belong, for example, to the group comprising sweeteners, sugar substitutes or aroma substances. Examples which may be mentioned are: potassium salts (in particular potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate, potassium malate), aspartame, neotame, superaspartame, saccharin, sucralose, tagatose, monellin, stevioside, rebaudioside, hernandulcin, thaumatin, miraculin, glycyrrhizin, glycyrrhetinic acid or derivatives thereof, cyclamate or the pharmaceutically acceptable salts of the above-mentioned compounds.
Particularly preferably, the 4-hydroxychalcone derivatives of the formula (I) according to the invention, the salts and mixtures thereof are used to modify, reduce or mask a bitter taste.
Preference is given to use of the 4-hydroxychalcone derivatives of the formula (I)
A represents a single bond,
R1 means OH
R2 and R3, mutually independently, may mean H or OH,
R4 means an H or methoxy,
and/or the salts and mixtures thereof as described above.
Preference is likewise given to use of the 4-hydroxychalcone derivatives of the formula (I)
R1 and R3 mean H,
Particularly preferred 4-hydroxychalcone derivatives of the formula (I) are:
2′,4-dihydroxydihydrochalcone or 3-(4-hydroxyphenyl)-1-(2-hydroxyphenyl)-propan-1-one (compound 1)
2′,4,4′-trihydroxydihydrochalcone or 3-(4-hydroxyphenyl)-1-(2,4-dihydroxyphenyl)-propan-1-one (davidigenin, compound 2)
2′,4,6′-trihydroxydihydrochalcone or 3-(4-hydroxyphenyl)-1-(2,6-dihydroxyphenyl)-propan-1-one (compound 3)
2′,4,4′,6′-tetrahydroxydihydrochalcone or 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxy-phenyl)propan-1-one (phloretin, compound 4)
2′,4-dihydroxy-3-methoxydihydrochalcone or 3-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxyphenyl)propan-1-one (compound 5)
2′,4,4′-trihydroxy-3-methoxydihydrochalcone or 3-(4-hydroxy-3-methoxyphenyl)-1-(2,4-dihydroxyphenyl)propan-1-one (compound 6)
2′,4,4′,6′-tetrahydroxy-3-methoxydihydrochalcone or 3-(4-hydroxy-3-methoxy-phenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (compound 8)
2′,3,4,4′,6′-tetrahydroxydihydrochalcone or 3-(3,4-dihydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (3-hydroxyphloretin, compound 9)
4,4′-dihydroxy-3-methoxy-dihydrochalcone or 3-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)propan-1-one (compound 10)
and the salts and mixtures thereof as described above.
Although compounds of the general formula (I), where A denotes a single bond, are already mentioned as such in WO 2007/014879, the fact that they may be used to modify, mask or reduce the unpleasant taste of an unpleasant tasting substance was not known. The compounds are only described together with hesperetin, which should be used to enhance a sweet taste.
Compounds 1 to 10 are listed again in the following Figure for the purpose of clarification (the general numbering scheme for dihydrochalcones is indicated by way of example on compound 1):
In salts of a compound of the above formula (I) to be used according to the invention (wherein the above-stated continues to apply with regard to the preferred meanings of the residues and variables) one, several or all of the hydroxy groups of compound (I) are deprotonated. A corresponding amount of countercations is then present, this preferably being selected from the group consisting of: unipositive cations of main group and subgroup I, ammonium ions, trialkylammonium ions, dipositive cations of main group and subgroup II and tripositive cations of main group and subgroup III, and mixtures thereof.
It goes without saying that the number of hydroxy groups in the underlying 4-hydroxychalcone derivatives is decisive with regard to the maximum degree of deprotonation and thus also to the amount of countercations present. If, for example, a total of two hydroxy groups are present in the underlying 4-hydroxychalcone derivatives, in the case of complete deprotonation of the hydroxy groups a dinegative anion is present, such that a corresponding number of positive charges has to be provided by the countercation(s).
Particularly preferred cations are Na+, K+, NH4+, Ca2+, Mg2+, Al3+ and Zn2+.
It goes without saying that the various 4-hydroxychalcone derivatives and the salts thereof may in each case be used according to the invention alone or as mixtures.
Use according to the invention is also preferred in which, in addition to a compound of the formula (I), a corresponding salt or a corresponding mixture, a further substance is present for modifying, masking or reducing the unpleasant taste impression of an unpleasant tasting substance. A combination of at least two taste-correcting agents is then present.
The known neohesperidin dihydrochalcone displays a bitterness-reducing effect, which is attributable above all, however, to its property as a very strong sweetener (cf. Manufacturing Chemist 2000, July issue, pp. 16-17), and also has a troublesome effect in non-sweet applications. From our own investigations it is clear, however, that the 4-hydroxydihydrochalcone derivatives to be used according to the invention of the formula (I) or the salts thereof, such as for example phloretin (compound 4), have only very weak inherent sweetness compared with typical sweet-tasting substances. According to the invention, the 4-hydroxychalcone derivatives of the formula (I) are not used as sweeteners. In addition, the 4-hydroxychalcone derivatives of the formula (I) have further weak intrinsic flavor characteristics which are not sweet (cf. organoleptic profile description in Examples 1-4). No bitterness-masking effect of the at most slightly sweet 4-hydroxychalcone derivatives of the formula (I) or the salts thereof has been described before.
