WO2001089994A1

WO2001089994A1 - Method of preparation of an antiperspirant salt

Info

Publication number: WO2001089994A1
Application number: PCT/EP2001/004765
Authority: WO
Inventors: Alexander Thomas Ashcroft; Johannes Breker; Keith Gosling; Bruno Kaufmann
Original assignee: Unilever Plc; Unilever N.V.; Hindustan Lever Limited; Bk Giulini Chemie Gmbh & Copmany Ohg; Smith, Philippa, Margaret
Priority date: 2000-05-19
Filing date: 2001-04-27
Publication date: 2001-11-29
Also published as: GB0012266D0; AU6223901A

Abstract

A method of manufacturing a polymeric aluminium chlorhydrate having the empirical formula: A12(OH)6-axa?YH2 wherein X is Cl, Br or I, a is 0.8 to 1.33 and Y is 0.19-1.4, comprising heating an aqueous solution of the aluminium halohydrate with a solution containing an acidic source of halide ions at a temperature of between 80°C and 130°C for a time period of 50 minutes to 10 days, such that the Al/X ratio in the resulting polymer is between 1.5:1 and 2.0:1, and such that the aluminium concentration in the resulting solution is between 0.5 and 3.8wt%, and drying the resultant material to provide a salt having a water content of less than 12wt%.

Description

Method of Preparation of an Antiperspirant Salt

This invention relates to a method of preparation of basic aluminium antiperspirant salts having enhanced activity, and to the resulting salts.

It is known to heat basic solutions of aluminium salts, such as salts having a general formula of Al₂ (OH) ₆-X_a. where X is a halogen and preferably chlorine, and a is between about 0.5. and 5 but preferably between about 0.9 and 1.5, so as to modify the salt in such a way that its efficacy as an antiperspirant active is increased. Representative of such prior processes is US 4,359,456 (Gosling et al) which describes an improved antiperspirant of empirical formula Al₂ (OH) ₆-_aX_a which has a Band III aluminium value as defined therein of at least 20%.

In this teaching, aluminium chlorhydrate of varying types, having various Al/Cl molar ratios, and concentrations of aluminium of 2.5-8.5%, are typically heated at temperatures ranging from 97-120^ΞC for periods of time ranging from one hour to 48 hours in closed reactors, in order, to provide the activated aluminium active. A number of the compositions prepared in this patent were also dried and isolated.

Whilst the activated aluminium chlorhydrate (AACH) compounds made by prior methods have produced antiperspirant actives which have a generally relatively high efficacy in topical products, it is desirable that antiperspirant actives be made if possible of a higher efficacy. This is because topical products made utilising such actives can be made to have a higher efficacy than other commercially available products, thereby minimising the frequency and/or the intensity of axillary wetness events witnessed by users.

A higher efficacy antiperspirant active is also desirable because it provides the opportunity to formulate products either of intermediate efficacy, or of an efficacy akin to that of currently available top efficacy commercial products, but in any event utilising a lesser amount of active in the topical product than is currently used. Such opportunities may provide for a possible cost reduction in the manufacture of the product, or reduced irritation in the topical product, since the concentration of the active material present is less than that in currently available commercial products. In addition, if the topical product contains a lesser amount of active, it may be easier to formulate, which in itself provides benefits.

As an associated aspect, we have found that a problem with antiperspirant actives for use in topical applications is that it is possible for their efficacy to decrease over a period of time. This clearly can present problems to the manu acturer, since it means not only that once an active salt has been made that it must be must be quickly used and formulated, but also that there is possibility that topical products manufactured with such salts may also find their efficacy decreasing over a period of time.

We have surprisingly found after much experimental investigation that by selection of appropriate processing parameters, it is possible to provide an improved process for activation of aluminium chlorhydrate. The resulting antiperspirant novel actives have an efficacy which is typically at least equivalent to that provided by current activation methods, and may also be more stable than prior actives, providing sustained efficacy over a period of time.

Thus, according to a first aspect of the invention, there is provided a method of manufacturing a polymeric aluminium chlorhydrate having the empirical formula

Al₂(OH)6-aXa.YH₂0

wherein X is Cl, Br or I, a is 0.8 to 1.33 and Y represents an associated amount of water and is typically between 1.5- 2.5, comprising heating an aqueous solution of the aluminium halohydrate with a solution containing an acidic source of halide ions at a temperature of between 80²C and 130²C for a time period of 50 minutes to 10 days, such that the Al/X ratio in the resulting polymer is between 1.5:1 and 2.0:1, and such that the aluminium concentration in the resulting solution is between 0.5 and 3.8wt%, and drying the resultant material to provide a salt having a water content of less than 12wt% .

In a highly preferred embodiment, the above method of manufacture also constitutes a method of improving the antiperspirant efficacy of the aluminium chlorhydrate salt, and/or a method of improving the stability of the aluminium chlorhydrate salt .

