JPS597118A - Skin treating composition - 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 medicinal or cosmetic compositions suitable for topical application to human skin containing fatty acids or esters thereof as active ingredients. The present invention also relates to certain synthetic or purified omega-hydroxy fatty acids and esters thereof with essential fatty acids or derivatives thereof as described below, and derivatives thereof.

As is well known, linoleic acid is a type of natural fatty acid that can be isolated from the skin in free form or as part of a larger molecule. The most common examples of such large molecules include phospholipid 9 and triglyceride P. Linoleic acid is known as an essential fatty acid.

This is because it cannot be produced in-vivo in many organisms and therefore must be present in food.

As used herein, the term "essential fatty acids" refers to n-6,
9- means unsaturated fatty acids.

Previous experiments have shown that when rats were fed a linoleic acid-deficient diet, their physique and general health deteriorated. One of the changes that occurred in this case was that the condition of the skin m deteriorated and the permeation block or permeability barrier within the skin m became worse.
y barrier) function declines, and along with this, epidermal permeation water loss (transepiderma) decreases.
100% (abbreviated as "TFWL") was expected to rise. TEWL by topical application of linoleic acid (linoleic acid in the free state, or linoleic acid present in the form of triglyceride F)
The skin normalized and the skin flakes began to recover after about 2-5 days.

Also, fat malabsorption (malabsorption)
It has also been confirmed that topical application of linoleic acid is effective in patients who develop symptoms of essential fatty acid deficiency due to years of intake of fat-free foods.

Although linoleic acid could potentially have reactivity leading to the production of prostaglandin-like substances, no evidence has yet been found that such a reaction occurs in the skin. When applied topically, linoleic acid is a common class of prostaglandin-like inhibitors (1nhlbit
or ) was found not to interfere with the functional recovery of the permeability barrier within the skin. Furthermore, columbic acid, similar to linoleic acid, has the effect of restoring skin debris and keeping it in good condition, but this columbic acid can never be converted into porcine stubblandin-based substances. was discovered. It is well known that linoleic acid, for example, plays certain roles in phospholipids and triglycerides due to its structure (this role is referred to as a structural role).
Furthermore, it has been argued that linoleic acid must also play some unique role for the formation and maintenance of the moisture permeation barrier.

Therefore, for the molecule contained within the permeation barrier, it is a prerequisite that it (1) contains an essential fatty acid or a derivative thereof, and that it should be present in the epidermis. It has become possible to think that.

Recently, Gray et al. “Blochemica et old phys1caAeta” 528 (1978) 127
A paper published in 137 states that 17 (3'-Q-acyl)-β-glucosyl-N-dihydroxy is ntatoriacontadienoyl sphingosyl (the acyl group is mainly a linoleic acid group) in mammals. Although it has been described that it exists in the skin of people and plays an important role within cell membranes, its properties as a barrier retainer are not described or suggested at all.

0-lyluoyl glucosylcerami F is absent from the stratum lucidum and stratum corneum and is instead present in other esters (i.e. 0-lyluoyl ceramito e) and fatty acids (i.e. O
-riluoyl hydroxy fatty acids) are present in these layers.

These compounds belong to the group of fatty acids and esters having the general formula (1) below, and which when applied topically to the skin improve the function of the barrier within the skin debris. It has been found that this method significantly improves the condition of

When the function of the barrier in the skin is impaired, for example by detergents, or when the function of the barrier in the skin is completely lost due to severe burns, the result is a large amount of moisture removed from the skin tissue. However, for skin in such a state, the composition of the present invention improves the function of the barrier by completely preventing moisture loss from the skin or at least reducing the amount of moisture loss. It has been found that this has the effect of reversing at least a portion of the

Furthermore, even if some of the above-mentioned compounds are present in the skin, the amount present will depend on the solid content (dry matrix) in the skin.
tter) more than 101t-1ji)% of the total -1
It was also found that this was not the case. Therefore, among these metal compounds, those having a purity of less than 10% are outside the scope of the present invention.

Therefore, the present invention provides a suitable vehicle, a fragrance, and the following formula (1) as an active ingredient: (1) where X is H-1CI-C10 alkyl, or is HO-1c1-C4 alkoxy, polyhuman90xylalkoxy, N-sphingosyl and N
-(glycosylsfinbisyl), a is an integer from 7 to 149, and b is an integer from 10 to 98), and Y represents 1 (-1 or the following formula % ) (wherein, 2 is -OH or epoxy oxygen, and X is 1
is an integer from 6 to 20, y is an integer from 24 to 36, and 2 is 0 or an integer from 1 to 4; provided that if 2 is O, γ is an integer from 26 to 36; , or if 2 is an integer from 1-4, then y is 24-
is an integer of 35), provided that if X is H-1 or 01-C10 alkyl, then 1 Y is -〇-( Cx Hy Zz ) CHs and 2 is an integer from 1 to 4. It is about things.

Thus, the active ingredient of the formula % (11) may be a certain fatty acid or substituted fatty acid, acid or ester thereof.

The compositions of the invention may also contain mixtures of these active substances.

The above formula % formula % (1) When Y is 1 -, formula (1) is the ω-hydroxy fatty acid of the following formula HO-8-(CaH,)OH (21) or the following formula % formula % (3) of carboxy-substituted -ω-humano-roxy fatty acids.

The ω-hydroxy fatty acid (2) can have a carbon chain of 8-50 carbon atoms and contain up to two olefinic type 2 bonds.

The value of a in the above formula is 23-37, most preferably 2
9-33, ideally 31-33, and the value of b is 42
-74, most preferably 54-66, ideally 58-
66 is preferred.

The general formula (the preferred one among the 2-costal ω-hybyloxy fatty acids is the following formula % formula % (4) [where d is an integer of 0-46, e is an integer of 0-46, and d+e is 4 -46, f is an integer of 1-2, the total length of carbon atoms is 8-50 (not expressed in number of carbon atoms), and this carbon chain has one olefinic bond. or two] is an ω-human 90-x unsaturated fatty acid.

carbon chain length 24-38, most preferably 30-3
4, ideally 32-34 (expressed in number of carbon atoms)
ω-hydroxy unsaturated fatty acids whose value of f is more preferably 1 are preferred.

Therefore, the most preferred ω-hydroxy unsaturated fatty acids have one olefinic type 2 bond and have the following formula % formula % (5) where p is a number of 21-23 and q is a number of 6-8 A monounsaturated ω-hydroxy fatty acid (a fatty acid having one zunaitsuchi olefinic type 2 bond) that can be represented by the following number.

Examples of the ω-human 90x unsaturated fatty acids having formula (4) include the following.

