JPH0297598A - Preparation of lowly allergenic lanolin - Google Patents

Abstract

PURPOSE:To produce a lowly allergenic lanolin, by using an enzyme having an esterifying activity to react a lanolin with a fatty acid to thereby esterify an aliphatic alpha,beta-diol contained in the lanolin. CONSTITUTION:An enzyme having an esterifying activity (e.g., lipase or cholesterol esterase) is used to react a lanolin (a mixture consisting mainly of an ester of a higher alcohol and/or a sterol with a higher fatty acid and containing an aliphatic alpha,beta-diol) with a fatty acid (a commercially available 1-20C fatty acid can be used) to thereby esterify an aliphatic alpha,beta-diol in the lanolin. Lanolin, which has been used so far as a base for cream, lotion, etc., and as a medicinal ointment base, may cause some people, although a few, to suffer an allergic symptom. The above-mentioned esterification can produce a lowly allergenic lanolin.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing lanolins with reduced aliphatic-α,β-diols.

(Prior Art) Generally, lanolin is a general term for wool grease (WG), which is a lipid secreted from the sebaceous glands of sheep, which is purified through treatments such as acid treatment, deacidification, decolorization, and deodorization, and has a melting point of 37 to The temperature is 43°C. It is mainly composed of an ester complex of as many as 100 types of lanolin fatty acids and more than 70 types of lanolin alcohol, and has a content of several to 10-odd percent.
It has an extremely complex composition, consisting of alcohols containing some degree of free sterol, a few percent of hydrocarbons, and traces of free fatty acids, making it a unique lipid among natural lipids.

In addition, there are few direct fatty acids of lanolin fatty acids, which are less than 10%, and branched fatty acids such as iso and antiiso are about 27%.
3. Hydroxy fatty acids account for about 1/3. The number of carbon atoms is widely distributed from 9 to 34, and the average molecular weight is about 320.

Lanolin alcohol is composed of alicyclic alcohols such as triterbene alcohol, which mainly contains cholesterol and lanosterol, and accounts for about 70% of the total alcohol. Most of the rest are aliphatic alcohols, which are straight-chain and
It consists of iso-antiisoalcohol and also contains about several percent to ten-odd percent of aliphatic diol. Carbon number is 14-3
The average molecular weight is said to be approximately 370.

For example, lanolin usually has a water content of 200% or more (W/U
: Moisture that 10g of lanolin can contain is calculated by the following formula.

W/U (%) = contained water ffi (m+) / lanolin m
(g) x 100). At the same time, lanolin is also an oily substance and has excellent solubility and dispersibility in various substances.

Taking advantage of these properties, lanolin has traditionally been used as a base for creams, lotions, etc. as an emollient, softener, and superfat agent for the skin. It is also widely used as an ointment base for pharmaceuticals.

Lanolin, which has a complex composition as shown in List L, is significantly different from general animal and vegetable oils and fats in terms of its chemical structure. Lanolin is particularly characterized in that it has properties and properties that are very similar to human sebum.

Although lanolin is generally a safe substance for the above-mentioned uses, there are a small number of patients who experience allergic symptoms. The incidence of this allergy was estimated in 1975 by Clark (E, W., (la.
According to the results calculated by R.K.R.K. based on data from hospitals in three European countries, it is 5.5± per million population.
It is said to be about 4.2 people.

Regarding the search for the causative substance of the lanolin allergy mentioned above, Sulzberger (1953)
M, B) j, J, 1nvestt, Derm
, 20.33-43 (1953) Since then, Clark (
E, W, CIark) [J, Soc, Cosmet, C
hem, 26, 323 (1975), Kaihonro Fragrance Journal, No. 48.60 (19110)]
, Sato Allergy 31 (N.

, 12) 1205-1214 (1982)], Saito [
Skin, Volume 29, Special Issue 3, 252-257 (1987)
] have conducted various studies, and to summarize these studies, the causative substance is found in the alcohol fraction in the constituent components of lanolin.

According to Kaimoto et al., the allergy-causing substances are aliphatic-
They are α, β-diol and α, ω-diol, and the alkyl chains are said to be iso and antiiso forms.

Saito et al. suggest that at least one of the allergy-causing substances is aliphatic-α,β-diol and α,ω-diol, and that there are other causative substances as well.

