JP2716739B2 - Cosmetic composition having vasomotor action - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention comprises a polyunsaturated fatty acid, said polyunsaturated fatty acid being contained in the form of a complex with a natural or synthetic phospholipid, and a medicinal and cosmetic composition for topical administration It is about things.

The polyunsaturated acid which is the active ingredient of the composition provided by the present invention comprises ximenic or xymenic acid, γ-homolinolenic acid, docosahexaenoic acid, eicosapentaenoic acid and eicosahexaenoic acid.

Ximenic or xymenic acid is present in various plants, such as Ximenia africana and Santalum album .
On the other hand, the other three acids, especially Enocera biennis (Enotera)
hera biennis), Borago officinalis (Borago off)
It is well known that it is present in various animals or plants such as icinalis).

Eicosapentaenoic acid and eicosahexaenoic acid contained in fish oil have long been said to have valuable medicinal effects such as antithrombotic activity and anti-arteriosclerosis activity when administered orally or mixed with food and drink. well known.

Surprisingly, when the polyunsaturated acid is administered topically, it exerts vasomotor and vasodilatory effects, increasing the pulsatile activity in the arteries of the trunk and precapillary vessels and in the capillaries and venules. Was found to improve blood circulation.

Accordingly, the compositions of the present invention may be used in a variety of conditions to promote superficial circulation in the superficial or deep layers of skin or other tissues and improve skin health.

In particular, the compositions of the present invention have been found to be useful in the field of medicine for the topical skin treatment of sensory or organic peripheral vascular tissue, and in the field of cosmetics, are of natural origin [androgenic (androgenic) ) Hair loss] and hair loss due to pathological causes. Furthermore, it was found to be useful in treating impotence.

These applications include the United States, New York
Hack Pub.Co.'s “Remington's Pharmaceutical Science
in the form of creams, ointments, lotions, gels, etc., prepared in a conventional manner as described in the Handbook of the Invention, using appropriate excipients or binders.

The polyunsaturated fatty acid as the active ingredient can be used in a pure state or in a salt state, in an extract containing it, or in an ester state with glycerol.

According to an embodiment of the present invention, complexes of these acids with natural or synthetic phospholipids of the formula
The phospholipid used here is the following formula, (In the above formula, R and R ₁ may be the same or different and are mainly acyl residues in palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, and R ₂ is choline, ethanolamine or Which is a residue of serine).

For cosmetic applications, particularly preferred are those obtained from soy, bovine or porcine skin, liver or brain (similar to those found in human skin),
For other applications, it is preferred to use chemically homogeneous phospholipids whose structural units (acyl and phosphorylamino groups) are defined.

Such complexes are prepared by reacting an unsaturated fatty acid or an oil or extract containing it in an aprotic solvent with a phospholipid dissolved in a similar solvent. The phospholipid / fatty acid molar ratio is between 0.5 and 2, preferably about 1. After complete dissolution, the complex is recovered by removing the solvent under reduced pressure or by lyophilization or precipitation with a non-solvent.

The complex thus obtained is lipophilic, completely dissolved in a non-polar solvent and, when treated with water, provides a micellar fine dispersion which retains lipophilic properties. The structure of this complex is NMR
Analysis confirms that the polar portion of the phospholipid appears to be primarily responsible for complex formation.

As a matter of course, in the case of a phospholipid having a saturated acyl residue, the ¹ H-NMR signal characteristic of the hydrogen atom is not detected, and it can be seen that the band is broad due to the -N (Me) ₃ group.

In the case of the spectrum, the signal of the carbon atom of the complexed acid is characteristic of a choline or glycerin residue, whereas in the case of a ³¹ P-NMR spectrum, compared to the spectrum of the uncomplexed phospholipid. The phosphorus band has been shown to be broad.

Phospholipid complexes of fatty acids have advantages in terms of biocompatibility and activity by topical administration and can be conveniently obtained directly from plant extracts or oils containing said fatty acids.

The complex may be used alone, or may be finely dispersed in water and used as a micellar lipophilic aggregate, or may be used after being diluted with an oil conventionally used in medicinal and cosmetic compositions. good. It may also be mixed with other acids or miscible active ingredients and used as an oil / water or vice versa water / oil emulsion.

In preparing pharmaceutical and cosmetic compositions, the dosage that is considered to be biologically active can vary and is generally suitable for a concentration of about 0.1 to 10% by weight.

The results obtained by administering pure ximeninic acid or its triglycerides for topical use in the human body,
The results are shown in Table 1 below in comparison with placebo (olive oil) as a placebo containing no active ingredient.

Table 2 below shows the results obtained by complexing pure xymenic acid with soybean phospholipid.