Preferably, the halide ion is chloride. Conveniently, the acidic source of chloride ions is aluminium chloride hexahydrate or hydrochloric acid; hydrochloric acid is a preferred source. In certain preferred embodiments, a is between 0.9 and 1.2, more preferably between 1.0 and 1.15, and is most preferably

1.1.

Conveniently, Y is between 1.5 and 2.5, and is most preferably between 1.7 and 2.3. In relation to the water content of the salts, the most convenient way of assessing this is with a moisture balance. It will however be appreciated that the values for water content given by this method do not bear a direct relationship to the values quoted in the empirical formula which are derived from elemental analyses. Measurements by moisture balance do however represent a practical and reproducible measure that relates to the activity and stability characteristics of the salts.

It has also been found that the optimum concentration of aluminium polymers in the resulting solution is a function of the temperature at which the heating step is carried out, which heating has the effect of ageing the composition. Thus, for example, if the ageing step is carried out at 100°C, then it is preferable that the aluminium concentration in the resulting solution is in the range 1.7-2.1wt% by weight of aluminium, more preferably between 1.75 and 2.05 wt% . Where the ageing step is carried out at 120°C, it is preferable that the ageing step is carried out at an aluminium concentration of 2.3-2.7%, more preferably between 2.4 and 2.6 wt%, and most preferably 2.5%. Where the ageing step is carried out at 130°C, it is preferable that the ageing step is carried out at an aluminium concentration of 3.2 - 3.8%, more preferably between 3.4 and 3.6 wt%, and most preferably 3.5%. In operating the process according to the invention, the initial concentrations of aluminium containing compounds are calculated to provide the desired final aluminium concentrations. In certain embodiments, the preferred ageing temperature is in the range 100-110°C.

Conversely, the preferred ageing period is also dependent on the temperature at which the ageing step is conducted. For example, if the ageing step is carried out at 80°C, the ageing step may last for a period of up to 10 days, most preferably 6-8 days. If the ageing step is carried out at 100°C, preferably the ageing step is carried out for a period of 10 to 48 hours, more preferably 20 to 30 hours. If the ageing step is carried out at 120°C, the ageing step is preferably carried out for a period of 2 to 10 hours, more preferably 3 to 5 hours. If the ageing step is carried out at 130°C, the ageing step is preferably carried out for a period of 50 minutes to 100 minutes, more preferably 70 to 80 minutes.

In order to increase the overall rate at which the desired antiperspirant active is generated, it is preferable to perform the ageing step by sequential use of a high temperature followed a lower temperature. This procedure can also lead to a particularly desirable mixture of aluminium species and correspondingly good antiperspirancy performance for the salt produced. The procedure can beneficially be done using a higher concentration of aluminium in the high temperature ageing step than in the lower temperature ageing step. In a preferred procedure, the ageing step is performed at 110-130°C for 0.5 to 10 hours, followed by a subsequent ageing step at 85-100°C for 3 to 48 hours. It is generally found that the use of temperatures towards the top of these ranges enables good products to be formed after ageing times towards the bottom of the ranges indicated and vice-versa . It is further preferred that the aluminium concentration for the 110-130°C stage is 2.5 to 3.5% by weight and that the aluminium concentration preferred for the 85-100°C stage is 0.8 to 2.5% by weigh .

Preferred aluminium solutions and salts according to the invention have a relatively low concentration of Al_i3 species, as detected by ²⁷Al NMR techniques, which species tend to be present in aluminium salts and solutions which have not been subjected to the appropriate ageing conditions. Conveniently, Alι₃ species are present in aged solutions produced according to the invention at levels of less than 20wt%, more preferably less than 10wt%, and often less than 7% by weight of the aluminium species.

We have also surprisingly found, somewhat contrary to certain prior art teachings, that small amounts of Band 0 polymers may be present in preferred salts and solutions made according to the invention. These Band 0 polymers, which are thought to be inactive as regards antiperspirant activity, and which have an effective diameter of 100 Angstroms or greater, may account for less than 10wt%, more preferably less than 5wt%, and often levels less than 2.0wt% by weight of the aluminium species. In preferred salts and solutions they are often present at levels representing at least 0.1% by weight of the aluminium species. It is the presence of Band 0 polymers that accounts for cloudiness often observed in the solution in many of the prior art methods.

For the avoidance of doubt, it should be noted that in this specification, unless otherwise specified, quoted amounts of the various individual aluminium polymer species in the composition are expressed as percentages by weight of the aluminium polymers, and refer to the total aluminium species in the composition, including polymers in the so-called Band 0 range .

Preferably, the ratio of Al/X in the final reaction solution (i.e. after the ageing step has been carried out) is 1.7 or more, and it also may preferably be 1.9 or less. More preferably it may be 1.75:1 or more, and may also be 1.85:1 or less, and most preferably is 1.8:1. All the Al/X ratios referred to in this specification are atomic ratios.

