JPS59106268A - Aspartame compositon enhanced in solubility - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel dipeptide sweetener compositions and methods for increasing the solubility of dipeptide sweeteners. In particular, the present invention relates to sweetener compositions comprising a mixture of a dipeptide sweetener and one or more solubilizers. The invention further relates to a method of increasing the solubility of dipeptide sweeteners in aqueous solutions.

Dipedetyl compounds, especially α-L aspartyl phenylalanine methyl ester (aspartame)
was found to have a strong sweet taste.

The manufacture and use of aspartame is covered by U.S. Patent No. 3.49.
No. 2,131, No. 5.642.491 and No. 3
, 780.189 will be described in the specification this winter. These patents are incorporated herein by reference.

Although these dibedecyl V have strong sweet taste, such dipeptides generally have limited solubility.

The rate of dissolution of Dipedeti V into aqueous solutions is significantly slower than that of sucrose. Although the problem of dissolution rate and solubility of dipedetyl is well documented, it remains largely unsurmounted. Attempts to increase the solubility of dipedetyl with various salts and metal complexes of dipedetyl have been sanctioned. ing.

U.S. Patent No. 4,029,701 describes that dipedetyl hydrochloride is more soluble in aqueous solution than the sweetener itself. Hydrohalides do not exhibit thermal stability. U.S. Pat. No. 4,153,757 discloses increased solubility of sodium and potassium salts of aspartame in gelycerin. High thermal stability and Sulfate and alkyl sulfonate salts of aspartame that exhibit rapid dissolution rates in aqueous media are disclosed in U.S. Application No. 06/383.393. The present invention relates to a dipeptide sweetener-metal complex.

US patent number! No. 1,761,288 for increasing the solubility of aspartame.

A method of spray drying aspartame is described. but.

All the above references disclose dipeptide sweeteners and their respective salts and metal complexes which are structurally characterized as mono-compounds or complexes.

The present invention relates to the formula: [wherein the stereochemical coordination is: DL-DL, DL-L, L-DL, or L-
and R is (a) alkyl having 1 to 6 carbon atoms.

(b) arylalkyl (the alkyl portion has 1 to 6 carbon atoms and the aryl portion has 6 to 10 carbon atoms); or (c) cycloalkyl has 3 to 7 carbon atoms.

and n is an integer from 0 to 5.

R1 is (a) alkyl having 1 to 6 carbon atoms, or (b
) a saturated, unsaturated or partially saturated 6 carbocycle, which may be optionally unsubstituted or substituted in the 4 position by R2, where R2 is (a) HyProxy;

(b) Alkoxy containing 1 to 6 carbon atoms.

(c) alkyl having 1 to 6 carbon atoms; (d)
Halogen, or (e) 5(0)((OH2)1.(OHM),(
where f is 0, 1 or 2 and k is an integer from 0 to 5 with the proviso that n is 1 or 2)] The agent is H2EiO4 or NaH8O4, K) TaO2, ? JH4) TaO2,C
a0%, MgC4.

A1.0rso4)*, Al (H80,)(80
,).

+614!2 (H804)4804, Mg
, (No. H80) 2so, .

Ca(H8O4)2, C! a2(H8O4)280
4.

Mg(H8O4)2, Zn(H8O4)2.

Zn2(H6O4)2804.

Fe(Tl)()T”0t)2 m Fe(m)(H
so4)3.

Fe(TT)2(aso, )2so, and Fe
(ITJ) (H8O4)S O4, and Fe(TrI
)z(aso4),so.

is a solubilizing salt selected from the group consisting of .

Two further aspects of the present invention relate to a method for producing a sweetened aqueous solution comprising adding the sweetener composition described above to an aqueous solution, or adding a dipeptide sweetener to an aqueous solution containing one or more of the solubilizers described above.

A preferred dipeptide sweetener is aspartame.

Preferred compositions of the invention include aspartame and KHS.
O3, Na) TaO2, Mg(H8O4)2, H2
It comprises a mixture of one or more solubilizers selected from the class consisting of SO4 and Ca(H8O4)2. A most preferred composition is aspartame and Na)T.
aO2 and/or 'FTEIO.

Examples of alkyl having 1 to 6 carbon atoms are methyl, ethyl, propyl, l-butyl, pentyl, hexyl and their isomers.

Examples of aryl moieties having 6 to 10 carbon atoms are phenyl, naphthyl and benzyl.