ω-Hydroxy-6-cysuto-9decenoic acid (fl) ω-
Human 90x-21-cis-triacontinic acid
(7) ω-human 90x-23-cis-triacontinic acid
(8) ω-hydroxy-23-shoot 9-triacontinic acid
(9) ω-hydroxy-25-shoot 9-triacontinic acid
00) ω-human 90x-25-tetratriacontinic acid
αυω-HyFroxy41-cis-bentaacontenoic acid (
121 Carboxy-substituted -ω-human 90 with formula (3)
Particularly preferable among the xyunsaturated fatty acids are the following formula %
A compound having the formula %(13) wherein the compound is selected from cl-C4 alkoxy, polyhydroxylalkoxy, N-sufinbicil and N-(glycodylsphin!cyl).

Among the aforementioned carboxy-substituted -ω-hydroxy unsaturated fatty acids, specific examples of fatty acids in which R is cl-c4 alkoxy include those having the following formula % formula % (14). Examples of the aforementioned fatty acids in which R is a polyhydroxyalkoxy residue such as a mono-substituted glycerol residue include those having the following formula: Examples of the above fatty acids in which R is a polyhydroxyalkoxy residue such as a substituted glycol residue include those having the formula: Examples of the above fatty acids in which R is a polyhydroxyalkoxy residue such as a substituted inositol residue include those having the formula: Examples of the above fatty acids in which R is a polyhydroxyalkoxy group such as a sugar residue (for example, a glucose residue) include those having B. However, equation (25) and (
In 2Q, at least one B is a group of the following formula %) ( ), and the remaining B are II- or C2-C24 acyl groups.
Examples of u, converted fatty acids include those having the following formula (where 8 is a number from 12 to 14). Examples of the above substituted fatty acids in which R is an N-(glycosylsphingosyl) residue include the following formula % Formula % Preferred N-(glycosylsphingosyl)-substituted-ω
-Hi-10xy unsaturated fatty acids are the above fatty acids in which the glycosyl type substituent bonded to one sphingosyl residue is a glucosyl group.

The above formula a1. (21J, @ and Q forces, rt, rl' and y" have the same or different values as the value of p, and have the same or different values as v, r' and 2'r6.

In the above formulas US-Oυ and (c), A is H- or Anru.

F! L sender 9 Mr. X -0-y In (1),
is H- or C1-Cto alkyl, and Y is the following formula % formula %) −
C-(Cx Hy Zz) CHg Q! J
hydroxy or epoxy derivatives of essential fatty acids, or the alkyl fatty conductor of the formula % (31).

In Shikikan, 2 is an integer of 1-4, that is, 1-
If four hydroxyl or epoxy groups are present, these groups can be present next to or near any olefinic type 2 bond that may be present in the formula, or they can be present on any carbon atom. It may be combined with

Examples of the hydroxy derivatives of the above essential fatty acids include the following.

9.10.13-Trihydroxy-1'1-octadecenoic acid OD9.12
．． 13-) Lyhydroxy-10-octadecenoic acid
t3'IJ9-hydroxy-
10,12-octadecadienoic acid
(to) 13-hydroxy-9,11
-octadecadienoic acid
04) 15-Hydroquine-5,8,11,13
-Eicosatetraenoic acid (c)
11.12.15-) Lich Pro Roxy 5.8° 13-eicosatrienoic acid (36) 6.7,1
2.13-tetrahydroxy-8゜10-octadecadienoic acid 0η9-hydroxy-12,13
-Oxo'-10-octadecenoic acid °
15-hydroxy-11.12-oxide-5
゜8.13-eicosatrienoic acid (to) In the already mentioned formula % formula % (11), X is a group of the following formula 1 R-C-(CB)1b)-, and Y is a group of the following formula % formula % all-cis n-6% 9-fatty acid or its derivatives, formula (1) is converted to the following formula R-C-(Ca)
Ib)-0-C-(CxHyZz)c)I3
II represents an ester of an ω-hydroxy fatty acid or a carboxy-substituted derivative thereof with an essential fatty acid or a hydroxy or epoxy derivative thereof. It may have a structure in which an ω-hydroxy fatty acid is condensed with an essential fatty acid or a hydroxy- or epoxy-substituted essential fatty acid via the ω-hydroxyl group.

The structures of the ω-hydroxy fatty acids (including their carboxy substitutes) and the hydroxy and epoxy μ conductors of essential fatty acids have already been described.

As is clear from the above definition, the essential fatty acid residues that may constitute a part of the ester are expressed by the following formula (41) (where KX is an integer of 16-20 and y is 26-36).
all-cis n-6,9-fatty acid residues derived from essential fatty acids with carbon chains containing 18-22 carbon atoms and having up to 6 olefinic type 2 bonds The above essential fatty acid residue preferably has two cis-olefin type 2 bonds, but has 3-4 olefin type 2 bonds, two of which are 11-6.
9 positions, the third or fourth one being n-
It may also be a fatty acid residue derived from a 5-fatty acid present at the 12th to n-155th position.

Other examples of such essential fatty acids include:

Octadeca-(n-6,9,12)-)rienoic acid (42
1: A specific example thereof is γ-lylunic acid, in which each double bond is in the cis configuration.

Eicosa-(n-6,9,12)-)rienoic acid (431
: A specific example thereof is dihomo-r-lylinic acid, in which each double bond is in the cis configuration.

Octadeca-(n-6,9,13)-)rienoic acid 041
A specific example is columbimenic acid, in which the double bonds at the n-6 and n-9 positions are in the cis configuration, and the double bond at the n-13 position is in the trans configuration. It is something.

Eicosa-(n-6,9,13)-)rienoic acid (41;
In a specific example, the double bond at the n-6 and n-9 positions is in the cis configuration, and the double bond at the n-133 position is in the trans configuration.

Eicosa-(n-6,9,12,15)-tetraenoic acid (4e); a specific example thereof is arachidonic acid, in which each double bond is in the cis configuration.

It has 3-6 2'M bonds, three of which are (n
Essential fatty acid groups derived from essential fatty acids in the -a*6+9) position can also be used.

Examples of such essential fatty acids include:

Octadeca-(n-3,6,9)-1-ly"M(47
1; a specific example thereof is 7 + 11 phosphoric acid, in which each double bond is in the cis configuration.

Eicosa-(n-3,6,9,12,15)-pencitric acid (4S);
nodonicacid), in which each double bond is in the cis configuration.

Docosa-(n-3,6,9,12,15,18)-hexaenoic acid (4 (to); a specific example thereof is sardine acid,
Each double bond in this case is in the cis configuration.