Conveniently, the water content in the resulting (dried) antiperspirant active salt is no lower than about 2%, is preferably at least about 4%, is more preferably at least 6%, and is even more preferably at least 8% by weight of the composition. Preferably the water content of the dried salt is less than 12%, and is often less than 10% by weight of the salt. It has been found that reducing the water content of the salt is desirable for the long term stability of the salt, as reflected by its antiperspirant efficacy. These preferences are particularly relevant to antiperspirant active salts dried by spray drying.

With regard to the minimum water content, it is thought that whilst too little water is not in itself harmful to the stability of the salt as such, the drying regimes to which the salt needs to be subjected to get the water content to particularly low levels may be deleterious to the more active polymer species in the salt. Water contents quoted in this application are measured using a Sartorius MA30 moisture balance, on an "auto" programme with a set point of 100°C. Samples were stored in sealed vessels, introduced onto the balance at room temperature, and the temperature ramping programme started immediately. Quoted water content levels were based on an average value from a minimum of three repetitions .

Dried activated aluminium actives according to the invention can conveniently be isolated on an industrial scale by freeze drying or spray drying. Freeze drying is generally considered to be a less harsh drying technique, and hence may be considered to be a preferred drying method in certain circumstances, though spray drying may be considered to be a preferred technique in other circumstances, since it tends to result in a dried salt with a more consistent and desirable particle size distribution. This may therefore negate the need for further processing of the salt, such as for example by milling, to provide the desired particle size distribution. Where spray drying is used as the drying method, it is preferred that the dried powder is cooled as soon as possible after the drying step, for example by conveying it from the drying stage to the next stage (e.g. a storage stage) in a cooled, low humidity current of air.

The combination of processing parameters described has been found to result in an activated salt which is preferred, and which provides a particularly high degree of antiperspirant efficacy when incorporated into a topical composition.

In a further aspect, the invention also provides an antiperspirant active salt made according to the process of the invention. Preferably, the heating (i.e. ageing) process is carried out at temperatures of 90²C or higher, and as described in US 4,359,456 (the content of which is incorporated herein by reference) , the heating is conveniently carried out in a sealed vessel at elevated pressure. As is widely appreciated, increasing the temperature of a chemical reaction typically causes it to proceed faster, which is desirable from an economic stand point. However, at temperatures above 120^SC, there is a higher tendency for antiperspirant inactive species of salt to form, and in any event, it has been found that the absolute amount of antiperspirant active species which can be formed is actually higher when the ageing step is carried out at temperatures closer to 100°C, for example 90-105°C.

Preferred heating regimes include where the temperature is around 95-105²C, heating the reaction mixture for around 16 hours to 2 days, preferably around 24-30 hours; and where the reaction temperature is around 115-125²C, heating the reaction for a period of around 2-10 hours, preferably for about 3 to 5 hours at 120°C.

The above range of processing parameters has been found to provide a superior activation process for aluminium chlorhydrate compositions according to the invention, providing antiperspirant actives of superior efficacy.

In accordance with a further aspect of the invention there is provided a topical antiperspirant or deodorant composition comprising an effective amount of an activated aluminium chlorhydrate salt prepared in accordance with the process described above. Compositions which utilise aluminium salts produced according to the invention may be any of the topically applied forms, including sticks, roll-on lotions, aerosols, creams and soft solids, and pump spray formulations. Topical compositions according to the invention are preferably anhydrous; that is, the composition vehicle (i.e. the components of the composition, excluding the antiperspirant active salt itself) contain less than about 2%, more preferably less than 1% by weight of water. It is also preferred that topical compositions deliver the antiperspirant active as a suspended solid, and not as a solution, though topical compositions containing antiperspirant active solutions are contemplated.

Although not limited as such, the aluminium salts formed according to the invention may have particular utility in propellant driven aerosol compositions, in which zirconium based actives, currently the most efficacious available, are prohibited in certain countries. Topical compositions containing actives made according to the invention may be formulated using those cosmetic ingredients which are used in the formulation of the particular topical composition, depending on the product form.

Conveniently, actives formed by the process according to the invention have a relatively high proportion of polymers contained in Band III compared to those in Band II of the Standard Basic Aluminium Chloride Solution Size Exclusion Chromatogram of the Size Exclusion Chromatography Test, as described in US 4,359,456. Preferably, the ratio of Band III to Band II material is greater than about 3:1. Conveniently the level of Band III material is more than about 55% by weight, preferably more than 65% by weight, of the aluminium polymer species. Conveniently, the amount of Band II material is less than about 30% by weight of the polymer species, more preferably less than 25% by weight of the polymer species .

Characterisation of materials containing species differing in size by means of size exclusion chromatography (SEC) is generally known. Two size exclusion chromatographic procedures are required for the complete characterisation of the basic aluminium compounds of this invention. Method 1 permits the characterisation of materials on the basis of the percentage of aluminium in species greater than 100 Angstroms in size. Method 2 leads to a characterisation on the basis of the percentage of aluminium in species less than 100 Angstroms in size. The two methods will now be described.