With regard to the occurrence and synthesis of the 4-hydroxychalcone derivatives of the formula (I) used according to the invention, reference is made to U.S. 60/784,444 (now WO 2007/107596). This document as a priority document for WO 2007/014879 is accessible by file inspection and is here referred to in its entirety for the purpose of full disclosure of the present invention.
It has surprisingly been found that the 4-hydroxychalcone derivatives of the formula (I) used according to the invention, even in very low concentrations, may reduce or even completely suppress the unpleasant taste impression, in particular the bitter taste impression, of a high number of substances, in particular of caffeine, theobromine and theophylline, quinine, salicin, arbutin, neohesperidin, naringin, quercitrin, rutin, phloridzin, gallic or ellagic acid esters of carbohydrates (e.g. pentagalloylglucose), optionally galloylated catechols or epicatechols, proanthyocyanidines or procyanidines, thearubigin, quercetin, taxifolin, myricetin, γ-oryzanol, caffeic acid or esters thereof (e.g. chlorogenic acid and isomers), limonoids such as limonin or nomilin from citrus fruits, lupolones and humulones from hops, absinthin from wormwood, amarogentin from gentian, metal salts (in particular potassium, magnesium and calcium salts, potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate, potassium malate, sodium sulfate, magnesium sulfate) and pharmaceutical active ingredients (e.g. fluoroquinolone antibiotics, paracetamol, aspirin, β-lactam antibiotics, ambroxol, propylthiouracil [PROP], guaifenesin), it being particularly advantageous for the 4-hydroxychalcone derivatives used according to the invention to have virtually no intrinsic flavor and to have no negative influence on the other, as a rule not unpleasant flavor qualities, and in particular even to have a positive influence on the sweet taste of sweet substances
Surprisingly, it has further been found that the 4-hydroxychalcone derivatives of the formula (I) used according to the invention particularly effectively reduce the bitter taste, above all of potassium salts (in particular potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate or potassium malate), especially of potassium chloride, in combination with one or more lactones, preferably lactones with a 5- or 6-membered ring, particularly preferably in combination with nonenolide and/or 4-methyl-5-hydroxy-hexanoic acid lactone (4-methyl-delta-hexylactone). In this case, the bitter taste impression of the potassium salts is actually reduced and not for instance overlaid with another, stronger (e.g. sweet) taste impression.
Nonenolide may preferably be used as the (R) — or (S)-enantiomer or in racemic form. 4-Methyl-5-hydroxy-hexanoic acid lactone may be syn- or anti-configured, or be present as an (R,R)-configured enantiomer, (R,S)-configured enantiomer, (S,R)-configured enantiomer, (S,S)-configured enantiomer or as any desired mixture of the enantiomers, in particular as a racemate, or indeed as any desired mixture of the corresponding diastereomers.
As already mentioned, one aspect of the present invention relates to use of a 4-hydroxychalcone derivative of the formula (I) or of a corresponding salt or mixture for masking or reducing the unpleasant taste impression of an unpleasant tasting substance, i.e. as taste-correcting agent. Preferably, the 4-hydroxychalcone derivative of the formula (I) to be used according to the invention, the salt or the mixture are used in a pharmaceutical preparation customized to be taken orally or a preparation serving for nutrition, oral care or pleasure, the preparation conventionally comprising one or more unpleasant tasting substances.
Insofar as the present invention relates to preparations, those preparations which contain phloretin and a) hesperetin and/or b) phloridzin, or another phloretin glycoside, are preferably excepted. Excepted preparations are therefore preferably those which naturally contain the 4-hydroxychalcone derivatives according to the invention of the formula (I) and to which the 4-hydroxychalcone derivatives of the formula (I) are not added from other sources (synthetic or isolated from natural sources) above and beyond the natural quantity. These include in particular many apple-containing preparations (Malus ssp.).
If the preparation according to the invention has one or more sweet substances, it is likewise preferred for the sweetness of the preparation according to the invention to have at most 1% sucrose equivalents. Such a preparation according to the invention then has a sweetness which is no greater than that of a 1% sucrose solution. Such solutions are conventionally experienced as not tasting even slightly sweet. In the case of these preparations in particular, the reduction, modification or masking of an unpleasant, in particular a bitter, taste of an unpleasant tasting substance is clearly not attributable to covering the unpleasant taste with the very strong sweetness of the preparation.
Preparations according to the invention preferably comprise 0.000001 wt. % to 95 wt. %, relative to the total weight of the preparation, of a compound to be used according to the invention of the formula (I) (see above), a corresponding salt or mixture. In addition, one or more unpleasant tasting substances are usually present.
Particularly preferred preparations according to the invention are those which comprise at least one unpleasant tasting substance, the amount of the unpleasant tasting substance being sufficient to be perceived as an unpleasant taste in a comparison preparation which does not comprise any 4-hydroxychalcone derivative of the formula (I), salt or mixture of such a 4-hydroxychalcone derivative but which is otherwise of identical composition, and the quantity of the 4-hydroxychalcone derivative of the formula (I), salt or mixture of such a 4-hydroxychalcone derivative in the preparation is sufficient to organoleptically modify, mask or reduce the unpleasant taste impression of the unpleasant tasting substance as compared with the comparison preparation.
Preparations according to the invention may take the form of a semifinished product, an odoriferous, aroma or flavoring substance composition or a seasoning mixture.