Examples of Esters of the Invention Some examples of esters suitable for use in the compositions of the invention include:

30-34 carbon omega-(○-liluoyl)-fatty acid or its carboquine having the following formula % formula % (where p is a number from 21-23 and q is a number from 6-8) Substituted Derivatives 1. Specific examples of this group of esters include:

The following formula %formula% (51) ω-(0-liluoyl)-C52 fatty acid having the following.

The following formula %formula% ) (52) ω-(O-liluoyl)-C54 fatty acid having the following.

An ω-(O-columbinoyl)-C12 fatty acid having the following formula: % (53)

ω-(O-arachitonyl) -Cso Fat Q with the following formula % formula % (54)
ω-(O-liluoyl)-ceramide having the L formula % ) (55).

ω-(O-arachitonoyl)-glucosylceramide having the following formula % formula % (56).

ω-(O-liluoyl)-glucosylceramide having the following formula % formula % (57).

Following formula % formula % 0 111...C-(CH2)FCHOH-CHOHCH-CH
-CIO(CH2)4CH3(58)
-octadecenoyl)ceramide.

ω-(0-9-Hydroxy-12,13-oquinodo-10-octadecenoyl)-C32 fatty acid having the following formula % formula % (59).

ω-(○-15-Hydroquine-11°12+endo5.8.13-eicosatrienoyl)-ceramide having the following formula: (60)

ω-(9,1o,+3-trihydroquine-11) with the following formula % formula % ) (61)
-octadecenoyl) -C32 fat/174'.

An ω-(O-columbinoyl)-C32 fatty acid having the following formula % ((2)).

The following formula %formula% ) (63) ω-(0-columbinoyl)-ceramide having the following.

ω-(〇-γ-lilnoyl)-C32-fatty acid having the following formula %.

The following formula %formula% ω-Co-r-lylnoyl)-ceramide having the following.

Following formula % formula % 0C 1( ...C(CH2)3 (CI(=CH-CH2)
ω-( with 4(CH2)s CHs (66)
O-arachitonoyl) -C34 fatty acid.

The following formula %formula% (67) ω-(O-arachitonoyl)-ceramide having the following.

Ethyl-9,10,13-trihydroxy-1 having the following formula (68)
1-Octadecenoate.

The amount of active ingredient or mixtures thereof incorporated with a suitable vehicle in the composition for topical application can vary within a wide range, but the amount of active ingredient generally falls within a range of 001-5fold li,%, preferably 0.
0.01 to 0.1 kg (based on the weight of the composition), and this amount would be an appropriate and effective amount to be applied to the skin when applied topically to the skin.

Vehicle The composition should also contain a vehicle that is capable of delivering the active ingredient to the skin in a progressive dilution.

The vehicle for the active ingredient incorporated into the compositions of the invention can be selected from a wide variety of botanical substances depending on the desired dosage form of the composition. Suitable vehicles can be classified as described below.

Vehicle means a substance that can act as a diluent, dispersant or solvent for the active ingredient, thus ensuring that the active ingredient can be applied to the skin at 5 VcL,
, and has the function of ensuring that the active ingredients are distributed homogeneously on the skin at appropriate concentrations. Preference is given to vehicles that can aid in intrarectal penetration of the active ingredient and ensure longer efficacy of the active ingredient by improving the substantivity of the active ingredient to the skin. The compositions of the invention may contain as vehicle water and/or vehicle substances (other than water) that are acceptable as cosmetic ingredients.

Examples of vehicles other than water that can be used in the compositions of this invention include various liquid and solid substances such as emollients, propellants, emollients, emollients, thickeners, and the like.

Specific examples of various vehicles of the ntJ type that can be used alone or in admixture with one or more carriers are given below.

Emollients such as stearyl alcohol, glyceryl monolysylate, glyceryl monostearate, Furono Guno 1. Seadiol, butane-1,3-:)ol, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, inbutyl/Q lumitate, incetyl stearate, oleyl alcohol, isopropyl laurate, hequin laurate, denyl oleate , octadecane-2-ol, isocetyl alcohol, cetyl alcohol, dimethylpolysiloxane,
Di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, castor oil, acetylated lanolin alcohol, petroleum, mineral oil, butyl myristate, isostearic acid , /Q lumitic acid, isopropyl laurate, lauryl lactate, myris lulactate, denyl oleate, myristyl, myristate.

Propellants, such as trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, trichlorotrifluoroethane, propane, butane, isobutane, dimethyl ether, nitrous oxide with dioxide return.

Solvents such as ethyl alcohol, methylene chloride, isoproanol, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether monoethyl ether, dimethyl sulfoxide, tetrahydrofuran.

humectants such as glycerin, sorbitol, sodium-2-pyrrolidone-5-carboxylate, soluble collagen, dibutyl phthalate,
gelatin.

Powders such as chalk, talc, drift earth, kaolin,
Starch, gum, colloidal silicon dioxide, sodium polyacrylate, tetraalkyl and 7-year-old trialkylaryl ammonium smectite, chemically modified magnesium aluminum nosilicate, organically modified montmorillonite clay, hydrated aluminum nosilicate,
Fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate.

The amount of vehicle (including water, if present) in the composition is such that the amount is sufficient to effect the skin, yet sufficient to deliver at least a portion of the active ingredient to the skin. Preferably, the amount is %, and when the amount of other components is negligible or zero, the amount of vehicle may be such that it accounts for the majority of the composition.

Therefore, this composition contains a vehicle of 50-99,
It may contain 99'6% by weight, preferably 90-99.5% by weight.

Perfume The composition of the present invention may contain a sufficient amount of perfume to render it pleasant to use by a demyelinator. Generally, fragrance is 0. o 1-10i-JR% (based on the weight of the composition) can be blended.

Other Components The composition of the present invention may appropriately contain components other than those described above, depending on its desired dosage form. For example, it may contain preservatives, deterioration inhibitors, antioxidants, emulsifiers, colorants, detergents, and the like.

The compositions of the invention can also be used as vehicles for various types of cosmetic or medicinal active ingredients, especially those that impart a certain betel effect on the skin.

Thus, the compositions of the present invention can serve as a means for diluting, fractionating, and delivering the various active ingredients described above to the skin surface where they are distributed in appropriate concentrations.

The present invention also provides a composition for topical application to the skin, characterized in that the active ingredient as described above is mixed with a suitable vehicle to produce a composition with an active ingredient concentration of 0.001-0.5%. The present invention also provides a method for producing a cosmetic composition.

The compositions of the present invention can be prepared in the form of liquids such as lotions or milks. Such liquids are rolled
It can be applied to the skin using an applicator, such as a pole applicator, or an ejector, such as an aerosol can containing a propellant, or a container with a pump for dispensing the liquid product. Alternatively, the compositions of the invention may be solid or semi-solid, such as sticks, creams or gels, which are applied to the skin using a suitable applicator, such as a tube, bottle or lidded jar. Alternatively, the composition can be applied to a liquid-impregnated fabric, such as a tissue wipe.
It can also be used in form e).