Chromatographic Method 1

For the determination of the percentage of aluminium in polymeric species having a size greater than 100 Angstroms (i.e. Band 0 material), a 30 cm by 7.5 mm internal diameter stainless steel column was used. This was packed with a porous silica, available commercially as Porasil from Waters Corporation. The silica was characterised as having a particle size range of 37 to 55 micrometers, an average pore size of 125 Angstroms, a pore volume of 1.0 cc/g and a surface area of 320 m²/g.

The column was packed using a dry packing technique together with lateral tapping as described in "Silica Gel and Bonded Phases, Their Production, Properties and Use in LC", by R P W Scott, Published by John Wiley and Sons, 1993, page 58. Following packing, the eluent, consisting of an aqueous solution of 0.1 molar sodium nitrate and 0.01 molar nitric acid in deionized water, was first introduced from the bottom of the column at a flow rate of 1.0 ml/minute and passage continued until the exiting eluent was free from air bubbles . The eluent flow was then rearranged to feed to the top of the column and the column incorporated into a system comprising the sequence: sample loop injector, column, and refractive index detector (e.g. Waters R410) . The detector was linked to an integrator that was used to monitor the separated fractions as they were eluted from the column. A standard eluent flow rate of 1.0 ml/minute was established.

In order that the column may be conditioned effectively and also to provide a standard material to qualify the performance of the column, a standard basic aluminium chloride was required. This was prepared by taking a sample of a 50% by weight aluminium chlorhydrate solution, available commercially as Aloxicoll-L from BK Giulini Chemie GmbH and Company OHG and characterised as having an aluminium to chlorine molar ratio of 2.01. This was diluted with deionized water to provide a 10.0% by weight aluminium chlorhydrate solution, and heated in a closed vessel at 100°C for 42 hours. The solution was spray dried to give the Standard Basic Aluminium Chloride Powder.

The column was conditioned by injecting successive 500 microlitre samples, prepared from the Standard Basic Aluminium Chloride Powder and deionized water to contain 1.25% by weight aluminium, until a constant chromatogram was achieved. A 200 microlitre sample, prepared from the Standard Basic Aluminium Chloride Powder and deionized water to contain 1.25% by weight aluminium, was then injected and two fractions corresponding to the bands in the chromatogram were collected and analysed for aluminium by plasma emission spectroscopy. The percentage of the total aluminium which appeared in the fraction eluted at the void volume (sometimes called the exclusion volume) of the column was 13.0% by weight and was considered as that deriving from polymeric material of a size greater than 100 Angstroms in effective diameter. Complete elution of all the aluminium in a sample applied to the column was checked by direct analysis of another sample of the same volume.

To prepare test solutions of materials for analysis for their Band 0 content, those already in solution were used undiluted unless the aluminium concentration exceeded 1.25% by weight, in which case they were diluted with deionized water to provide a solution containing 1.25% by weight aluminium. Solid materials (e.g. spray dried powders) were dissolved in deionized water to give solutions containing 1.25% by weight aluminium. These solutions were treated in an ultrasonic bath (e.g. Camlab Transsonic T660/H) for 2 minutes before application to the column.

Chromatographic Method 2

The analytical procedure used to determine the percentage of aluminium in species having a size less than 100 Angstroms (i.e. material in Bands I, II, III, and IV) was performed using a stainless steel column of dimensions 30 cm long and 7.0 mm internal diameter. This was packed with spherical porous silica of nominal particle size 5 micrometers diameter, an average pore size of 50 Angstroms diameter, a pore volume of 0.8 cc/g and a surface area of 450 m²/g. A suitable silica was that available commercially as Nucleosil 50 from Macherey-Nagel GmbH.

Although the columns used in the actual method employed by the Applicants were obtained ready packed from Jones Chromatography Limited of Hengoed, Mid-Glamorgan, Wales, if it were necessary to pack a column with the silica it could conveniently be carried out by the high-pressure slurry method (see "Silica Gel and Bonded Phases, Their Production, Properties and Use in LC", by R P W Scott, Published by John Wiley and Sons, 1993, page 60) using hexane as the packing medium. In all cases the column would be equipped at the bottom with a zero dead volume fitting containing a 2 micrometer porosity stainless steel support and after packing would be capped with another zero dead volume fitting containing a 2 micrometer stainless steel frit.

The packed column was connected into a chromatographic system consisting of an automatic sampler, high-pressure pump, column, and a differential refractive index detector to monitor sample fractions as they were eluted. The refractive index detector was linked to an integrator to provide a real-time chromatogram and a data system that was programmed to calculate the relative chromatographic band areas of the fractions as a function of their elution times. The system was instructed to measure the areas of bands not resolved to the baseline by dropping perpendiculars from the lowest point of the valleys separating the bands to the baseline. Newly packed columns were eluted with 200 ml of methanol at a flow rate of about 10 ml/minute, using a high pressure pump, to consolidate the bed and wash out the packing medium. This was followed by a change of eluent to the medium to be used for the analytical separations, in this case an aqueous solution containing 0.1 molar sodium nitrate and 0.01 molar nitric acid, and elution continued at a rate of 0.5 ml/minute until a flat base-line was achieved.