Preparations serving for nutrition or for pleasure for the purposes of the invention are for example bakery products (for example bread, dry biscuits, cakes, other pastry products), confectionery (for example chocolates, chocolate bar products, other bar products, fruit gums, hard and soft caramels, chewing gum), alcoholic or non-alcoholic beverages (for example coffee, tea, wine, beverages containing wine, beer, beverages containing beer, liqueurs, spirits, brandies, fruit-containing carbonated beverages, isotonic beverages, soft drinks, nectars, fruit and vegetable juices, fruit or vegetable juice preparations), instant beverages (for example instant cocoa beverages, instant tea beverages, instant coffee beverages), meat products (for example ham, fresh or cured sausage preparations, spiced or marinated fresh or cured meat products), eggs or egg products (dried egg, egg white, egg yolk), cereal products (for example breakfast cereals, muesli bars, precooked ready rice products), dairy products (for example milk beverages, milk ice cream, yoghurt, kefir, curd cheese, soft cheese, hard cheese, dried milk powder, whey, butter, buttermilk, partially or fully hydrolyzed milk protein-containing products), products made from soy protein or other soybean fractions (for example soy milk and products made therefrom, soy lecithin-containing preparations, fermented products such as tofu or tempe or products made therefrom), fruit preparations (for example jams, fruit ice cream, fruit sauces, fruit fillings), vegetable preparations (for example ketchup, sauces, dried vegetables, deep-frozen vegetables, precooked vegetables, preserved vegetables), snack articles (for example baked or fried potato chips or potato dough products, maize- or peanut-based extrudates), fat- or oil-based products or emulsions thereof (for example mayonnaise, remoulade, dressings), other ready-to-serve meals and soups (for example dried soups, instant soups, precooked soups), spices, seasoning mixtures and in particular powdered seasonings, which are for example used in snack food applications. The preparations for the purposes of the invention may also be used as semifinished products for the production of further preparations serving for nutrition or for pleasure. The preparations for the purposes of the invention may also be nutritional supplements in the form of capsules, tablets (uncoated and coated tablets, for example coatings resistant to gastric juices), sugar-coated tablets, granules, pellets, mixtures of solids, dispersions in liquid phases, as emulsions, as powders, as solutions, as pastes or as other swallowable or chewable preparations.
Preparations according to the invention serving for oral care are in particular oral and/or dental care products such as toothpastes, tooth gels, tooth powders, mouthwashes, chewing gum and other oral care products.
Further conventional active ingredients, basic materials, auxiliary substances and additives for preparations serving for nutrition, for oral care or for pleasure or used may be present in quantities of 5 to 99.999999 wt. %, preferably of 10 to 80 wt. %, relative to the total weight of the preparation. The preparations may furthermore comprise water in a quantity of up to 99.999999 wt. %, preferably of 5 to 80 wt. %, relative to the total weight of the preparation.
The preparations according to the invention, containing one or more of 4-hydroxychalcone derivatives used according to the invention of the formula (I) or the salts thereof or mixtures, produced according to a preferred development by incorporating the 4-hydroxychalcone derivatives of the formula (I) or the salts thereof or mixtures as the substances themselves, as a solution or in the form of a mixture with a solid or liquid carrier in an oral pharmaceutical base-preparation or a base preparation serving for nutrition, oral care or pleasure. Preparations according to the invention in the form of a solution may advantageously also be converted into a solid preparation by spray drying.
According to a further preferred embodiment, preparations according to the invention may be produced by incorporating the 4-hydroxychalcone derivative(s) used according to the invention of the formula (I) or the salts or mixtures thereof and optionally other constituents of the preparation according to the invention into emulsions, into liposomes, for example starting from phosphatidyl choline, into microspheres, into nanospheres or also into capsules, granules or extrudates prepared from a matrix suitable for foodstuffs and products consumed for pleasure, for example prepared from starch, starch derivatives, cellulose or cellulose derivatives (for example hydroxypropylcellulose), other polysaccharides (for example alginate), natural fats, natural waxes (for example beeswax, carnauba wax) or from proteins, for example gelatin.
In a further preferred production method, the 4-hydroxychalcone derivatives of the formula (I) or the salts or mixtures thereof are previously complexed with one or more suitable complexing agents, for example with cycloglycans, for example cyclofructans, cyclodextrins or cyclodextrin derivatives, preferably α-, γ- and β-cyclodextrin, and used in this complexed form.
One preparation which is particularly preferred according to the invention is one in which the matrix is so selected that the 4-hydroxychalcone derivatives of the formula (I) are released by the matrix in delayed manner, such that a longlasting action is obtained.
The further constituents for preparations according to the invention may comprise conventional basic materials, auxiliary substances and additives for foodstuffs or products consumed for pleasure. Some of these substances have an unpleasant taste in the sense of the definition given above.