Examples of cycloalkyl having 3 to 7 carbon atoms are cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl and cycloheptyl.

Examples of alkoxy having 1 to 6 carbon atoms are methoxy, ethoxy, propoxy, butoxy, pentoxy and hexoxy and their isomers.

Examples of halogens are chlorine, bromine and fluorine.

Examples of aqueous systems are water and foods that contain water.

A preferred stoichiometric ratio of dipeptide sweetener and solubilizing salt ranges from about 2:1 to 1:2, most preferably from 1:1 to 1:2.

The compositions of the present invention are prepared by simply mixing the dipeptide sweetener with one or more solubilizing agents. When the solubilizing agent is a salt, the resulting composition comprises the dipeptide sweetener and the solubilizing agent. It is a physical mixture of chemical salts and there is no chemical interaction between the dipeptide sweetener and the solubilizing group.

In view of the fact that the compositions of the present invention are more than just physical mixtures of dipeptide sweeteners and solubilizing salts, the use of these compositions to prepare sweetening solutions is useful in the manufacture of dipeptide sweetener salts. Eliminate the time and expense associated with Additionally, the use of the compositions of the present invention allows the solubility of Dipepti V to be varied by simply using varying amounts of solubilizer.

Solutions containing the Dipedeti P sweetener can be prepared by dissolving a composition containing the dipeptide sweetener and a solubilizer in an aqueous solution, or by dissolving the Dipedeti P sweetener directly into an aqueous solution containing one or more solubilizers. It is prepared by squid. Gentle heating and/or stirring can be used to improve dissolution rates for concentrated solution preparations.

The compositions of the present invention have sweetening properties and can be formulated for a number of useful applications. For example, bags for the production of liquid sweeteners or sweetening solutions for consumer use.

Sachets or tablets can be manufactured. On an industrial scale, the compositions of the invention may be sold in bulk for use in concentrated sweetening solutions in restaurants, large scale food manufacturers and the like. Highly concentrated solutions containing sweetener compositions are liquid,
Can be used as a low calorie sweetener. These liquid, low-calorie sweeteners are used to facilitate processing in food products such as gelatin detates, fruit-flavored beverages, cereals, cake mixes, fruit juices, syrups, salad dressings, vet foods, and table sweeteners. There is.

It is important to note that the compositions of the invention are stable. Compositions of the present invention containing dibedecyl sweetener and salt can be stored dry and reconstituted at the time of use. However, it will be clear to those skilled in the art that its use is not limited to the systems shown here, but would find important application in pharmaceutical preparations such as tonics.

The invention will become more fully apparent from the following examples. These examples are illustrative only and are not to be construed as limiting the invention in spirit or clause, as many modifications, both to materials and methods, will be apparent to those skilled in the art from this disclosure. do not have.

Aspartame concentrations in the compositions or solutions prepared in the following examples are determined using high pressure liquid chromatography (HPLO) techniques. The degradation products of aspartame, f'', i.e., diketopiperazine and aspartyl phenylalanine, are measured simultaneously using the same 1-TPLO method. All concentrations are in weight percent unless otherwise specified. ``physical stability'' means the degree to which aspartame is dissolved in a solution, that is, aspartame does not precipitate at all in a physically stable solution.Example 1 of the description of preferred embodiments Composition of the present invention The following solution was prepared using: A composition containing a mixture of aspartame and one or more solubilizers was added to an appropriate amount of water, and the amount of aspartame dissolved in the water was measured. The results obtained are shown in the table below.

Example 2 455.1, f7 aspartame and 225.3
The stability of aspartame in a composition comprising a mixture of KH8O, Kl-TSO, and aspartame powder was determined by mixing aspartame and its decomposition products, diketopiperazine and aspartyl phenylalanine (present over a period of time). ) was measured. The results obtained are shown in the table below.

(V+#%) (Mold needle%) (Weight%) Zero time 65.9 0,31 0
．． 131 months (room temperature) 65.4
0.28 0.151 months (45°
C) 68.0 0.34
0.176 months (room temperature) 65.9
0.32 0.143 months (
45°G) 68.2 0.39
0.15 Example 3 A concentrated aspartame-solubilizer solution with a stoichiometric ratio of 1:1.05 (aspartame:solubilizer) was prepared and stored at room temperature. aspartame in each solution,
The concentrations of diketopiperazine and aspartyl phenylalanine were measured during the period and the results obtained are shown in the table below.