Of particular importance in the compositions of the invention, which may be medium oil emulsions, are aqueous fat emulsions in which the aqueous phase acts as a carrier.

Topically applied medicinal compositions are important in %. This is because the condition of the skin depends on the presence of essential fatty acids. Such compositions may be liquid or plastic.

Examples of liquid or plastic compositions include:

Liquid compositions comprising said esters of the invention, with or without carrier oil; comprising said esters of the invention in free state or in fatty conductor form in a physiologically acceptable bath medium. an aqueous solution or emulsion of the ester;
Cream preparations and ointments, such as plastic dispersions, comprising the esters in the free state or in the form of a salt conductor, dispersed in a suitable carrier, for example in a soft base. Such compositions are useful as prophylactic and therapeutic agents for skin disorders caused by contact with detergents, and also as therapeutic agents for environmental trauma caused by weather conditions, sunburn, or other types of feces. It is also useful as an agent for reducing bacterial activity on the skin. These compositions are also useful as therapeutic agents for skin exhibiting essential fatty acid deficiency symptoms due to fat malabsorption in the gastrointestinal tract, for example, and for skin affected by fish rot.

The invention therefore also provides a closed container containing a cosmetic composition as defined above.

The compositions of the present invention are suitable for topical application to human skin, especially when the skin surface becomes excessively dry, causing some itchiness or irritation. Or suitable for topical application when other injuries occur.

Accordingly, the present invention also provides a method for topically applying the compositions of the present invention to humans suffering from or predisposed to essential Nh acid deficiency or other skin diseases. The dosage of the composition will vary depending on the method of administration and the conditions being treated. 4 The dosage of the composition is generally 1
00 μg (the above ester)/cn! (skin) or 1
000μII (the above ester)/cr! (skin), and this dose is 10 μg (said Nisdel).
/cnl (skin m) to 100 μg (the above ester)/
The dosage is sufficient to keep the esters of the leaves of P. d (skin 1-) on the skin, thereby providing a sufficient amount of essential fatty acids to maintain normal skin condition. Local skin indications may necessitate one or more administrations of this dosage.

The present invention also provides the aforementioned active ingredient and an autooxidation inhibitor in an amount capable of effectively preventing autoxidation of the ester.
Compositions containing, for example, butylated p-cresol, butylated hydroquinone monomethyl ether or tocopherol are also provided. The antioxidant must be physiologically acceptable. This antioxidant is 0.005% based on the amount of the ester.
-5 weight can be present.

The present invention also provides the use of the active ingredients as described above for the topical treatment of skin diseases (
The present invention also provides methods for use in treatment.

Next, examples of the present invention are not shown.

(Hereafter 1, blank) Example 1 This example is a high internal phase type (high internal phase) containing the ester of the present invention.
This is an example of a water-in-oil emulsion.

A high internal phase type water-in-oil type 1 and 1j having the following formulation composition was prepared.

%W/W Fully Hydrogenated Coconut Oil 3,9Brlj
92” 5 Benton aB
o,s preservative
0.3Mg 804 Self 71110
0.3 Zotylated hydroxytoluene 0.01 Fragrance
Appropriate amount of water Remaining total amount: 100% Br1392 is polyoxyethylene (2) oleyl ether.

Example 2 This example also illustrates a high internal phase water-in-oil emulsion containing the ester of the present invention. This emulsion was prepared according to the formulation of Example 1 except for the following points.

(1) Liquid paraffin was used in place of fully hydrogenated coconut oil.

(Ill ester was ω-(0-lyluoyl)-ceramide of formula (55).

Example 3 This example was also prepared containing the ester of the invention.

That is, the ester used here was ω-(0-lyluoyl)-glucosylceramide of formula (57).

Example 4 This example 9tl was made in water containing the ester of the invention.

%W/W Mineral oil 4 Brij 56° 4 Anoshi7ol 16 RD” 4 Triethanolamine 0.75 Zotan-l,3-,)ol 3 Xanthan gum
0.3 Preservatives 0.4 Flavors Appropriate amount of dithylated hydroxytoluene 0. O1 water
Remaining panoramic view 100 Ml "Br1356" is cetyl alcohol POE
(10).

Qinqin°1 Alfol 16RD' is cetyl alcohol.

Example 5 This example also illustrates an oil-in-water emulsion containing the ester of the invention. This was manufactured according to the formulation of Example 4 except for the following points.

That is, the ester used here was ω-(0-columbinoyl)-(Js* fatty acid) of formula (53).

Example 6 This example also illustrates an oil-in-water emulsion containing the ester of the present invention. This emulsion was prepared according to the formulation of Example 4, but this time the formulation was changed as follows. .

That is, the ester used this time has the formula (56) ω-(0-arachitonoyl)-glucosylcera ξP
It was.

Example 7 This example illustrates an alcoholic lotion containing the ester of the present invention.

The conor lotion had the following composition.

Ryo W/W Ethanol 4°Fragrance Tsurugi Dithylated Hydroxytoluene 0.01 Water
Remaining total amount: 100 Example 8 This example shows the alcohol-A/
This is an example of the system C1-John.

This lotion had the following composition.

%W/W acid dimethyl sulfoxide lO ethanol
40 Antioxidant 0.1 Fragrance
This is a lotion that can be used for 4 parts water and the rest 11:100.

%W/W 9 10 Noyl)-ceramide fragrance 0.1 0.1 Hydroxyethyl cellulose 0.4 0.
4 Absolute ethanol 2525p-methylbenzoate 0.2 0J sterile distilled water Remainder Remaining total amount 100
100 Examples 11-12! The composition of the invention described below is suitable for the treatment of dry skin.
It is a lotion that can be used for.

Nine W/W 11 12 Ethanol 10 10
Fragrance 0.5 0.5 Distilled water Remaining balance Total @ 1
00 100 The composition of the invention described below is a cream composition that can be used for the treatment of skin burns.

%W/W i314 Cetyl alcohol 88 Mineral oil
4- Rough-in wax -2 Xanthan gum 0.3 0.3 Preservative
0.4 0.4 fragrance
Appropriate amount Appropriate amount of distilled water
Remainder Total amount remaining 1oo io.

The composition of the invention described below is suitable for the treatment of dry skin.
It is a lotion that can be used for.

%W/W 15 16 Ethanol 4545 Fragrance
Appropriate amount Appropriate amount of water
Remaining amount Remaining amount too to.

These Examples illustrate the intraisland phase type water-in-oil emulsion composition of the present invention.