Examples of conventional basic materials, auxiliary substances and additives for foodstuffs or products consumed for pleasure are water, mixtures of fresh or processed, plant or animal basic or raw materials (for example raw, roasted, dried, fermented, smoked and/or boiled meat, bone, cartilage, fish, vegetables, fruit, herbs, nuts, vegetable or fruit juices or pastes or mixtures thereof), digestible or non-digestible carbohydrates (for example sucrose, maltose, fructose, glucose, dextrins, amylose, amylopectin, inulin, xylans, cellulose), sugar alcohols (for example sorbitol), natural or hardened fats (for example tallow, lard, palm fat, coconut oil, hardened vegetable fat), oils (for example sunflower oil, peanut oil, maize germ oil, olive oil, fish oil, soya oil, sesame oil), fatty acids or the salts thereof (for example potassium stearate), proteinogenic or non-proteinogenic amino acids and related compounds (for example taurine), peptides, native or processed proteins (for example gelatin), enzymes (for example peptidases), nucleic acids, nucleotides, taste-correcting agents for unpleasant taste impressions other than those used according to the invention (4-hydroxychalcone derivatives of the formula (I) and lactones as described above), taste-correcting agents for further generally not unpleasant taste impressions, flavor-modulating substances (for example inositol phosphate, nucleotides such as guanosine monophosphate, adenosine monophosphate or other substances such as sodium glutamate or 2-phenoxypropionic acid), emulsifiers (for example lecithins, diacylglycerols), stabilizers (for example carrageenan, alginate), preservatives (for example benzoic acid, sorbic acid), antioxidants (for example tocopherol, ascorbic acid), chelating agents (for example citric acid), organic or inorganic acidulants (for example malic acid, acetic acid, citric acid, tartaric acid, phosphoric acid), additional bitter substances (for example quinine, caffeine, limonin, amarogentin, humolone, lupolone, catechins, tannins), sweeteners (for example saccharin, cyclamate, aspartame, neotame), mineral salts (for example sodium chloride, potassium chloride, magnesium chloride, sodium phosphates), substances preventing enzymatic browning (for example sulfite, ascorbic acid), essential oils, plant extracts, natural or synthetic dyes or coloring pigments (for example carotenoids, flavonoids, anthocyans, chlorophyll and the derivatives thereof), spices, trigeminally active substances (i.e. substances which are hot, pungent, tingly, rough, astringent or cause hot or cold effects) or plant extracts containing such trigeminally active substances, synthetic, natural or nature-identical aroma substances or odoriferous substances and odor-correcting agents.
Dental care products (as the basis for preparations serving for oral care) which contain the 4-hydroxychalcone derivatives to be used according to the invention of the formula (I), the salts or mixtures thereof generally comprise an abrasive system (abrasive or polishing agent), such as for example silicas, calcium carbonates, calcium phosphates, aluminum oxides and/or hydroxyapatites, surface-active substances such as for example sodium lauryl sulfate, sodium lauryl sarcosinate and/or cocamidopropyl betaine, humectants such as for example glycerol and/or sorbitol, thickeners, such as for example carboxymethylcellulose, polyethylene glycols, carrageenan and/or Laponite®, sweeteners, such as for example saccharin, other taste-correcting agents for unpleasant taste impressions, taste-correcting agents for further generally not unpleasant taste impressions, flavor-modulating substances (for example inositol phosphate, nucleotides such as guanosine monophosphate, adenosine monophosphate or other substances such as sodium glutamate or 2-phenoxypropionic acid), cooling active ingredients such as for example menthol, menthol derivatives (for example L-menthol, L-menthyl lactate, L-menthyl alkylcarbonates, menthone ketals, menthane carboxamides), 2,2,2-trialkylacetamides (for example 2,2-diisopropyl propionic acid methylamide), icilin derivatives, stabilizers and active ingredients, such as for example sodium fluoride, sodium monofluorophosphate, tin difluoride, quaternary ammonium fluorides, zinc citrate, zinc sulfate, tin pyrophosphate, tin dichloride, mixtures of different pyrophosphates, triclosan, cetylpyridinium chloride, aluminum lactate, potassium citrate, potassium nitrate, potassium chloride, strontium chloride, hydrogen peroxide, aromas and/or sodium bicarbonate or odor-correcting agents).
Chewing gums (as a further example of the preparations serving for oral care) which contain 4-hydroxychalcone derivatives to be used according to the invention generally comprise a chewing gum base, i.e. a chewable mass which becomes plastic on chewing, sugars of various kinds, sugar substitutes, sweeteners, sugar alcohols, other taste-correcting agents for unpleasant taste impressions, taste-correcting agents for further, generally not unpleasant taste impressions, flavor-modulating substances (for example inositol phosphate, nucleotides such as guanosine monophosphate, adenosine monophosphate or other substances such as sodium glutamate or 2-phenoxypropionic acid), the cooling active ingredients, humectants, thickeners, emulsifiers, aromas and stabilizers or flavor-correcting agents mentioned in the above paragraph.
Preferably, the preparations according to the invention may also contain an aroma composition in order to round off and refine the flavor and/or odor of the preparation. Suitable aroma compositions contain for example synthetic, natural or nature-identical aroma, odoriferous and flavor substances and suitable auxiliary substances and carriers.
Preparations according to the invention which serve as semifinished products generally contain 0.0001 wt. % to 95 wt. %, preferably 0.001 to 80 wt. %, but in particular 0.01 wt. % to 50 wt. %, relative to the total weight of the preparation, of 4-hydroxychalcone derivatives to be used according to the invention of the formula (I), the salts thereof or mixtures thereof. Preparations according to the invention which are present as semifinished products may serve to mask or reduce the unpleasant taste impression of finished product preparations which are produced using the semifinished product preparation.
In a particularly preferred embodiment of the invention, the 4-hydroxychalcone derivatives according to the invention of the formula (I), the salts or mixtures thereof are used in the preparations according to the invention in combination with at least one further (other) substance to modify, mask or reduce the unpleasant taste impression of an unpleasant tasting substance. In this way, particularly active masking may be achieved.