Furthermore, Sahara et al. conducted a sensitization experiment using guinea pigs and found that the compound is not an aliphatic alcohol or aliphatic diol, but has a lanosterol skeleton, two to three hydroxyl groups, double viscosity, and a ketone carbon. In addition to searching for allergenic substances, various research and development efforts are being conducted on techniques for removing allergenic substances from lanolin to produce hypoallergenic lanolin and its derivatives.

Hypoallergenic lanolin is produced by liquid-liquid extraction with a polar solvent (aqueous solution of lower alcohol), since the allergy-causing substances in lanolin are free aliphatic alcohols and detergents (nonionic activators). Kosho 60
-14796) 1 Similarly, a method of removing components with Rf = 0.38 or less in thin layer chromatography using Florisil as an adsorbent and chloroform as a developing solvent by liquid-liquid extraction (Patent No. 1025372), adsorption column A method of removing polar components by chromatography (Japanese Patent Publication No. 54-21207) is known.

In addition, acetylated lanolin, which is obtained by acetylating lanolin with acetic anhydride and lysine, is known to reduce the likelihood of causing allergies, but it causes severe discoloration during acetylation, and free hydroxyl groups are converted to acetylated by acetylation. Because it is esterified with a group, it becomes highly lipophilic, making it completely different from lanolin, which lacks the water content that is a major characteristic of lanolin.

(Problem to be solved by the invention) The conventional method is to solve the problem of lanolin containing a group of ingredients thought to be allergy-causing substances (all of these are highly polar ingredients, which is a characteristic of lanolin and contributes to its water content). The aim is to obtain a hypoallergenic lanolin by removing these components from lanolin. Naturally, components other than the causative substance are also removed at the same time.
A decrease in yield and a decrease in water content occur.

The water content value (the amount of water that can be contained per unit weight of lanolin, which is usually 200% or more) is a very important property of lanolin, and a decrease in this value significantly reduces the commercial value.

A decrease in yield naturally increases production costs, resulting in economic disadvantage.

In recent years, as a countermeasure against wastewater pollution, there has been an increase in the use of closed-cysteno solvent washing, which does not use water, instead of the conventional method of washing raw wool with water. WG recovered by solvent washing has a high recovery rate since all but the lipids are recovered and does not cause wastewater pollution. However, WG from solvent hair washing tends to have a higher melting point than WG, which is collected by centrifuging the extra lipids from the wastewater emulsion generated by conventional water washing, and some WG may meet the standard even if purified. In some cases, the melting point exceeds /l-3°C, and an economical method for lowering the melting point has been desired.

As a result of extensive research and development, the present inventors have found that the aliphatic-α,β-diol content in lanolin has a close relationship with allergenicity, and that the free content of lanolin can be reduced using enzymes. By esterifying aliphatic-α,β-diols with fatty acids and blocking at least one hydroxyl group, aliphatic-α,β-diols, which are one of the allergens, can be produced.
-Aliphatic -α, without removing the diol from the system
It was found that lanolin with reduced β-diol content could be obtained, and the water content of the lanolin was not reduced, and human patch test results showed that the allergenicity was reduced. The present invention has been completed based on the discovery that esterification of free hydroxyl groups in lanolins or transesterification of ester components can also occur, thereby producing lanolins that meet the above requirements.

(Means for solving the problem) The above problem can be solved by reacting fatty acids with lanolin using an enzyme having esterification activity to esterify aliphatic -α,β-diols contained in lanolin. Alternatively, the problem can be solved by esterifying the aliphatic α,β-diol and esterifying the free hydroxyl group in the lanolin or transesterifying the ester component.

Lanolin used as a raw material in the present invention is a mixture whose main component is an ester of a higher alcohol and/or sterol and a higher fatty acid, and also contains aliphatic α, β-diols, and is obtained by refining WG or it. It refers to the obtained lanolin and its derivatives.

A typical example is W recovered by the solvent washing method.
G, WG recovered by centrifugation, and lanolin purified using these as raw materials.

As a derivative, the main component is ester,
For example, hard lanolin and liquid lanolin obtained by separating lanolin into a solid part and a liquid part by the urea method or solvent fractionation method, partially hydrogenated lanolin obtained by partially reducing lanolin and retaining ester bonds, and similar Examples include treated liquid lanolin, hard lanolin, and various esters made from lanolin fatty acids or lanonon alcohol.