To provide a sample for conditioning the column and to act as a calibration standard a Standard Basic Aluminium Chloride Solution was prepared. This was carried out by dissolving 52.1 g of aluminium powder (99.97% aluminium by weight, grade 20/D supplied by The Aluminium Powder Company Limited of Holyhead, Anglesey, North Wales) and 93.2 g of aluminium chloride hexahydrate (supplied by Sigma-Aldrich Company Limited of Gillingham, Dorset SP8 4XT, UK) in 354.7 g of deionized water at about 90°C in a stirred vessel equipped with a reflux condenser. When all of the aluminium had dissolved the solution was filtered to remove traces of insoluble impurities and allowed to cool to room temperature. This gave a Standard Basic Aluminium Chloride Solution that contained 12.5% aluminium by weight and 0% as polymers greater than 100 Angstroms in effective diameter (i.e. Band 0) .

The column was conditioned by the application of multiple injections of 10 microlitre samples of the Standard Basic Aluminium Chloride Solution, diluted to 2.5% aluminium by weight, until a constant chromatogram was obtained from successive injections. To prepare test solutions of materials for analysis for their Band I, II, III, and IV contents, those already in solution were used undiluted unless the aluminium concentration exceeded 2.5% by weight aluminium, in which case they were diluted with deionized water to provide a solution containing 2.5% by weight aluminium. Solid materials were dissolved in deionized water to give solutions containing 2.5% by weight aluminium. These solutions were treated in an ultrasonic bath for two minutes then filtered through 0.2 micrometer porosity cellulose acetate filter units. The preparation of the test solutions was carried out within 10 minutes of their application to the column. Sample solutions were applied to the top of the column as 1 microlitre injections and eluted at a rate of 0.5 ml/minute.

When a sample of Standard Basic Aluminium Chloride Solution was diluted to 2.5% aluminium by weight and applied to the column four main bands were obtained. They were characterised by means of the ratio of the retention times of the principal peak in each band to the retention time of the peak due to the totally included species (in the case of basic aluminium chlorides the totally included species arise from the presence of hydrochloric acid. This can be shown by comparison of its retention time with that of a sample of 0.01 molar hydrochloric acid.) and their chromatographic band areas expressed as percentages of the total chromatographic band area representing aluminium-containing material:

Comparison of the total aluminium content of the eluted fractions representing Bands I to IV with that of another sample of the same volume that had not passed through the column showed that there was complete elution of aluminium species from the column. In a further experiment it was found that the relative aluminium contents of the separated fractions, expressed as percentages of the total aluminium contents of Bands I to IV, agreed closely with the relative area percents determined by integration of the signals from the refractive index detector for the same bands .

It will be appreciated by those skilled in the art that mechanisms of separation other than the principal mechanism of size exclusion may play a part in this type of chromatography. Examples of the processes would be adsorption effects and hydrodynamic effects. Thus although it is possible for a given column and constant operating conditions to lead to invariable relative retention times, minor variations in particle size range and pore size distribution of the packing materials may lead to slight differences in relative retention times and the splitting of the main bands. In our experience with standard columns packed with different batches of the specified packing material, the four aluminium-containing bands consistently fall within the ranges indicated:

Quantitatively, the amount of aluminium in the various Bands expressed as a percentage of the total aluminium of the compound under test is given by:

% Aluminium, Band 0 =

The percentage of aluminium in the fraction eluting at the column void volume according to Chromatographic Method 1

% Aluminium, Bands I, II, III, or IV =

Area of band corresponding to Band I, II, III, or IV fraction

(100-A) X

Sum of the areas of the bands corresponding to Bands I, II, III, and IV

where A is the percentage of the total aluminium which is contained in polymers greater than 100 Angstroms and is determined by Chromatographic Method 1.

Compositions according to the invention may also be characterized by the presence of certain spectroscopic peaks, as determined by ²⁷Al solution NMR spectroscopy. In the method of the invention, the aluminium polymers formed may be analysed by NMR techniques to show the presence of, and to quantify, different polymer species, which have characteristic peaks in the ²⁷A1 NMR spectrum. An example of these is the peak at 62.5 ppm downfield from the resonance of [Al (H₂0) ₆] ³⁺ • This peak has been attributed to the presence of a tetrahedrally coordinated aluminium atom at the centre of the complex ion [Al_i30 (OH) (H₂0) χ₂] ⁷⁺ by Akitt et al. (J.C.S. Dalton Transactions 1972 p604) , the structure of which was first established by G Johansson

(Acta. Chem. Scand. 1960 Vol 14 p771) . This ion has been subsequently referred to as the Alι₃0n ion by Schonherr et al (Zeitschrift fur Anorganische und Allgemeine Chemie, 502, 113-122 (1983)). The desired level of this ion in the aluminium salts of the invention is detailed earlier in the specification.