The further taste-correcting agents may be selected from the following list, without the invention being limited thereto: nucleotides (for example adenosine 5′-monophosphate, cytidine 5′-monophosphate, inosine 5′-monophosphate) or the pharmaceutically acceptable salts thereof, lactisole, 2,4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, sodium salts (for example sodium chloride, sodium lactate, sodium citrate, sodium acetate, sodium gluconate), hydroxyflavanones (for example eriodictyol, homoeriodictyol or the sodium salts thereof, in particular according to EP 1 258 200, hydroxybenzoic acid amide (for example 2,4-dihydroxybenzoic acid vanillylamide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 2,4,6-trihydroxybenzoic acid N-(4-hydroxy-3-methoxy-benzyl)amide, 2-hydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 4-hydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide monosodium salt, 2,4-dihydroxybenzoic acid N-2-(4-hydroxy-3-methoxyphenyl)ethylamide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-ethoxybenzyl)amide, 2,4-dihydroxybenzoic acid N-(3,4-dihydroxybenzyl)amide and 2-hydroxy-5-methoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]amide (aduncamide), 4-hydroxybenzoic acid vanillylamide), hydroxydeoxybenzoins (for example 2-(4-hydroxy-3-methoxyphenyl)-1-(2,4,6-trihydroxyphenyl)ethanone, 1-(2,4-dihydroxyphenyl)-2-(4-hydroxy-3-methoxy-phenyl)ethanone, 1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxy-phenyl)ethanone, hesperetin according to WO 2007/014879, diacetyl trimers according to WO 2006/058893, deoxybenzoins according to WO 2006/106023, ginger diones according to WO 2007/003527, mixtures for amplifying salty taste according to PCT/EP 2006/067120 and documents based thereon, amino acids (for example gamma aminobutyric acid, taurine, beta-alanine, arginine, ornithine, lysine), divanillin according to WO 2004/078302, pellitorines according to WO 2004/043960 and WO 20041000787, lactones as mentioned above, preferably nonenolide and/or 4-methyl-5-hydroxy-hexanoic acid lactone or mixtures thereof, or mixtures of whey proteins with lecithins.
Particularly preferred taste-correcting agents are 2,4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, sodium lactate, sodium citrate, sodium acetate, sodium gluconate, hydroxyflavanones (for example eriodictyol, homoeriodictyol or the sodium salts thereof), in particular according to EP 1 258 200, hydroxybenzoic acid amide (for example 2,4-dihydroxybenzoic acid vanillylamide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 2,4,6-trihydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 2-hydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 4-hydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-methoxy-benzyl)amide monosodium salt, 2,4-dihydroxybenzoic acid N-2-(4-hydroxy-3-methoxyphenyl)ethylamide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-ethoxy-benzyl)amide, 2,4-dihydroxybenzoic acid N-(3,4-dihydroxybenzyl)amide and 2-hydroxy-5-methoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]amide (aduncamide), 4-hydroxybenzoic acid vanillylamide), hydroxydeoxybenzoins (for example 2-(4-hydroxy-3-methoxyphenyl)-1-(2,4,6-trihydroxyphenyl)ethanone, 1-(2,4-dihydroxyphenyl)-2-(4-hydroxy-3-methoxyphenyl)ethanone, 1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxyphenyl)ethanone, hesperetin according to WO 2007/014879, diacetyl trimers according to WO 2006/058893, deoxybenzoins according to WO 2006/106023, ginger diones according to WO 2007/003527, divanillin according to WO 2004/078302, pellitorines according to WO 2004/043960 and WO 2004/000787, lactones as mentioned above, preferably nonenolide and/or 4-methyl-5-hydroxy-hexanoic acid lactone or mixtures thereof.
Particularly preferred are hydroxy flavanones (for example eriodictyol, homoeriodictyol or the sodium salts thereof), in particular according to EP 1 258 200, 2,4-dihydroxybenzoic acid vanillylamide, 2,4,6-trihydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide, 2,4-dihydroxybenzoic acid N-(4-hydroxy-3-methoxybenzyl)amide monosodium salt, hesperetin according to WO 2007/014879, diacetyl trimers according to WO 2006/058893, ginger dione [2] according to WO 2007/003527, divanillin according to WO 2004/078302, trans-pellitorine according to WO 2004/043960 and WO 2004/000787, lactones as mentioned above, preferably nonenolide and/or 4-methyl-5-hydroxy-hexanoic acid lactone or mixtures thereof.
In a further, particularly preferred embodiment of the invention, the 4-hydroxychalcone derivatives according to the invention of the formula (I), the salts or mixtures thereof, optionally together with the above-stated further taste-correcting agents, are used in combination with one or more substances which have an unpleasant aftertaste with a not unpleasant primary flavor (for example sweet, salty, spicy, sour), preparations according to the invention being obtained which may also serve to produce ready-to-eat preparations in which the unpleasant aftertaste of the unpleasant tasting substances is then masked or reduced. In these preparations, substances used which have an unpleasant aftertaste with a not unpleasant primary flavor are above all potassium salts (in particular potassium chloride, potassium gluconate, potassium carbonate, potassium sulfate, potassium lactate, potassium glutamate, potassium succinate or potassium malate), aspartame, neotame, superaspartame, saccharin, sucralose, tagatose, monellin, stevioside, rebaudioside, hernandulcin, thaumatin, miraculin, glycyrrhizin, glycyrrhetinic acid or derivatives thereof, cyclamate or the pharmaceutically acceptable salts of the above-mentioned compounds.
The examples serve to clarify the invention, without limiting the scope of protection of the claims.