Hereinafter, these will be collectively referred to as lanolins.

All of these lanolins usually contain 1% or less of α,β-diol derived from the raw material WG, and it has been found that there is a strong correlation between this content and the likelihood of developing allergies.

The contents of α and β-diols in lanolins are different.

Although it varies depending on the WG of the raw material, for example, purified lanolin has a content of 0.10 to 0.16%, while partially reduced lanolin tends to have a slightly higher content of about 0.16 to 0.40%. Through partial reduction, the carboxyl groups of α-hydroxy fatty acids present in lanolin are reduced to the corresponding α and β
- It is believed that it converts into a diol.

Since highly polar components tend to be concentrated in liquid lanolin obtained by solvent fractionation, the diol content is generally about twice that of lanolin. On the other hand, hard unonone is slightly lower than the raw material lanolin (0.10-0.12%).
It is.

Relationship between human patch test results and α,β-diol content (see table below; negative means no allergic reaction occurs.Samples marked with an asterisk (*) in the table have α- and β-diol contents obtained by extraction with lower alcohol. , β-diol content is reduced.), it has been found that, for example, in the case of liquid lanolin, if the α,β-diol content is 0.20% or less, the allergy-inducing property is reduced.

This human batch test was conducted using hydrogenated lanolin as a control substance on three patients who developed allergic contact dermatitis due to hydrogenated lanolin (X=j L/).

Try! ! 11! The results may vary somewhat depending on the individual's physical condition, but the test was conducted multiple times, and if no reaction was observed at all, it was considered negative, and if even one case showed a reaction more than slight erythema, it was considered positive.

From the results of similar patch tests, 0.07% is the borderline for lanolin and hard lanolin, and preferably 0.07%.
It was thought to be less than 0.05%.

The present inventors do not consider that α,β-diol is the allergen itself for lanolin, but rather that the main allergens present in lanolin (having some form of hydroxyl group in the molecule) However, we believe that it is more appropriate to consider it as an indicator of

Therefore, based on previous data, it is difficult to determine how low the concentration of α, β-diol should be.
Diol content of 0.07% or less, preferably 0.0
We believe that if it is 5% or less, the allergic potential will be significantly reduced.

The enzyme that can be used in the present invention may be any enzyme that has an esterification activity capable of esterifying one of the hydroxyl groups of an aliphatic α,β-diol.

Therefore, lipase, cholesterol esterase, etc. can be used as the enzyme.

There are two types of novase: those that exhibit positional specificity and those that do not.
Two types are known, but both can be used.

The origin of the lipase and cholesterol esterase is not particularly limited and may be derived from various microorganisms, animals, or plants. Typical sources of lipase include, for example, Achromobacter iophagus (Achromobacter iophagus).
achromobacter 1ofur3us), Achromobacter lipolytica 2% (^chromobacterlelip
Achromobacter species such as Achromobacterium olyticum, Chromobacterium viscosum
um visc.

Chromobacterium genus such as Corynebacterium ac
nes) etc.: 7 Nonebacterium sp., Staphylococcus aureus
Staphylococcus spp. such as Aspergillus us aureus, Aspergillus ni
ger), Candida cylindracea, Candida antakuchi force (Candida ant.
arctica), Humicola species such as Humicola langinosa, Penicillium caseicolum,
Penicillium crustosum
crutosum), Benicillium cyclopium (P
Enicillium cyclopium, Penicillium roueforti and other Penicillium species, Torulopsis sp.
genus Torulopsis, such as S. opsis ernobii),
Mucor genus such as Mucor m1ehei, Bacillus subtilis
Thermomyces 1badanensis, Thermomyces 1badanensis, etc.
), Rhizopus delemer (Rhi
Rhizopus species such as Zopus delemar, Pseudumonus aeruginosa
aerBinosa), Shutomonas fly (P
scudomonus fra3i), Pseudomonas fluorescens (Pseudomonus fl)
Examples include various microorganisms belonging to the genus Shutomonas, such as S. uorescens, and alkaline earth metals (Alcaligenes).