Each emulsion consisted of 10% by volume of an oily phase and 90% by volume of an aqueous phase having the following composition:

Oily phase % W/W Sorbitan monooleate 20 quaternium-18-hect2ite 5 Liquid paraffin 75 Aqueous phase % W/W Active ingredients "o, s xanthan gum 1 Sodium chloride (1% W
/W solution) 98.2 Anti-dust agent
0.3 Fragrance Conductive Qin The active ingredients were as follows.

Example 17: ω-(0-T-lilnoyl)ceramide of formula (65) Example 18: ω-(0-arachito/yl)C34 fatty acid of formula (66) Example 19: formula (67) ω-(0-arachitonoyl)ceramide Each of the compositions described in each of the examples described above can reduce skin water loss and also restore damaged skin. and/or on the skin, especially on skin rough or burnt with detergents, in order to improve the function of said inhibitors in the skin so that hydration is possible.
It can be applied topically.

The present invention also includes: The present invention also relates to novel shaped ω-hydroxy fatty acids and derivatives thereof, and also to novel esters formed by the reaction of such ω-hydroxy fatty acids with polarized essential fatty acids or their hydroxy- or epoxy derivatives.

Therefore, the present invention provides the following formula % formula % (1) [where X is the following formula 1 1L -0-(O1l/Hb/ ) -(in the formula, a16
is an integer of 27-33, %b1 is an integer of 5G-64, R is HO-1O, -04 alkoxy, polyhydroxyalkoxy V, N-sphinbisyl, and N-(glycodylsphingosyl) 11- (J-((JxH,Z,)alt=(wherein, 2 is -011 or epoxy oxygen, X is 16-
It must be an integer of 20, and y must be an integer of 24-36! is 0 or an integer of 1-4; provided that %R is HO-1
or O,-(J, when alkoxy, Y is 1 U-(0xHyZ z ) UHs), the residue of an all-cis n-6,9-fatty acid or a derivative thereof] Also provided are novel synthetic or purified fatty acids and their esters with a purity of 10%.

In the above formula % formula % (1), X is a group of the following formula 1 RU - (Oa'Hb') -, R is HO- or Ul-04 alkoxy, and Y is In the case of H-, formula (1) represents an ω-hydroxy fatty acid of the following formula (%).

Therefore, ω-hydroxy fatty acid (69) has 2 carbon atoms
It has an f carbon chain consisting of 8-34 carbon atoms, with 1-
may contain two olefinic type 2 bonds, preferably this is expressed by the following formula: where d' is an integer from 0-24, e'fio-24, and d '+e'
is an integer between 24 and 34, and f is an integer between 1 and 2)
It has the following.

The version is also preferred, where 1 of f is 1, and in this case, the fatty acid is expressed by the following formula % formula % (5) (where p is an integer from 21 to 23, and q is 6 The monounsaturated ω-hydroxy fatty acids (which is an integer of -8) are mentioned.

ω-hydroxy-21-cis-triacontinic acid
(7) ω-hydroxy-23-cis-triacontinic acid
(8) Ol-hydroxy-2
3-cis-todriacontinic acid
(9) ω-Hydroquine-25-cis-todriacontinic acid
00) ω-hydroxy-25-tetratriacontinic acid
0υ In the formula % formula % (1) described above, X represents a group of the following formula 1 RU - (UaHH) -, and R represents polyhydroxyalkoxy 7
, N-sphingosyl and N-(glycodylsphingosyl), and when Y is H-, formula (1) is converted to the following formula 1 H,-0-(OaH,) OH (3) (where a is an integer of 7-49 and b is an integer of 10-98) represents a carboxy-W-converted-ω-hydroxy fatty acid.

Particularly preferred calzoxy-substituted-ω-hydroxy fatty acids have the following formula 110-(UHI)a(UH-011-(JHl)f
((JHl) eOHQl (where d is an integer from 0 to 46, e it is an integer from 0 to 46, d + e is an integer from 4 to 46, and f rj is an integer from 1 to 2. The total carbon chain length of this acid is 8-50 carbon atoms.
and this is 1-21b'i
It contains an olefinic divalent bond of 1.

Preferred examples of the carboquine-substituted -ω-hydroxyunsaturated fatty acids include the following.

Formulas (14) and (15) in which R is 01-ψ4 alkoxy
, (16) or (17); compounds of formula (18), (19), (2) wherein IL is a polyhydroxylalkoxy residue such as a substituted glycerol residue;
0), (21) or (22); a compound of formula (23) or (24) in which R is a polyhydroxyalkoxy residue such as a substituted glycol residue; Compound of formula (25) which is an alkoxy residue; R is a saccharide residue (
A compound of formula (26) in which R is a dihydroxylalkoxy residue 4 such as a glucose residue; a compound of formula (27) in which R is an N-sphingosyl residue; R is an N-(glucosylsphingosyl) residue; Formula (2
8) Compound.

In the above formula (1), X is a group of the following formula 1 a-o-(08H,) -, and Y is an all-cis n-6,9 group of the following formula - in the case of a residue of a fatty acid or a derivative thereof, formula (11) represents an ester l of an ω-hydroxy fatty acid of formula (40) or a carboxyne-substituted derivative thereof with an essential fatty acid or a hydroxy or epoxy derivative thereof; become.

Particularly preferred examples of new Nisdel include the formula 1 formula (%) already described. Specific examples of particularly preferred esters include the formula (51)
- (68) is mentioned.

The ω-hydroxyunsaturated fatty acids of the present invention can be synthesized by performing a total synthesis operation according to standard polyunsaturated fatty acid synthesis methods, for example, carrying out an acetylene coupling reaction, followed immediately by a selective semihydrogenation reaction. It can be synthesized by performing

The ω-hydroxy fatty acids of the present invention can be produced using ω-ethylenically unsaturated fatty acids having, for example, 8-12 carbon atoms in the molecule as a starting material. That is, this starting material is brominated, for example, by adding one molecule of Br to the double bond.
(bromination by addition of hydrogen) followed by dehydrobromated scheelite, resulting in ω-acetylenically unsaturated fatty acids (in this compound, the acidic hydrogen of the acetylene group is replaced with bromine). have) obtained [to do]. This ω-acetylenically unsaturated fatty acid can be treated with lithium aluminum hydride, thereby yielding the corresponding ω-acetylenically unsaturated aliphatic alcohol.

The alcohol derived from the ω-acetylenically unsaturated fatty acid and the bromide compound are
Ict ) can be condensed by a coupling reaction, which gives a diacetylenically unsaturated ω-hydroxy carboxylic acid with a carbon chain length corresponding to 16141 f&l carbon atoms, which on reduction gives the corresponding ω-hydroxy saturated Fatty acids are obtained.