Phloretin, Compound 4
Commercial phloretin (Sigma-Aldrich, order no. P 7912, CA no. 60-82-2, purity >98%) was used.
Organoleptic profile in 5 wt. % aqueous sugar solution (sucrose):
sweet, astringent, dusty-dry
Compound 6, 2′,4,4′-trihydroxy-3-methoxydihydrochalcone
Synthesis was described in U.S. 60/784,444, Example 3.
relatively neutral, slight syrupy note
Compound 10, 4,4′-dihydroxy-3-methoxydihydrochalcone
Synthesis proceeded in a manner similar to that described in U.S. 60/784,444, Example 3.
Example of Application 1: Reducing Bitterness of a Bitter Substance Solution
In order to quantify the reduction in the bitter impression, the bitterness of an aqueous bitter substance solution and a sample containing the same quantity of bitter substance and a varying quantity of the exemplary compound, was determined by a panel of experts (rating 0 [not bitter] to 10 [extremely bitter]). Evaluation took place by calculating the reduction (in %) in the bitter impression from the average values of the assessments of the bitter substance solution or the solutions containing bitter substance and exemplary compound. 274-Dihydroxybenzoic acid (2,4-DHB) was used as a comparison from U.S. Pat. No. 5,643,941.
Bitterness of a bitter substance solution and of a solution containing bitter
substance and an exemplary compound (2,4-DHB = 2,4-dihydroxybenzoic acid).
Bitter impression % reduction
Bitter Tester (1-10) in bitter
Substance substance Total positive without with impression
100 ppm 500 ppm 15 9 5.1 ± 1.0 5.0 ± 1.0 3%, n.s.
2,4-DHB caffeine
50 ppm 500 ppm 16 13 5.5 ± 0.9 3.9 ± 1.8 28%, p < 0.05
Compound 4, caffeine
30 ppm 5 ppm 15 10 3.9 ± 2.2 2.0 ± 1.4 25%, n.s.
Compound 4, quinine
phloretin hydro-
30 ppm 250 ppm 15 10 7.3 ± 2.0 6.0 ± 1.8 18%, p < 0.1
Compound 4, salicin
Compound 6, 500 ppm 15 11 4.4 ± 1.1 3.3 ± 0.7 24%, n.s.
2′,4,4′- caffeine
trihydroxy-3-
methoxydihydro-
chalcone
Compound 10, caffeine
4,4′-dihydroxy-
3-methoxy-
dihydrochalcone
50 ppm 5 ppm 13 11 3.6 ± 1.0 2.4 ± 0.8 34%, p < 0.1
Compound 10, quinine
4,4′-dihydroxy- hydro-
3-methoxy- chloride
"Tester positive" means the number of testers who were able to identify masking;
the 95% confidence ranges are stated as errors;
p < x means the significance according to Student's t-test method (cf. statistics textbooks),
n.s. means not significant.
Example of Application 2: Reduction in Unpleasant Taste Impressions of Potassium Chloride-Containing Preparations
A fat- and common salt-free meat stock is prepared with 0.4 wt. % sodium chloride and 0.4 wt. % potassium chloride (in each case relative to total weight) (comparison solution A). The same solution is prepared again and a quantity of phloretin (compound 4 from Example 1) is added. Solution A is served up to the testers once with the designation "standard solution", and at the same time solution A and solution B are served up as "test solution 1" or "test solution 2" in a random order unknown to the respective tester (i.e. solutions A and B may have different designations for different testers; each tester has to test three solutions). In a first test phase, the testers are asked whether one of the three solutions tastes different from the other two (triangle difference testing). If the response to this question is "No", the test is stopped for that tester. If the response to this question is "Yes", the tester has to quantify the flavor qualities, listed below, of "test solution 1" or "test solution 2" deviating from the "standard solution" (relative to the "standard solution", 0 flavor quality identical to the standard, −4 very much weaker than the standard, +4 very much stronger than the standard). Taking as basis the results from all the testers, the average of all deviations from the "standard solution" is calculated for the individual flavor qualities.
Mouth of Positive
Substance Salty Sweet Sour Bitter fullness Aromaticity testers testers
Phloretin −0.7 0.9 0.1 −0.4 0.3 −0.1 21 16 (p < 0.05)
(compound
Example 1),
Although the exemplary application is somewhat less salty and sweeter than the "standard solution", it displays a significantly less bitter aftertaste and is therefore preferred.
Example of Application 3: Spray-Dried Preparation as Semifinished Product for Aromatization of Finished Products
Constituent in wt. %
Drinking water 60.8%
Maltodextrin from wheat 24.3%
Gum arabic 6.1%
Phloretin (compound 4 from Example 1) 8.8%
The drinking water is initially introduced into a container and the maltodextrin and gum arabic are dissolved therein. Then the phloretin (Example 1; compound 4) is emulsified into the carrier solution with a Turrax. The temperature of the spray solution should not exceed 30° C. The mixture is then spray-dried (specified inlet temperature: 185-195° C., specified outlet temperature: 70-75° C.). The spray-dried semifinished product contains approx. 18-22% of the active ingredient from Example 2.
Spray-dried preparations may likewise be produced as semifinished products from Example 2 (compound 6).
Example of Application 4: Black Tea Preparation
Black tea, Ceylon, leaf 94.00%
Semifinished product from Example of application 2, 6%
containing approx. 18-22% phloretin (compound 4 from
Example 1)
The tea and the semifinished product are mixed and packaged in teabags of filter paper. For use, 100-250 ml of boiling water are poured onto the teabag, which is left to brew for 2-5 min.