Typical sources of cholesterol esterase include various oral organs of mammals, such as the brain, pancreas, and skin I/3, as well as microorganisms of the genus Shutomonas, such as Shutomonas aerugin-4 and Shutomonas fluores. Achromobacter genus, such as Achromobacter sensu, Shutomonas knob sp.
acterdel 1catulus) etc., Fusariu 2. Genus, Nocardia, Su! - Genus Lebutomyces and Genus Gandida. Examples include Candida lipolytica, Candida tropicalis, Candida intermedia, and Candizosyrinthracia.

Most of the above-mentioned enzymes are commercially available as purified enzymes, and in the present invention, these commercially available products can be used as they are, but it is not necessary to use purified enzymes.
For example, microorganisms themselves capable of producing the desired enzyme, their culture fluids, crude enzyme solutions obtained by processing the culture fluids, compositions containing enzymes, etc. can be used.

Furthermore, these ferments can also be used in a fixed form. The use of immobilized enzymes has the advantage of stabilizing the enzyme (longer life), making it easier to separate the substrate and enzyme, and making it possible to reuse expensive enzymes.

The fatty acid used in the present invention is not particularly limited, and may be a free fatty acid contained in lanolin or a fatty acid added from the outside. Depending on the enzyme used, the activity may vary depending on the chain length of the fatty acid, so care must be taken when combining the enzyme and fatty acid. Carbon number 1-2
Commercially available fatty acids of about 0 can be used.

When attempting to lower the melting point of lanolin, the fatty acid used may be selected to have a low melting point itself, such as unsaturated or branched fatty acids.

When added from the outside, the amount added is preferably adjusted appropriately depending on the purpose. That is, the amount to be added may be determined by considering the type of fatty acid, the melting point of the raw material, etc.

There are several types of hydroxyl groups involved in reactions in lanolins. α, β-diol α position (l treatment) and β position (2
class), hydroxyl group in hydroxy fatty acid ester (secondary class),
These include hydroxyl groups with ester bonds. Regarding the reactivity of these hydroxyl groups, it seems that the α-position (primary) is esterified first, but the order in which the remaining hydroxyl groups are esterified or transesterified depends on the mole fraction of the residues in addition to the reactivity. It is thought that various factors such as , equilibrium relationship, and reaction time are related to this order, and it cannot be determined by one person.

When a hyperactive fatty acid is used, the hyperactive fatty acid may be deoxidized by a conventional method after esterification.

The amount of enzyme to be added may be appropriately determined by taking into consideration enzyme activity, economical reaction time, and the like.

Although the reaction system may be solvent-free, it is preferable to dilute the raw materials with a solvent that does not inhibit the activity of the enzyme, as this will lower the viscosity, improve contact between the enzyme and the substrate, and increase the reaction rate.

Examples of the solvent include hexane, heptane, octane, isooctane (IOC), cyclohexane, decane, hexadecane, benzene, toluene, methyl isobutyl ketone, tetrachloroethylene, liquid paraffin, squalane, squalene, bristane, and mixed solvents thereof, such as Ivytrubene. ) 1016 (manufactured by Idemitsu Petrochemicals), Isopar E (manufactured by Exxon), etc.

Novase is an enzyme conventionally known as a hydrolase, but it is known that the reaction rate of ester synthesis is faster than hydrolysis for hydroxyl groups of hydrophobic substrates such as higher alcohols and sterols. It is being

Cholesterol esterase is also an enzyme conventionally known as a hydrolase. However, the present inventors have found that this enzyme has a higher reaction rate for ester synthesis than hydrolysis for the hydroxyl groups of hydrophobic substrates such as higher alcohols and sterols when a solvent is present in the reaction system. It has been discovered.

The present inventors have similarly found that the reaction equilibrium is biased toward ester synthesis under the above conditions for α,β-diols contained in lanolins. Therefore, in the present invention, there is no particular need to control the water content in the reaction system, and the reaction system may be designed in accordance with the characteristics of the enzyme and enzyme preparation used.

For example, lipase O from Candida syringothrasia
When F is used unfixed, the reaction rate will be higher if it is made into an aqueous solution and used as a water/organic solvent two-phase system than if it is used as a powder. However, when using this by entrapping and immobilizing it with hydrophobic photocrosslinked resin ENTP#4000,
The reaction rate is higher when only a water-saturated organic solvent is used as the reaction system than when the reaction system is a water/organic solvent two-phase system.