These results were measured using thermography and plethysmography according to known procedures. Employs high-resolution liquid crystal contact thermography, which can detect ± 0.3-0.5 ° C changes in skin temperature, making it suitable for studying the sensory changes in blood circulation of skin capillaries. For this method,
Infrared blood volume meter (infrared photo-pulse plethysmography) is linked, thereby vasomotor activity (pulse + vasomotor activity) on small arteries and capillaries of the subpapillary network in very limited skin areas Activity) can be measured both qualitatively and quantitatively. In practice, the following method was used. Under basic untreated conditions, high-performance contact thermography (HPC) was performed on the temporal-cheekbone, cheek, and upper and outer thighs.
The measurement according to T) was performed. Thereafter, the test substance is applied to the skin (10 g of the test oil or extract 10 g on a skin area of 10 × 10 cm).
), And the measurement was performed.

Thereafter, the readings of the measurements were taken at regular time intervals (0 minutes,
15 minutes, 30 minutes, 45 minutes, 60 minutes or more).

At the same time, the readout head of the blood volume meter was applied to a well-defined skin area of the same specimen, and the plots were read at the same time intervals.

Ends of normal male and female subjects with sensory or organic circulatory disturbances of skin capillaries (Rainaud's disease, scleroderma) (such as fingertips, folds of the nails, roots of fingers, ridges of thumbs and little fingers) The motor activity of blood vessels was measured.

In total, 20 subjects with an average age of 46 ± 4.2 were treated. As a result, when an oily extract of Ximenia africana, a complex with ximenic acid, and its corresponding phospholipid, was applied to the skin of the subject, the vasomotion of the arterioles of the skin was substantially enhanced, and as a result, It was confirmed by thermographs and thermometers that the previously closed capillaries were opened, without increasing erythema or flushing of the skin, increasing the speed and volume of blood circulation and increasing the local skin temperature. The time period during which the local capillary blood circulation is improved by the present invention is much longer than when a conventionally known vasoactive agent is applied to the skin.

The xymenic acid and other polyunsaturated fatty acids and various derivatives thereof of the present invention have also been found to be effective in treating scalp suffering from alopecia or abnormal hair loss due to impaired blood circulation in the hair follicles.

In the tests, the same method was used except that air bed high performance contact thermography (HPCT) was employed. In this way, a thermographic map of the surface of a convex portion such as the brain, the calvaria, etc. can be obtained with high resolution. In total, treatment of 22 subjects recorded an increase in head skin temperature and an increase in arterio-arteriole pulse activity.

Therefore, this data can be applied to other skin tissues of the human body. Thus, ximenic acid, other unsaturated acids and derivatives thereof can be used in the treatment of alopecia, or conditions associated therewith, requiring the use of vasodilators and vasomotor actives, to stop hair loss, Stimulates hair growth. Also, if the hair is strengthened and treated with, for example, xymenic acid / phospholipid complex after normal head washing, combing becomes better and the hair becomes supple, and at the same time, seborrhea and dandruff symptoms sometimes occur. Significant improvement. As such, the compositions of the present invention are particularly efficacious in treating persons suffering from hair loss.

Furthermore, the compositions of the present invention are also effective in the topical treatment of impotentia erigendi due to vascular disorders, and when applied to the penis, erect quickly and maintain a satisfactory time.

The present invention is illustrated in more detail by the following examples, but the present invention is not limited thereto.

Production Example 1 Production of xymenic acid triglyceride from Ximenia africana oil 50 g of an oil obtained by extracting xymenia africana berries with hexane was previously prepared with cyclohexane /
600 g of silica gel stabilized with a 95/5 mixture of ethyl acetate
The column was chromatographed and eluted with the same solvent mixture.

An intermediate polarity fraction containing the single compound, the most abundant component in the extract, was collected. After evaporation of the solvent, the residue was dried under vacuum at 50 ° C. overnight to give 18 g of a pale yellow oil. As a result of mass spectrometry, the product had a molecular weight of 872 and corresponded to xymenic acid triglyceride.

Production Example 2 Production of Complex of Ximenynic Acid and Distearoylphosphatidylcholine 2.8 g of Ximenynic acid was dissolved together with 15.5 g of synthetic distearoylphosphatidylcholine (99%) in 50 ml of anhydrous methylene chloride.

The starting suspension thus obtained is heated to a gentle reflux and completely dissolved, the solvent is removed under vacuum,
The remaining solid residue was dried at 40 ° C. under vacuum overnight. The resulting white solid had a melting point of 120 ° C., and the ¹ H-NMR analysis in deuterated chloroform (CDCl ₃ ) showed that a proton signal based on the double bond of xymenic acid was found. Although not, the signal reappeared after the addition of dimethyl sulfoxide (DMSO) or other high-dielectric solvent to disrupt such compounds.