Additionally, a condensation reaction can be carried out to increase the chain length, which involves the zolomo or 0-tosyl derivatives of the 01·-0v4ω-hydroxy saturated fatty acids described above and the 'J
l-(111ω-acetylenically unsaturated aliphatic alcohol molecules, and when carrying out this reaction, it is best to appropriately protect the terminal hydrogen and hydroxyl groups. The resulting condensate contains 24-36 carbon atoms, and by subjecting it to a partial hydrogenation reaction, the acetylenic bonds are reduced to olefinic bonds, i.e., the ω-hydroxy monounsaturated Fatty acids are obtained.

As a specific example of the above-mentioned production method, a production method for preferred compounds of the present invention, ω-hydroxy unsaturated fats, acids, and their n-cyclic forms will be described.

Synthesis of ω-hydroxy-23-cis-todriacontinic acid The starting material for the synthesis of ω-hydroxy 031 monounsaturated fatty acids is ω-ethylenically unsaturated 011 fatty acids. This is first brominated according to the method described above, and then subjected to a debrominating aqueous reaction to produce the corresponding ω-acetylenically unsaturated fatty acid according to the reaction formula below.

HOE=O(OIb)aoooh ('
12) The above acid (72) is immediately treated according to the following two methods. That is, this tl- is first brominated with potassium hypobromite to produce the Zolomy 14 derivative (73) of the following formula (7).

In the second run, acid (72) is converted to the corresponding ω- and droxy-substituted acetylene compound using lithium aluminum hydride.

This compound has the following formula % formula % (74), then teic acid (73) and ω-hydroxyacetylene compound (
74) between Oadlot- (Jhodkiewie
A z-coupling reaction was performed to obtain diacetylenically unsaturated -ω-hydroxycarzeneic acid (
75) is generated.

Complete hydrogenation of the diacetylenically substituted compound (75) with gives the ω-hydroxy fatty acid (76) of the following formula % formula % (76).

By further reacting this with 4-toluenesulfonyl chloride, a tosyl derivative of acid (76) is obtained, and the latter compound can be represented by the following formula (77). This tosyl derivative (77),
Lithium-substituted ω-hydroxyacetylenated 4 & compound (78)
78) [the ω-hydroxyl group of compound (78) should be appropriately protected], and then, after removing the protective +lJ group, the acetylenically unsaturated 03! -ω-hydroxy fatty acid (79) is obtained.

This reaction is carried out using the following formula (% formula %) (79) The partial hydrogenation reaction of ω-hydroxyfat #& (79) is carried out in ethyl acetate over a phosphorus Y-ra catalyst in the presence of pyridine, resulting in the following reaction: Formula HOOO(OH1 stone(]H
= (IH(OH*)sOH(80) ω-hydroxy-
23-cis-todriacontinic acid is obtained.

Benzoylsphingosine can advantageously be used as a starting material in the synthesis of sphingosyl ω-hydroxy-23-7 pseudotriacontenate, which is described in "J.
Org, Ohem,” 46, 4393 (198
It can be manufactured by the manufacturing method described in 1).

From this benzoylsphingosine, the benzoyl group is first removed under the action of a base. Then you can play. Separately, ω-hydroxy-23-cis-todriacontinic acid (8o) obtained by the method described above was prepared, and this was first added to the ω
- hydroxyl functional group is inserted using resophosphoric acid,
Next, sphingosyl ω-hydroxy-23-cis -Todria contenate (83) is obtained according to the following reaction formula.

Fiber + Exposure (JH, OH...0(OYl,)Full10H=(IH(O
i (1) 100 (83) 1-〇-henzoylsufinbicin can be advantageously used as a starting material in the synthesis of the above compounds, but the free 3-hydroxyl of the tertiary zotyldimethylsilylchloride p (
1. Attach and protect a conservation group by reaction with TBnus-oz). After removal of the benzoyl group under the action of a base, reaction with tetraresodinoylzolo9; dulcose produces linoylglucosylsphingosine (84).

After carrying out the condensation reaction of the glucosyl sphingosine (84) with the acyl chloride (82) and then removing the protecting group, the following formula % formula % (85) glucosyl sphingosine is obtained.

The esters of the present invention can be synthesized by total synthesis according to standard synthetic methods for the synthesis of polyunsaturated fatty acids. This synthesis method can be carried out, for example, as follows:
That is, after the acetylene coupling reaction, semiureation and condensation reactions of fatty acid residues are carried out, thereby producing an ester between the ω-hydroxy fatty acid and the essential fat.

That is, in the above method, the ester of the present invention is produced by condensing the ω-hydroxy fatty acid with the essential fatty acid, but the ω-hydroxy fatty acid itself can be produced by the following manufacturing method. -Hydroxy fatty acids can be produced by the following procedure 9 using OJ-ethylenically unsaturated fatty acids having, for example, 8-12 carbon atoms in the molecule as a starting material.This starting material is brominated. For example, bromination is carried out by adding one molecule of Br! to the two-wheel bond), followed by a dehydrobromination reaction to produce the corresponding ω-acetylenically unsaturated fatty acid. This unsaturated V can be immediately brominated using potassium hypobromite, resulting in an ω-' acetylenically unsaturated fatty acid (in this compound, the acidic hydrogen of the acetylene group is replaced with bromine). , this ω-acetylenically unsaturated fat l! W can be treated with lithium aluminum hydride to yield the corresponding ω-acetylenically unsaturated aliphatic alcohol.

The alcohol derived from the ω-acetylenically unsaturated fatty acid and the bromide compound are 0adiot
-Ohodklewlcz can be condensed by a Cassilling reaction, which gives diacetylenically unsaturated ω-hydroxy fatty acids with a carbon chain length corresponding to 16-24 carbon atoms, which on reduction give the corresponding Monohydroxy saturated fatty acids are obtained.

Additionally, condensation reactions can be carried out to increase the chain length;
The method is to react a bromo- or 0-)yl derivative of a saturated fatty acid with a molecule of the US-U, ω-acetylenically unsaturated aliphatic alcohol, and when carrying out this reaction, the terminal hydrogen and Q., which protects the hydroxyl group appropriately, is preferable. The condensate thus obtained contains 24-36 carbon atoms, and by subjecting it to a partial hydrogenation reaction, the acetylenic bonds are reduced to olefinic bonds, that is, the ω-hydroxy monomers are reduced to olefinic bonds. Unsaturated and Japanese fatty acids are obtained.

ω-hydroxy ow4-u obtained by the above method
The condensation reaction between s-monounsaturated fatty acids and essential fatty acids containing 11-24 carbon atoms in the molecule can be carried out, for example, in the form of a transesterification reaction using essential fatty acids in the form of acid anhydrides.