It is known that 5P3B2 (manufactured by Novo Industries), which is a thermostable lipase derived from Candida antarctica immobilized in a resin, has maximum enzyme activity when the resin contains 5 to 10% of water based on the weight of the resin. In this case, it is preferable to adjust the resin moisture beforehand and use C.

Similarly, the reaction temperature is preferably set according to the enzyme used. For example, in the case of the above-mentioned heat-resistant 5P3B2, the reaction rate is more than twice as fast at 60°C than at room temperature, but in the case of OF, deactivation is faster, so 30 to 37
℃ is better.

In addition, thermostable enzymes generally tend to have a long enzyme activity life. For example, the present inventors measured the synthesis activity of S P 3 B 2 using cholesterol/oleic acid and found that the initial synthesis activity was 100%. The relative synthetic activity after repeated use 13 times is the first! It has been found that this is 96% of the Ul activity and hardly decreases.

(Example) Hereinafter, the structure, operation, and effect of a typical example of the present invention will be explained, but this example is of course for illustrative purposes and is not intended to limit the spirit of the invention.

The analytical values and human patch test described in the Examples were conducted by the following method.

[Analysis method] GH (Cardona chromaticity): "Standard oil and fat analysis test method" established by Japan Oil Chemists' Association 2.3-1
．． 3-71 Gardna method MP (melting point); JSCI (cosmetic raw material standards)-44 second method AV (value); JSCI-16 SV (saponification value): JSCI-14 (2.0g
4 hour method) OHV (hydroxyl value); JSCI-22 IV (iodine value): JSCI-45 (0.8g
Hanu';', Method) W/U (Water content); Sample 4410 g was placed in a mortar, and a small amount of water was added to it, and the mixture was kneaded into a soft dough. Add a small amount of water while kneading thoroughly, and the end point is the point at which water droplets remain no matter how much you knead.

Water content <χ) = added water 11 (ml)/sample ffi (
g) xloo[α,β-diol-containing coco material is treated with periodic acid, and the formaldehyde generated from the diol is colorimetrically determined by the acetylacetone method a (/
l 10 nm) From the amount, hexadecane-α,
α, β-diol as β-diol is calculated and expressed as a percentage (%) of the sample.

[Human patch test: Cases of allergic contact dermatitis caused by hydrogenated lanolin]
A human patch test was conducted with three subjects as subjects.

Apply a sample of appropriate vinegar to the fin chamber (sample concentration is 10
0%) and was pasted on the inside of the subject's upper arm. Judgment time is 2
It was set as 4 to 48 hours, and 72 to 120 hours. Among all subjects, those who showed no reaction at all were judged to be negative, and those who showed even one reaction of slight erythema or more were judged to be positive. Hydrogenated lanolin was used as a control sample.

J Bozai 11 Manufactured by Storey.

; Heat resistance derived from Mucor Mihei Immobilized lipase. 25 BTU/g, 1,3-regiospecificity can be. Manufactured by Novo Industries.

[Materials used] In the examples, the following were used unless otherwise specified. For enzyme units, the measurement and display methods provided by each manufacturer were used as they were.

Oleic acid: Extraolein #90, Isostearic acid manufactured by Nippon Oil & Fats Co., Ltd.; Lipase OF manufactured by Emery Industries; Lipase derived from Candida syrinthracia, 3
60 U/mg, manufactured by Meito Sangyo Co., Ltd. S P 3 B 2: An immobilized thermostable lipase derived from Candida antarctica. No location specificity. Novoinda Amano P; lipase from Pseudomonas fluorescens, 30 U/mg.

No location specificity. Manufactured by Ohno Pharmaceutical Co., Ltd.

CE: Cholesterol esterase derived from the genus Pseudomonas, 100 U/mg, manufactured by Funakoshi ■.

Example 1 100 g of lanolin and 27 g of oleic acid, iochrome
10 ml of 7A distilled water 500 mg of lipase OF
The dissolved enzyme solution was added and allowed to react at 37°C for 5 days.

The reaction was carried out in a shaking incubator (LR-2, manufactured by Iwasha Biological Science Co., Ltd.) with an amplitude of 70 mm-100=prn.