Example 4 The solubilizer was first dissolved in water and then the aspartame was added to the resulting solution. The physical stability of the obtained solution was observed and estimated, and the obtained results are shown in the table below.

Example 5 Effect of soluble agent concentration on aspartame solubility.

Various amounts of xnso, (0-5 g) were dissolved in 50 ml of distilled water. 1 (L?) of aspartame was added to each solution and the resulting solution was stirred for 40 minutes. The solution was filtered and the aspartame concentration in the filtrate was measured using high pressure liquid chromatography technique. Shown in the table below.

1 0 ~ 1 2 1.0 4.93
2.0 B, 14 3.0
9.5 Example 6 Concentrated table sweetener.

3.8 g aspartame and 1.4 g KH8 in 100 m/plastic jar marked at 20 WIA intervals
O.

A composition containing the following was added. The bottle is fitted with a dropper cap and/or a spray cap. About 20 to about 801r in the composition
LILf) Warm water is added and the resulting solution can be used as a table concentrate liquid sweetener for two consecutive days. Liquid sweeteners use dripping caps for coffee and other beverages;
Fruits and other solid foods can be added using a squirt cap.

Agent Asamura Hao

Claims (1)

[Claims] (1) Aspartame and NaH8O4, KHSO3, NH4H8O4, CaC4
, MgCJ2+. Af(H8O,)3. M(H3O,)(So4),
Af2(H8O,), So4゜Ca(H9O4), 2
, 0a2(H3O4)2SO4. Mg2(H8O4)2SO4, Mg(I(804)2
, Zn(H8O4)2rZn2(H8O4)2sO4
+Fe(II)(Hsot)21F8(IIT)(H
8O4)3. Fe(II)2(Hso,)2so4°Fe(m)(Hso+)so4. and F e air
) 2 < HsO4)4S O4. The aspartame and solubilizer in this mixture is approximately 10=
It is characterized by a stoichiometric ratio of 1 to about 1=20. Dipeptide sweetener composition. (2) The solubilizer is Mg(H804)2. A composition according to claim 1. (3) The solubilizer is NaH804. A composition according to claim 1. (4) The composition of claim 1, wherein the solubilizer is KT(So). (5) The stoichiometric ratio of aspartame:solubilizer is about 1=2 to about 1=1. The composition according to claim 1, 2, 3 or 4. (6) Aspartame and NaH8O4, KTJSO4', NH4H804,'
CaC4, MgCJ2゜Af(H8O4)3,
Af (H604) (So,), A+! , (H8
O, ), So,. (!a(H8O4)21 Ca2(H804)2804
+'Mg2(H3O+)psoz+Mp(H8O4)
2, Zn()TaO2)2*Zn2(H8O4
)2804. H2BO3, Fe(TI') (Hso, )2. Fe(
III) (uso,),,. Fe(1)2(Hsot)2S04, Fe(m)
(Hso, )so, and Fe(m)2(aso,
), so. adding to the aqueous solution a composition comprising a mixture of solubilizers selected from the group consisting of aspartame:solubilizer in a stoichiometric ratio ranging from about 10:1 to about 1:20. . A method for producing a sweetened aqueous medium. (Ca) Aspartame, Na)TaO2, KT(804, NH4H8O4, Ca
C,12,MgCJ2゜A,e (,TTSO4)F
, M (Hso,) (so,), Shima (Ilso,
,),so,. 0a(TTSO4)z + Ca, (H8O4)+S
O4+ MF2(H8O+)2so4+Mj'(""0
4)2 + Zn()TE01)2 + Zn2
(TTSO4)2S041H2SO4, Fe(TI)(
) TE01. )2, Fe(m)(H8O4)*
. Fe(1'))2()TE01)2804 *Fe(
IIT)(H8O4)SO41 and Fe(m)2(H
8O4) 4804 + in an aqueous solution in which a solubilizer selected from the group consisting of
It is characterized in that it is added in a stoichiometric ratio of =1 to about 1=20. Method for preparing sweetened aqueous medium. (8) Solubilizers are NaH8O4, KTTSO4, )T2
SO4 or Mg(H8O4)p. The method according to claim 7. (9) The solubilizer is 1'Jal (804, KHSO3 or ug(Hso, )2. The method according to claim 8. The stoichiometric ratio of Ul aspartame: solubilizer is about 1 :2 to about 1:1. Claims 7 and 8
or the method described in paragraph 9.