A set of broader peaks which are detectable at between 64 and 76 ppm downfield from [Al(H0)₆_³⁺ correspond to the AlPi, AlP₂, and A1P₃ polymer species referred to by Fu and Nazar in the above referenced paper. For the purposes of the analyses described herein, these peaks are grouped together and referred to as representing AlP_x species . The desired level of these species represents at least 40%, in particular at least 45%, and especially at least 50% by weight of the aluminium present .

For the quantitative determination of the percentage attributable to the various peaks, it is recommended that an external calibration standard having a resonance position outside the range of the spectrum under investigation be used. A suitable standard and method of use is aqueoussodium aluminate solution (concentration 0.1M, resonance position δ = 80 ppm) , contained in a sealed 5 mm NMR tube held concentrically inside a 10 mm NMR tube; the annular space between the two tubes being filled with analyte solution, and the aluminate standard being freshly made up and calibrated for each series of experiments . This latter calibration can be performed using an aqueous solution containing a known concentration (eg 0.02M) of an aluminium salt, such as aluminium nitrate (resonance position δ = 0 ppm) , as a primary standard. In the calibration procedure, the primary standard is placed in the annular space between the two NMR tubes . From the ²⁷A1 NMR spectrum of this system, the effective concentration of aluminium in the tube containing the external standard is calculated according to the equation:

where :

M_s is the effective molar concentration of aluminium in the external standard solution;

M_A is the molar concentration of aluminium in the primary standard solution;

I_s is the area of the peak corresponding to the external standard (at δ = 80 ppm for sodium aluminate) ; and I_A is the area of the peak corresponding to the primary standard (at δ = 0 ppm for aluminium nitrate) .

Thus M_s is the 'calibration factor' of the sealed tube of the external standard, and the use of this tube, as indicated above, with subsequent analyte solutions of unknown composition allows the amount of aluminium associated with particular peaks in the spectrum resulting from the analyte solution to be quantified.

In our experiments, all NMR measurements were carried out at room temperature using a Bruker Avance DRX 500 spectrometer with a probe free from the background aluminium signal. Sample tubes were made from quartz (also free from background aluminium signal) . The aluminium concentration of the analyte solutions whose polymer species were to be determined was in the range 0.3M to 1.0M. Spectra were obtained within 10 minutes of preparing the analyte solutions. The concentration of Alι₃0₄o ions present was quantified using the area of their peak at 62.5 ppm, together with an appropriate scale factor. The concentration of AlP_x ions present was quantified using the area of their peaks between 64 and 76 ppm, together with the scale factor used for the Alι₃0n ion.

The invention will now be further illustrated by way of the following non-limiting examples.

Examples 1-3

The object of Examples 1-3 is to demonstrate the effect of the aluminium concentration on the formation of the optimum antiperspirant active salts (Example 1) , and the effect of the Al/X ratio on the formation of the optimum antiperspirant active salts at different temperatures (Examples 2 and 3) .

A1C1₃.6H₂0 (99% purity, ex. Aldrich) was dissolved in 250 g distilled water in a round bottomed flask, along with Aloxicoll-L solution (BK Giulini Chemie, a 50% aqueous solution of aluminium cholorohydrate having a ratio of Al:Cl of 2.01:1.0), and a reflux condenser was added. The exact amounts of aluminium chloride and aluminium chlorhydrate required were calculated such that the required ratios of Al/Cl would be present in the resulting solution, and also such that the aluminium concentration in the resulting solution would be that required. In Examples 1-3, the amounts were varied to demonstrate the effect of carrying out the process at Al concentrations between 1.50-2.75% at constant temperature, (Example 1) , and to demonstrate the optimum A1:X ratio at temperatures of 100°C and 120°C (Examples 2 and 3) . As an alternative to Aloxicoll-L, Aloxicoll PF40 (ex. BK Giulini Chemie, a dry aluminium chlorhydrate powder having an Al:Cl ratio of 2.01:1.0) could be used.

For Example 1, the mixture was heated and stirred at 100°C for 24 hours, with the Al:X ratio being 1.8:1.0. For Example 2, the mixture was heated and stirred at 100°C for 24 hours, with the Al:X ratio being varied as described, and the aluminium concentration being kept constant at 2.5%. For Example 3, the mixture was heated and stirred at 120°C for 4 hours, with the Al:X ratio being varied as described, and the aluminium concentration being kept constant at 2.5%. With Example 3, the appropriate high pressure autoclave was used to allow the solution to be heated to a temperature of 120°C without water loss.

After the heating steps, the solution was cooled, and freeze dried or spray dried to provide a white/pale yellow powder. Samples were analyzed by SEC and ²⁷Al NMR, as described above . Results

Example 1

The results indicate that, based on the amount of Band III material and also the amount of AlP_x species present, that the preferred aluminium concentration at an ageing temperature of 100°C is at or close to 2.0%.

Example 2

The results indicate that, based on the amount of Band III material and also the amount of A1P_X species present, that the preferred aluminium to chloride ratio at a temperature of 100°C is at or close to 1.8:1.

Example 3

The results indicate that, based on the amount of Band III material and also the amount of AlP_x species present, that the preferred aluminium to chloride ratio at a temperature of 120°C is at or close to 1.8:1.0.