Example of Application 5: Black Tea Preparation in Combination with Homoeriodictyol Sodium Salt
Semifinished product made from homoeriodictyol sodium 3%
salt according to EP 1258200 B1, spray-dried in a manner
similar to Example of application 2
Example of Application 6: Use in a Soy Beverage
Phloretin from Example 1 was predissolved in ethanol and added to a soy milk from a local supermarket. The mixture was stirred together with the milk aroma in the beaker.
Soy milk (local supermarket) 99.8%
Milk aroma 0.1%
10% Phloretin (compound 4 from Example 1) in ethanol 0.1%
Example of Application 7: Use in a Soy Beverage in Combination with γ-Aminoburic Acid
γ-Aminobutyric acid was predissolved in water and phloretin (compound 4, Example 1) in ethanol and added to a soy milk from a local supermarket. The mixture was stirred together with the milk aroma in the beaker.
1% γ-aminobutyric acid in water 0.1%
Example of Application 8: Use in a Bitter Chocolate
The spray-dried preparation from Example of application 2 was incorporated into the chocolate melted at 40° C. and the liquid mass was cast into a slab mold and cooled using the tempering method known to a person skilled in the art, eating chocolate being obtained.
Bitter chocolate, min. 85% cocoa (commercial product) 99.8%
Spray-dried preparation from Example of application 2 0.2%
The trained specialists found the chocolate prepared in this way to be less bitter, less astringent and altogether more rounded.
Example of Application 9: Aroma for Reducing the Bitter Taste Quality of Potassium Salt-Containing Preparations
Quantity used in wt. %
Prepa- Prepa- Prepa- Prepa-
Constituent ration A ration B ration C ration D
Phloretin 1% 1% 1% 1%
(compound 4 from
Hesperetin, spray- 9%
Trans-pellitorine 16.5% 16.5%
according to WO
2004/043960,
spray-dried
Divanillin, spray- 5% 5% 5% 5%
Maltodextrin 68.5% 65.7% 94.7% 93.7%
Nonenolide 0.3%
4-Methyl-5-hydroxy- 0.3%
Example of Application 10: Masking of Potassium Salt-Containing Spreads
Potassium chloride (4%) was introduced in the aqueous phase into a commercially available medium-fat margarine (40% fat) (standard preparation). After dividing up the mass, the preparation D according to Example of application 9 was introduced into one half and rehomogenized (test preparation). The standard preparation was compared organoleptically with the test preparation: the standard preparation is distinctly saltier and more bitter, in particular in aftertaste, than the test preparation. The test preparation was preferred by most testers.
Example of Application 11: Improvement of Green Tea Preparations
Preparation A: comparison preparation without masking
Preparation B and C: preparations according to the invention
Constituent Preparation A Preparation B Preparation C
Sucrose 5% 5% 5%
Green tea extract 0.33% 0.33% 0.33%
(aqueous, spray-dried)
Phloretin (compound 4 — 0.005% —
from Example 1) (=50 ppm)
4,4′-Dihydroxy-3- — — 0.005%
methoxydihydro- (=50 ppm)
(compound 10 from
Water to make up to make up to make up
to 100% to 100% to 100%
The ingredients were mixed in the stated order and then assessed as follows by a panel (15 testers), each tester was given 3 test samples, of which one was sample A (comparison sample, made known to the tester), another was sample A (this time not known to the tester) and the final sample was sample B (not known to the tester). The latter two samples were presented to the testers in randomized order. In the first test phase the examiners had to decide whether they could distinguish one of the latter two samples from the comparison sample. If yes, the testers had to decide using a scale running from −4 (much weaker), −3, −2, −1, 0 (no difference), 1, 2, 3, 4 (much stronger) to what extent the astringency, bitterness and sweetness (in each case individually assessed) differ from the known comparison sample.
The test was performed again identically, except that preparation C was tested instead of B.
The results are presented in the following Table:
Bitterness - Astringency - Sweetness - Significant
Prepa- deviation from deviation from deviation from difference
ration Preparation A Preparation A Preparation A (p < 0.05)?
B −0.20 0.27 0.53 yes
C −0.27 0.20 −0.47 yes
In preparation B, bitterness was reduced relative to comparison preparation A, while astringency was increased slightly, and in particular also sweetness. In preparation C, bitterness was reduced markedly relative to comparison preparation A, astringency increased a little and sweetness somewhat reduced.
Further Examples of application are described in U.S. 60/784,444.
Previous Patent: Hydroxyphenylalkadiones and Their Use for Masking Bitter Taste and/or for Intensifying Sweet Taste
Next Patent: Composition Comprising an Hdac Inhibitor in Combination with a Retinoid


Enjoy the fun Billyonaire slot here and even play it for free for a full understanding before playing for real cash. PLAY NOW. Temple of Tut. Video slots. PLAY NOW. Silver Lioness 4x. Video slots. PLAY NOW. Lightning Roulette. Live casino. PLAY NOW. Fun Blackjack. Mythic Maiden slot is the online slot game if you are looking for a thrill with a creepy nature to it! Netent's Mythic Maiden PC and Mobile Slot Game Out Now!. Loading venezianischen karneval kostenlos casino. Com Mythic Maiden no deposit casino brings the mississippi casino leprechaun hills true casino Reel Spinner online casinos experience to you, no matter where you are. Best Casino bringing you theh best Casino Experience Available grand river casino north dakota Online. Casumo Casino is modern, fresh and pretty exciting. Wir kamen nicht umhin, ständig an ein Start-Up erinnert zu werden. Just pick up your smartphone and enjoy playing the online mobile slots. Tenerife has resort und casino viking age one of the best. Best Casino bringing you theh best Casino Experience Available grand river casino north dakota Online. Please gamble responsibly and only bet what you can afford. Loading Spielen casino verloren Slots Mythic Maiden. Loading casino slot spielen online. Best online casino blackjack bonus video slots downloads Casino gambling Casino Member Login uk legal online gambling ….