Production Example 3 Production of complex of xymenic acid and soybean phospholipid 2.78 g of ximenic acid was converted to 15.3 g of soybean phosphatidylcholine
Together with 50 ml of anhydrous methylene chloride. The mixture was left for 2 hours, the solvent was removed at 40 ° C. under vacuum and the product was dried at 40 ° C. overnight. As a result, the yellow product 17
g was obtained, which had a melting point of 55 ° C.

Production Example 4 Production of Complex of γ-Homolinolenic Acid and Distearoylphosphatidylcholine 2.78 g of γ-homolinolenic acid was dissolved together with 15.76 g of distearoylphosphatidylcholine in 100 ml of anhydrous dioxane. The resulting solution was kept at room temperature for 2 hours and then lyophilized. As a result, 18 g of a white powder was obtained, which was found to have more complex properties by spectroscopic analysis.

 Some composition examples of the composition of the present invention are shown below.

Composition Example 1 Composition in 100 g of cream cream Ximenynic acid 5 g Isopropyl myristate 5 g Wheat germ oil 2.5 g (Wheat germ oil) Ethyl alcohol 1.5 g Imidazolidinyl urea 0.3 g Methyl hydroxybenzoate (preservative) 0.1 g Polysorbate 80 2 g (polyoxyethylene fatty acid esters) carboxyvinyl polymer 1 g of sodium hydroxide (10%) 2 g flavor composition (essence) 0.1 g purified water 80.5g composition example 2 gel compositions gel in 100g ximenynic acid complex 2.5g Sofuchigen ( Softigen) 767 25 g (C ₈ -C ₁₂ ethoxylated triglyceride) Volpo 207 g (polyoxyethylene 20 oleyl ether) imidazolidinyl urea 0.3 g methyl p-hydroxybenzoate 0.1 g Flavoring composition (essence) 0.1 g carboxy Vinyl polymer 1.5 g Triethanolamine 2 g Purification Water 61.5g Composition Example 3 Gel Gel Composition 60% A eicosapentaenoic acid in 100 g 1.0 g Ximenynic acid 2.5g Borupo (Volpo) 20 7.5 g (Polyoxyethylene 20 oleyl ether) polypropylene glycol 20 g Sofuchigen (Softigen) 767 20 g ( C ₈ -C ₁₂ ethoxylated triglyceride) Carboxyvinyl polymer 1.5 g Triethanolamine 2 g Imidazolidinyl urea 0.3 g Methyl p-hydroxybenzoate 0.1 g Perfume composition (essence) 0.1 g Purified water 44 g

Continuation of front page (56) References JP-A-61-171419 (JP, A) JP-A-62-96422 (JP, A) JP-A-61-207330 (JP, A) JP-A-61-23699 (JP, A) , A) Prostaglandins, 1987, Vol. 33, No. 3, pp. 403-417 Biochemica et Biophysica Acta, 1987, Vol. 921, pp. 621-624 Rivita Italiana E.C. P. P. O. S, 1979, LXI-n. 5, pp. 190−193

Claims (9)

(57) [Claims] An active ingredient comprising one or more polyunsaturated fatty acids selected from the group consisting of xymenic acid, γ-homolinolenic acid, eicosapentaenoic acid, eicosahexaenoic acid and docosahexaenoic acid, as a phospholipid. A cosmetic composition which is contained in the form of a complex of the above and is mixed with an excipient. 2. An active ingredient represented by the formula: (In the above formula, R and R ₁ may be the same or different and are mainly acyl residues in palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, and R ₂ is choline, ethanolamine or The composition according to claim 1, which comprises a complex of a phospholipid represented by the formula: and a complex of xymenic acid, γ-homolinolenic acid, eicosapentaenoic acid, eicosahexaenoic acid, or docosahexaenoic acid. 3. The composition according to claim 1, wherein the polyunsaturated fatty acid is xymenic acid. 4. The composition according to claim 1, comprising 0.1 to 10% by weight of the active ingredient. 5. The composition according to claim 1, wherein the composition is a cream, a gel, a lotion,
5. The composition according to claim 1, which is in the form of an ointment. 6. A polyunsaturated fatty acid selected from the group consisting of xymenic acid, γ-homolinolenic acid, eicosapentaenoic acid, eicosahexaenoic acid and docosahexaenoic acid, and a compound represented by the formula: (In the above formula, R and R ₁ may be the same or different and are mainly acyl residues in palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, and R ₂ is choline, ethanolamine or Which is a residue of serine). 7. The ratio of phospholipid / polyunsaturated fatty acid is 0.5 to 0.5.
7. The complex according to claim 6, which is 2. 8. The complex according to claim 6, wherein the phospholipid is soy lecithin. 9. The complex according to claim 6, wherein the polyunsaturated fatty acid is xymenic acid.