Example 4

This Example illustrates the optimum concentration of aluminium in relation to an ageing step carried out at 120°C for a period of 4 hours.

The ageing process was carried out in a similar manner to that disclosed in Example 1, except that the aluminium concentration was varied between 1.25% and 3.00% by weight, with the Al:Cl ratio being kept constant at 1.8:1. The resulting salts were spray dried. Results

The results indicate that at the ageing temperature and A1:C1 ratio chosen, the preferred aluminium concentration is at or close to 2.5%.

Example 5

This Example illustrates the optimum ageing time in relation to an ageing step carried out at 120°C, with the aluminium concentration being kept constant at 2.5%.

The ageing process was carried out in a similar manner to that described in Example 1, except that the reaction time was varied between 1 and 6 hours, with the Al:Cl ratio being kept constant at 1.7:1. The resulting salts were spray dried. Results

The result indicate that at the ageing temperature chosen, the optimum ageing time is approximately between 4 and 5 hours .

Example 6

This Example illustrates the optimum ageing time in relation to an ageing step carried out at 100°C, with the aluminium concentration being kept constant at 1.75%.

The ageing process was carried out in a similar manner to that disclosed in Example 1, except that the reaction time was varied between 5 and 66 hours, with the Al:Cl ratio being kept constant at 1.8:1. The resulting salts were spray dried. Results

The result indicate that at the ageing temperature chosen, and the given ratio of A1:C1, the optimum ageing time is approximately between about 18 and 22.7 hours.

Example 7

This Example illustrates the optimum ageing time in relation to an ageing step carried out at 100°C, with the aluminium concentration being kept constant at 2.5%.

The result indicate that at the ageing temperature chosen, and the given ratio of Al:Cl, the optimum ageing time is approximately 30 hours.

Example 8

An aluminium containing solution was prepared in a similar manner to that described above using Aloxicoll-L, aluminium chloride hexahydrate crystals and deionized water to provide a solution having a final Al/Cl ratio of 1.8:1 and a final aluminium concentration of 2.0% by weight. The solution was heated in a closed vessel at 100°C for 24 hours. The aged solution was spray dried immediately using an inlet temperature of 300°C and the range of outlet temperatures shown below. The resulting powders were analysed by SEC and ²⁷A1 NMR, and water content measurements were carried out. Results

These results indicate that, based on the Band III and AlP_x measurements, that the optimum spray drying outlet temperature for this product and this particular drier is in the region of 110°C, which corresponds to a product with a water content of 9.9

Example 9

An aluminium containing solution was prepared in a similar manner to that described above using Aloxicoll-L, aluminium chloride hexahydrate crystals, and deionized water to give a solution having as Al/Cl molar ratio of 1.8:1 and an aluminium concentration of 2.5 wt% . The solution was placed in polypropylene bottles equipped with gas tight screw caps and heated in a fan oven at 100°C for 48 hours. The aged solution was spray dried immediately in a LabPlant SD-04 benchtop spray drier, using an inlet temperature of 250°C and a range of outlet temperatures to give a series of powders with different water contents. An accelerated powder stability trial was conducted by storing the samples in sealed containers at 45°C. Analyses for Band III content were made immediately after drying and again after storage. The results below indicate the loss in Band III as a function of the water contents of the powders .

Results

All samples were stored for 47 days at 45°C, except for the 9.4% water sample, which was stored for 36 days at the same temperature. The losses are expressed as percentages of Band III content initially present in a given sample.

The results show the sensitivity of the powders to the water content and that in order to keep Band III losses below 5% in this test, a water content of less than about 10 wt% is required.

Example 10

An antiperspirant salt with a water content of 9.5% was prepared in a similar manner to the samples of Example 9, although the aluminium concentration used was 1.75 wt% and the ageing time was 24 hours. The sample was subjected to a room temperature storage stability test. The stability of the sample was monitored by SEC and ²⁷A1 NMR. Results

These results further illustrate that samples prepared according to the method of the invention with a water content of less than 10% by weight have good storage stability.

Example 11

In this example an antiperspirant salt was prepared utilising a method generally similar to that described in Example 1 above. Thus, Aloxicoll-L was dissolved with AlCl₃ to provide a solution which had an Al:Cl ratio of 1.8:1 and an aluminium content of 2.0% by weight. The mixture was aged for a period of 24 hours at 100°C, and the solution spray dried. The antiperspirant active salt isolated (water content 9.4 wt%) was incorporated into a roll on composition containing 22% by weight antiperspirant active, 3% Bentone 38, 1% ethanol, 1% propylene carbonate and 73% DC345 volatile silicone.

The compositions were then tested in a hotroom to determine their antiperspirant efficacy, and sweat rate reduction results were obtained for each composition. The method used for evaluating efficacy was that described in US 4,359,456, Test method II (col. 11), except that the panel consisted of at least 30 women who had not used antiperspirant for 17 days before the test; also, in terms of the analysis of data, the % reduction was not calculated for each day separately, and significance was not calculated by applying Duncans Multiple Range Test.