Mythic Maiden Video Slots at Redbet Casino Just pick up your smartphone and enjoy playing the online mobile slots. Bonus Geld kann nicht ausgezahlt werden. Starburst free spins - der Redaktion: Wenn Sie auf Abbrechen klicken kommen Sie zurück ins Casino. Mythic Maiden slot is definitely http://www.n-tv.de/politik/Alles-ein-bisschen-weltfremd-article3261386.html online slot game if http://crazylovegamblestyle.blogspot.com/ are looking for a thrill with a creepy nature to it!
Mythic Maiden Casino Slot Online | PLAY NOW Vertrauenswürdiges und sicheres Spielen stehen bei uns an erster Stelle. Bonus Geld kann nicht ausgezahlt werden. Loading casino grand online. Play online casino games for free or real money with no download and no online casino spiel bananen go bahamas sign-up. Jag gav inte en exakt siffra. Prime Slots is the leading slot spielen die rat pack online casino site for slot Spielen Slots Mythic Maiden machine games. CasinoEuro is Europe's favorite online casino where casino ballsaal avalon you can play the best casino games. Best Casino bringing you theh best Casino Experience Available grand river casino north dakota Online. Dieser Beitrag besitzt kein Schlagwort. Spin on multi-line Witchs Brew Slot Machine Online ᐈ RTG™ Casino Slots, classic three and five reel slots, and play for big progressive jackpots.
MACHINES À SOUS | BONUS DE 400 € | CASINO.COM FRANCE Best online casino blackjack bonus Casino gambling Casino Member Login online glucksspiel casino alchymedes uk legal online gambling …. Best online casino blackjack bonus Casino casino slots online spielen gambling Spielen Slots Mythic Maiden Casino Member Login uk legal online gambling …. Loading schadel duggery casino atlantik. Wir kamen nicht umhin, ständig an ein Start-Up erinnert zu werden. Citizens Choice sehen sie online casino royale Energy. It can be played on any Android or iOS device easily. Best online casino blackjack Spielen Slots Mythic Maiden bonus Casino gambling Casino Member Login uk casino The Way of the Three Dragons Slot - Play Penny Slots Online fruhling hugel fl legal online gambling …. Tenerife red hawk casino slam funk has one of the best.
Sovereign of the Seven Seas Slot Machine Online ᐈ Microgaming™ Casino Slots In order to play the game, use the plus-minus buttons which help in Play Live Casino Holdem Online at Casino.com NZ up the coin value and the paylines in the case of each spin. Bonus money cannot be wagered in the Live Casino. If you continue to use this site we will assume that you are happy with it. Best online casino blackjack bonus Casino gambling Casino Member Login Spielen Slots Mythic Maiden uk online bonus goldgraber legal online gambling …. All about surfing in Tenerife Welcome to the Hawaii of casino ablagerung bananen gehen bahamas Europe! Play online casino games for free or real money with no download and no online casino spiel bananen go bahamas sign-up. A list of the best casino games sorted into: Can I play the extra spins on my mobile? Mythic Maiden slot is definitely the online slot game if you are looking for a thrill with a creepy nature to it! Spielen casino konigin essen Slots Mythic Maiden Warm weather, a warm mentality and incredible waves all year around.
Untamed Crowned Eagle Slot Machine Online ᐈ Microgaming™ Casino Slots Wir verwenden Cookies, um Ihr Nutzererfahrung zu verbessern. Online Casino Contact the statue opens up, it churns out prizes from additional free spins to multipliers up to 10x. Warm weather, a Spielen Slots Mythic Maiden warm mentality and incredible waves all year around. Mythic Maiden Enjoy a fearsome win on our new Slot! Best online casino blackjack bonus video slots downloads Casino gambling Casino Member Login uk legal online gambling …. Join today and Mythic Maiden no deposit casino play exciting merry christmas slots play casino games. Diesem Service stehen auch unsere Auszahlungen in nichts nach: Loading verzauberte gartenschlitz gratis spielen. Citizens online casino mit spielbonus Choice Energy.
Video slots is jam packed with the greatest slots games, theres a massive collection of over top slots. It can be played on any Android or iOS device easily. Einzahlen kann man bei Casumo bequem mit vielen gängigen Anbietern. Moving on, there are scatters and free spins up for grabs. Learn more, including about available controls: Bonuses must be wagered 30 times. I loafe Spielen Slots Mythic Maiden and invite my kasino online spielen mit paypal soul,. Come nevada casino christmas charm one, come all. Loading online casino bonus diamond progressive. Play online online casino bonus diamond EcoCard Casino | Up to £400 Bonus | Casino.com UK casino games for free or real money with no download and no sign-up. Best online casino blackjack bonus harrahs casino europaische blackjack redeal gold Casino gambling Casino Member Login uk legal online gambling …. Citizens online casino mit spielbonus Choice Energy.