The esters thus obtained correspond to synthetic esters of essential fatty acids and ω-hydroxy fatty acids as defined above.

Next, some specific examples of preferred methods of synthesizing esters and derivatives thereof of the present invention will be described in detail.

The starting material in the synthesis of and 00-lylyl USt fatty acids can be ω-ethylenically unsaturated on fatty acids. This is first brominated according to the method described above, and then subjected to a dehydrobromination reaction to produce the corresponding ω-acetylenically unsaturated rofatty acid according to the reaction formula below.

The above acid (72) is treated differently according to the following two methods, namely, it is first brominated with potassium hypobromite to yield the bromide compound (73) of formula % (73) .

The second aspect is to convert the acid (72) into the corresponding ω-hydroxy acetylene compound using lithium aluminum hydride. This compound has the following formula (0::U((JHs)eOH (74)).

Then, between the zolomoic acid (73) and the ω-hydroxyacetylene compound (74) (Jadlot-Ohodkie
A wicz coupling reaction is carried out to produce diacetele/unsaturated ol-ω-hydroxycarzenic acid (75) of the following formula % formula % (75).

Complete elementaryization of this diacetylenically substituted compound (75) yields an ω-hydroquine fatty acid (76) having the following formula (%).

By reacting this with 4-toluenesulfonyl chloride, a tosyl derivative #(76) is obtained, and the latter adduct can be represented by the following formula. This tosyl derivative (77),
After condensation with the already described lithium-substituted ω-hydroquine acetylene compound (78) [the ω-hydroxyl structure of compound (78) should be excessively preserved], and then after removing the supporting group. , acetylenically unsaturated O3m-ω- and droxy fatty acid (79) are obtained, but this reaction is carried out by the following formula.
The above 2(go) is then concentrated in the presence of a catalyst (e.g. 4-dimethylaminopyridine) by working in ethyl acetate with a Lindlar catalyst in the presence of pyridine. Surplus lid anhydrous linole r
'It is safe to condense with M. This yields the desired Q-IJ luoyl (jsm fatty acid), and more specifically, liacontinic acid of the following formula: % (51).

1-0-benzoylsphingosine can advantageously be used as a starting material in the synthesis of ω-(0-lyluoyl)ceramide with 'J, Org.

It can be produced by the method described in Ohem, 46, 4: U93 (1981).

From this 1-0-benzoylsphingosine, the benzoyl group is first removed under the action of a base.

Bis-trimethylsilyl ether of sphingosine is then produced by reaction with trimethylsilyl chloride. ω-(O-rill oil) obtained by the above method
C■ Monoenoic acid (St) is transformed into the corresponding acyl chloride of formula (87).

By condensing acyl chloride (87) and bis-trimethylsilyl ether of sphingosine (86) and then performing a preservative group removal operation to remove the two trimethylsilyl ether radicals, ω-(0-lyluoyl)ceramide was obtained. , is resolved according to the following reaction formula.

+ 1 0101010 (OHI) HOH=OH (OH・Fist・■ 0)1. OH l]・0(OH wet) snow IUH=UH(OH,), 0-war 0 (1 ・self-〇(tlH goose) t (0H-(IH-(lH*)
t(0Us)nulls (88) Synthesis 1-0--<nzoylsphingosine can be advantageously used as the starting Im in the synthesis of the above ω-(0-lyluoyl)glucosylceramide; The 3-hydroxyl group is tertiary zotyldimethylsilyl chloride (TB
A tumor base is attached and protected by reaction with DMS-07). After removing the benzoyl group under the action of a base, by reaction with tetraresolinoylpromoglucose, 3-〇-tertiary zotyldimethylsilyltetraresolinoylglucosylsuphingosine of the formula % to be generated.

A condensation reaction between glucosylsphingosine (84) with a protective group and aylchloride (87) is carried out, and after removing the protective group, ω-(0-lyluoyl)glucosylceramide of formula 1 (57) is obtained. can get.

Synthesis of ω-(0-trihydroxylyleoyl)ceramide ω-(0-trihydroxylyleoyl)ceramide can be synthesized from linoleic acid. 6031-ω-hydroxy acid (80) in which linoleic acid is first converted to trihydroxyoctadecenoic acid and then to 9,10.13-tri-resolinoyloctadecene-11-oic acid. The transesterification reaction and the coupling reaction with the following formula (89) are carried out using an acyl chloride of the formula (87), and then the conjugated group is removed.
ω-(〇-trihydroxylyleoyl)ceramide of formula (5B) is obtained.

Continuing from page 1, Daikunin Masubashi Ima Muramoto Priority claim 9 June 16, 1982 ■ United Kingdom (GB
) ■ 8217414 ■ July 14, 1982 ■ United Kingdom 2 (GB) ■ 8220442 0 Inventor Udo Marius Thiodor Houtsmuller Vlaardingen Prince Bernhardlin, Netherlands 25 @ Inventor Diederich・Hentrik Neuteren, Rune Risdijk, Netherlands 4 0 Inventor: Hentrik Jakob Johannes Pavon, Netherlands Vlaardingen Louis de Colignylaan 0 Inventor: Colin Protty Merseyside, Lyrall, Heswall Burn, United Kingdom ston road 68

Claims (1)