The sweat rate reduction of the antiperspirant active salt produced according to this method was found to be 39.2%, compared to the sweat rate reduction obtained from a commercially available activate aluminium chlorhydrate of 32%.

Example 12

An antiperspirant active salt was prepared and tested in a manner similar to that described in relation to Example 11, except that a solution of HCl rather than A1C1₃ was used. The resulting salt (water content 9.8 wt%) showed a sweat rate reduction of 36.0%, compared to 32% for a commercially available activated aluminium chlorhydrate.

Example 13

An antiperspirant active salt was prepared and tested in a manner similar to that described in relation to Example 9, except that the sample was aged for a period of 19 hours at an aluminium concentration of 1.75% and the sample was freeze dried. The resulting salt (water content 8.7%) showed a sweat rate reduction of 44.0 wt%, compared to 32% for a commercially available activated aluminium chlorhydrate .

Example 14

Antiperspirant salts prepared according to the invention may be incorporated into suspension aerosol products of the following composition using conventional processing methods.

1. D5 (cyclopentasiloxane) grade, eg. DC 245 Fluid.

2. Bentone 38V, ex Rheox.

Example 15

Antiperspirant salts prepared according to the invention may be incorporated into concentrated aerosol products of the following composition using conventional processing methods.

1. ex Rheox.

2. D5 (cyclopentasiloxane) grade, eg. DC 245 Fluid.

Example 16

Antiperspirant salts prepared according to the invention may be incorporated into suspension antipersirant stick products of the following composition using conventional processing methods .

1. DC 345 Fluid, ex Dow Corning. Alternatively, DC 245 Fluid, ex Dow Corning, may be used.

Example 17

Antiperspirant salts prepared according to the invention may be incorporated into soft solid/dry cream products of the following composition using conventional processing methods.

D5 (cyclopentasiloxane) grade, eg. DC 245 Fluid.

Claims

1. A method of manufacturing a polymeric aluminium chlorhydrate having the empirical formula

Al₂(OH)₆__aX_a.YH₂0

wherein X is Cl, Br or I, a is 0.8 to 1.33 and Y is 0.19- 1.4, comprising heating an aqueous solution of the aluminium halohydrate with a solution containing an acidic source of halide ions at a temperature of between 80^SC and 130^SC for a time period of 50 minutes to 10 days, such that the Al/X ratio in the resulting polymer is between 1.5:1 and 2.0:1, and such that the aluminium concentration in the resulting solution is between 0.5 and 3.8wt%, and drying the resultant material to provide a salt having a water content of less than 12wt%.

2. A method according to claim 1, wherein the anion in the polymeric aluminium compound is chloride.

3. A method according to claim 1 or claim 2, wherein a is between 0.9 and 1.2.

4. A method according to any of the preceding claims, wherein the halide is chloride and the acidic source of halide ions is aluminium chloride or HCl .

5. A method according to any of the preceding claims, wherein the composition is heated at a temperature of 95- 105°C for 16-30 hours.

6. A method according to any of claims 1-4, wherein the composition is heated at a temperature of 115-125°C for 2-10 hours .

7. A method according to any of the preceding claims, wherein the ageing step is carried out at 110-130°C for 0.5 to 10 hours and subsequently at 85-100°C for 3 to 48 hours.

8. A method according to any of the preceding claims, wherein the aluminium concentration in the resulting solution is in the region 1.7-3.6% by weight.

9. A method according to any of the preceding claims, wherein the amount of Band 0 polymers in the solution is between 0.5-5.0% by weight.

10. A method according to any of the preceding claims, wherein the ratio of A1:C1 in the final product is between 1.75:1 and 1.85:1.

11. A method according to any of the preceding claims, wherein the water content of the dried salt is in the region 8-12%, more preferably 8-10%.

12. A method according to any of the preceding claims, wherein theaged solution is spray dried.

13. A method according to any of the preceding claims, wherein the resulting antiperspirant active salt has a ratio of Band III to Band II in the Size Exclusion Chromatography Test of greater than 3:1.

14. A method according to any of the preceding claims, wherein the resulting antiperspirant active salt has a concentration of Alχ₃ species of less than 7% by weight, as determined by ²⁷A1 NMR techniques .

15. A method according to any of the preceding claims, wherein the resulting antiperspirant active salt has a concentration of AlP_x species of at least 40% by weight, as determined by ⁷A1 NMR techniques .

16. A method according to any of the preceding claims, wherein the method improves the antiperspirant efficacy of the salt .

17. A method according to any of claims 1-11, wherein the method improves the long term stability of the salt.

18. An antiperspirant active salt comprising a polymeric aluminium salt made according to any of the preceding claims.

19. A topical antiperspirant or deodorant composition for application to the human skin, comprising an antiperspirant active salt according to claim 18.

20. A topical antiperspirant composition according to claim 19, wherein the composition vehicle comprises less than 1% water .