After 5 days, the reaction solution was allowed to stand for phase separation, and the 10c phase was collected. Appropriate amounts of alkali and a solvent for promoting separation were added to phase 10c, excess oleic acid was deoxidized, and after washing with water, the solvent was distilled off to obtain lanolin in which the hydroxyl process of α,β-diol was blocked. The analytical values and human batch test results of the treated lanolin are shown in Table 1 in comparison with the raw lanolin.

Table 1 From the results, it is clear that the α,β-diol in the raw material lanolin decreased, and at the same time, the human patch test result, which was positive with the raw material, changed to negative. The following can be seen from the changes in general analysis values.

(2) Since the OHV changed from 24.6 to 17.5, approximately 29% of the free hydroxyl groups other than the hydroxyl groups of α,β-diol were esterified. (Calculated assuming that the average molecular weight of lanolin is 672 and that esters with free hydroxyl groups (esters whose acid component is hydroxy fatty acid) are approximately 29%) Despite the above changes, the basic properties of lanolin are W /U is sufficiently highly conserved at 392%.

(2) From the changes in OHV and IV, it can be seen that about 29% of the free hydroxyl groups in the raw lanolin were esterified, and at the same time about 4.5% of the esters were transesterified.

(2) It can be seen that oleic acid is introduced into lanolin by the above reaction, thereby lowering the melting point.

Table 2 From this, it can be seen that the mp of lanolin can be changed by appropriately selecting the fatty acid according to the present invention. The use of saturated fatty acids will increase the melting point, while the use of fatty acids that themselves have a low melting point, such as unsaturated or branched fatty acids, will decrease the melting point.

Example 2 The enzyme solution of Example 1 was treated with lipase OF (200rn
ENTP-OF obtained by entrapping and immobilizing g) with photocrosslinkable resin ENTP-4000 (1 g) 3. Lanolin in which the hydroxyl group of α,β-diol was blocked was obtained in the same manner as in Example 1, except that g was used instead. The analytical values and human patch test results of lanolin after treatment are compared with the raw lanolin and the second
Shown in the table.

From this result, almost the same results as in Example 1 were obtained even when the immobilized enzyme was used, and the α and β-diols in the raw material lanolin decreased and transesterification also occurred. At the same time, the human patch test results were positive for the raw material. It is clear that the result has changed to negative.

Example 3 Immobilized lipase 5P3B derived from Pseudomonas antarctica by adjusting the water content of the enzyme solution of Example 1 to 8%
The reaction was carried out for 72 hours in the same manner as in Example 1, except that isostearic acid was used as the fatty acid instead of 1 g, and lanolin was obtained.

Table 3 Analytical values and human patch test results of lanolin after treatment are shown in Table 3 in comparison with raw lanolin.

When the reaction temperature was changed to 60°C and the reaction was allowed to proceed for 36 hours, almost the same results as in Table 3 were obtained.

Example/l 34.8g of oleic acid in 100g of lanolin.

An enzyme solution prepared by dissolving CElmg in 10ml of distilled water was added to Ocrooml, and the mixture was reacted at 37°C for 116 hours to obtain treated lanolin in the same manner.

The results are shown in Table 4 along with the raw material lanolin.

(Margin below) Table 4 Example 5 Lanolin was obtained in the same manner as in Example 1 using crudely purified WG (manufactured by Tsuzukibo Co., Ltd.) recovered by a solvent washing method using hexane/isopropyl alcohol as a raw material. the result,
The melting point changed from 45°C to 40.2°C, and the α,β-diol improved from 0.13% to 0.04%. Other physical property values also satisfied the standards for lanolin (cosmetic primordium).

Example 6 Lanolin was obtained in the same manner as in Example 1 using the enzymes shown in Table 5. The results are also listed in Table 5.

Although Novozyme in Table 5 is a lipase with 1,3-specificity and Amano P is a lipase without positional specificity, it is clear that these enzymes can similarly reduce the diol concentration.

patent ratio, applicant Kichij Oil Refinery Co., Ltd.

Claims (2)

[Claims] (1) Using an enzyme with esterification activity, lanolin is reacted with fatty acids, and the aliphatic acid contained in lanolin is
A method for producing lanolins, which comprises esterifying α,β-diol. (2) Using an enzyme with esterification activity, lanolin is reacted with fatty acid, and the aliphatic acid contained in lanolin is
A method for producing lanolin, which comprises esterifying α,β-diol and esterifying free hydroxyl groups in lanolin or transesterifying the ester component.