[Claims] (1) If appropriate, a vehicle, a fragrance, and the following formula % formula % as an active ingredient (1) [where X is H-1c1-c10 alkyl, or the following formula % formula %] ( In the formula, R is HO-1c1-c4 alkoxy, polyhuman 90xyl alkoxy, N-sphingosyl and N-
(glycodylsphingosyl), a is an integer of 7-49, b is an integer of 10-98), and Y represents H-1 or the following formula (in the formula, 2 is -OH or epoxy oxygen; y is an integer from 26-36, or if 2 is an integer from 1-4 then y is 24-
is the residue of an all-cis n-6,9-fatty acid or a derivative thereof of A composition suitable for topical application to human skin, characterized in that it contains from o, ooi to 5 weight i% of at least one compound with an integer of -4. 2) The active ingredient has the following formula: The composition according to claim 1, characterized in that it is selected from ω-hydroxy-unsaturated fatty acids or their carboxy-substituted fatty acids, where f is an integer of 1-2. 3) The active ingredient is the following ω-human °roxy unsaturated fatty acid; ω-hyF roxy 6-cis dodecenoic acid (6) ω-hydroxy-21-cis-triacontinic acid
(7) ω-hydroxy-23-cis-
Triacontinic acid (8
) ω-human 90x-23-cis-todoacontinic acid
(9) ω-hydroxy-
25-cis-todriacontinic acid
(1(+1ω-human90x-25-cis-
Tetratriacontinic acid Q
Oω-hydroxy-41-cisubentacontenic acid
(4) The composition according to claim 2, characterized in that the active ingredient is a carboxy-substituted -ω having the above-mentioned formula.
-hydroxy fatty acid, with R being selected from -C-tetraalkoxy, polyhydroxyalkoxy, N-sphinzacil, and N-(glycodylsphingosyl) The composition according to item 2 within the scope of the invention. (5) The active ingredient is selected from hydroxy- or epoxy-wire conductors of essential fatty acids, or carboxy-substituted alkyl spindles thereof, having the following formula (%) (where 2 is an integer from 1 to 4): The composition according to claim hxx*'iy, characterized in that: (6) The hydroxy- or epoxy fatty conductor is 9.
10.13-) Lihydroxy-11-octadecenoic acid (31)9.12.
13-1-rehydroxy-10-oφ Tadecaceic acid (32) 9-Human 90x-10,12-octadecadienoic acid
(33) 13-hyProxy9.11-octadecashareic acid
(34) 15-hydroxy-5,8,11,13
-eicosatetraenoic acid (35)
11.12.15-1 Licht90x-5,8°13-
Eicosatrienoic acid (36)6.7,1
2.13-tetrahuman 90x-8゜10-octadecadienoic acid (37) 9-hydroxy-12
,13-oxide-10-octadecenoic acid
(38) 15-human 90x-11,12-
Oxide-5,8,13-eicosatrienoic acid (3
9) The composition according to claim 5, characterized in that the composition is selected from the following. (7) A composition according to claim 1, characterized in that the active ingredient is selected from esters having the formula: (8) The above ester has 30-34 carbon atoms ω-(O-
7. The composition according to claim 7, wherein the composition is a fatty acid (liluoyl) or a carboxy-substituted derivative thereof. (9) The ester is ω-(0-lyluoyl)-23-cis-todriacontinic acid (51) ω-(0-lyluoyl)-27-cis-todoriacontenoic acid
(52)ω-(O-columbinoyl)
-6-cis-suhite” acid
(53)ω-(arachito9noyl)-40-cis-antahcontenoic acid (54)ω
-(0-linoleoyl)ceramide” (55)
ω-(O-arachito9noyl)glucosylceramide

(56) ω-(O-liluoyl)glucosylceramide 9(57) ω-(9,10,13-1licht90xy-11-octadecenoyl)cerami)' (58)ω-
(O-9-human90xy-12,13-oxyY-1o
-octadecenoyl)-23-cis-todriacontinic acid (59)ω-(0-15-human9
0x-11,12-oxide"-5,8,13-eicosatrienoyl)ceramide
(6o)ω-(9,10,13)-trihuman9
0x-11-octadecenoyl)-23-cis-todriacontinic acid (61
)ω-(O-columpinoyl)-23-cis-todriacontinic acid (62)ω-(0
-columbinoyl)ceramide” (63)ω-(
O-γ-lilnoyl)-23-cis-todoacontinic acid (64) ω-(0-r-lilnoyl)ceramide (65) ω-(Q-arachitonoyl)
-27-cysuthitratriacontenoic acid
(66)ω-(O-arachitonoyl)ceramide
(67) Ethyl-9,10,13-1-licht90xy-11-octadecenoate (
68) The composition according to claim 8, wherein the composition is selected from the group consisting of: 68). a[Following formula %Formula % (1) [where X is the following formula (in the formula, a' is an integer of 27-33, b' is an integer of 50-64, R is HO-1C1-c4 is an unsaturated -ω-hydroxy fatty acid residue selected from alkoxy, polyhydroxyalkoxy, N-sphingosyl, ゛ and N-(glycodylsphingosyl), and Y is H-
1 or the following formula % formula % (wherein 2 is -OH or epoxy oxygen and X is 16-20
is an integer of 24-36, 2 is an integer of 01 or 1-4), or a residue of an all-cis n-6,9-fatty acid or a derivative thereof, where R is HO-1 or cl-c4 alkoxy, Y is -(!!-(CXHyZ2)CH3)] and has a purity of at least 10% by weight, a synthetic or purified fatty acid or Fatty acid ester compound. The following formula % formula % (70) of α (where d' is O or an integer from 1 to 24, and e'
is O or an integer from 1-24, d'+e' is an integer from 24-34, and f? 11. The compound according to claim 10, characterized in that it is an unsaturated fatty acid having t 1-2 (an integer of 1-2). The compound according to claim 11 which is 12ω-human90x-21-cis-triacontinic acid. The compound according to claim 11, which is 0→ ω-hydroxy-23-cysuto-9 triacontinic acid. The compound according to claim 11, which is aυ ω-human90x-25-cis-tetratriacontinic acid. (I7) The following formula % formula % (131 (where d is O or an integer from 1-46, e is 0 or an integer from 1-46, d+, is an integer from 4-46, and f is an integer from 1-2). −ω
- The compound according to claim 10, characterized in that it is a human 90 xy unsaturated fatty acid. (I mark) The compound according to claim 10, which is an ester having the following formula. The compound according to claim 18, which is 2(9ω-(O-lyluoyl)-27-cis-thitratriacontenoic acid. (2I) ω-(O-columbinoyl) )-6-cysuto-9decenoic acid.The compound according to claim 18, wherein (2<ω-(arachitriyl)-40-cis- is nt-acontenoic acid) Compound. (23) The compound according to claim 18, which is ω-(Q-IJ luoyl)ceramide. (24) Claim 18, which is ω-(O-arachito9noyl)glucosylceramide. The compound according to claim 18. The compound according to claim 18, which is (251ω-(0-lyluoyl)glucosylcerami F. (26) ω-(9,10,13-1-lihibiloxy-11-octadecenoyl) The compound according to claim 18, which is a ceramide. Compound according to Range 18. (28) ω-(0-15-human 10x-11,12-
The compound according to claim 18, which is C91ω-(9,10,13)-1-licht90x-11-octadecenoyl)-23- The compound according to claim 18, which is cis-todriacontinic acid. The compound according to claim 18, which is C30) ω-(O-columbinoyl)-23-cis-todriacontinic acid. Compound. The compound according to claim 18, which is C(1)ω-(O-columbinoyl)ceramide 9.
19. A compound according to claim 18 which is l-IJ acontenoic acid. 19. The compound according to claim 18, which is ω-(〇-γ-lilnoyl)ceramide 9. C34) ω-(O-arachitonoyl)-27-cis-tetra, triaconic acid Claim 1
Compound according to item 8. (G36) The compound according to claim 18, which is ω-(O-arachito9noyl)ceramide 9. A compound according to claim 18.