AU631441B2 - Creación de Inventos y Patentes con Inteligencia Artificial

AU631441B2 – Preparations for topical use containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face and some skin areas of the body
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AU631441B2 – Preparations for topical use containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face and some skin areas of the body
– Google Patents
Preparations for topical use containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face and some skin areas of the body

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Publication number
AU631441B2

AU631441B2
AU59169/90A
AU5916990A
AU631441B2
AU 631441 B2
AU631441 B2
AU 631441B2
AU 59169/90 A
AU59169/90 A
AU 59169/90A
AU 5916990 A
AU5916990 A
AU 5916990A
AU 631441 B2
AU631441 B2
AU 631441B2
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AU
Australia
Prior art keywords
deoxyribonucleic acids
skin
depolymerized
defects
effective amount
Prior art date
1989-09-07
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AU59169/90A
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AU5916990A
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Inventor
Giovanni Gazzani
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Crinos Industria Farmacobiologica SpA

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Crinos Industria Farmacobiologica SpA
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1989-09-07
Filing date
1990-07-20
Publication date
1992-11-26

1990-07-20
Application filed by Crinos Industria Farmacobiologica SpA
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Crinos Industria Farmacobiologica SpA

1991-03-14
Publication of AU5916990A
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patent/AU5916990A/en

1992-11-26
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1992-11-26
Publication of AU631441B2
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patent/AU631441B2/en

2010-07-20
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Classifications

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES

A61K31/00—Medicinal preparations containing organic active ingredients

A61K31/70—Carbohydrates; Sugars; Derivatives thereof

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES

A61K31/00—Medicinal preparations containing organic active ingredients

A61K31/70—Carbohydrates; Sugars; Derivatives thereof

A61K31/7088—Compounds having three or more nucleosides or nucleotides

A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2′-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3′-5′ phosphodiester links

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES

A61K8/00—Cosmetics or similar toiletry preparations

A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition

A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds

A61K8/60—Sugars; Derivatives thereof

A61K8/606—Nucleosides; Nucleotides; Nucleic acids

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P17/00—Drugs for dermatological disorders

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P9/00—Drugs for disorders of the cardiovascular system

A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

A61Q19/00—Preparations for care of the skin

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

A61Q19/00—Preparations for care of the skin

A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

A—HUMAN NECESSITIES

A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE

A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

A61Q19/00—Preparations for care of the skin

A61Q19/06—Preparations for care of the skin for countering cellulitis

Abstract

Compositions for topical use containing as active ingredients depolymerized deoxyribonucleic acids can be used for the reduction of the unaesthetisms of the face skin, due to the couperose. Said compositions can be advantageously used also to locally reduce, in the lower limbs, the skin unaesthetisms (dilated capillaries, oedemas, tumefactions), resulting from a situation of an extended physical stress acting on the above-mentioned legs.

Description

II~ COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952 COMPLETE SPECIFICATION NAME ADDRESS OF APPLICANT: W%13 4418 Crinos Industria Farmacobiologica S.p.A.
Piazza XX Settembre, 2 22079 Villa Guardia (Como) Italy
I
o 0 NAME(S) OF INVENTOR(S): Giovanni GAZZANI ADDRESS FOR SERVICE: DAVIES COLLISON Patent Attorneys 1 Little Collins Street, Melbourne, 3000.
COMPLETE SPECIFICATION FOR THE INVENTION ENTITLED: Preparations for topical use containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face and some skin areas of the body The following statement is a full description of this nvention, including the best method of performing it known to me/us:- 0 000s 0* 0 0* 0&
DESCRIPTION
This invention has as its first object the topical use of formulations containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face caused by «couperose» I A further object of the invention relates to the topical use of said formulations to reduce vhe unsightly defects which occur in some areas of the skin in the lower limbs attributable to a situation of prolonged fatigue of the S limb, as for example may occur in subjects who in carrying out their respective activities have to stand for long S periods of time.
In cases of this type, abnormally dilated capillaries, associated with oedemas, tumefactions etc., may appear locally on the skin of the legs and ankles.
In other cutaneous areas, the epidermis of the limb may instead appear livid and discoloured.
In these conditions, in the area of the limb affected by the abovementioned phenomena, there may also be a sensation of aching and/or heaviness. The active ingredients of the formulations in question, that is to say deoxyribonucleic acids of low molecular weight, are prepared by known depolymerization procedures. More particularly, said active ingredients are preferably obtained on the basis of the technique which forms the object of the USA patent no.
3.899.481.
•a I II i i The relative chemical and chemico-physical properties of the depolymerized deoxyribonucleic acids which are obtained according to this procedure are given in Table I. The analytical methods used to determine the relevant parameters have already been referred to in the previous European patent application no. 88.115.824, regarding the cosmetic use of the aforementioned substances as tricogen factors, to which therefore reference is made.
Prior to relating the experiments which have demonstrated the efficacy of the formulations containing depolymerized deoxyribonucleic acids in the uses provided for by this invention, it must be explained here what is meant by the term «couperose», since in the literature of the field it has been used in different ways according to the presence and contextual prominence on the skin of certain eatures with which it may appear.
Dermatological tests define this skin affection more er +ros)s correctly as kte angiect c. since couperose gives rise to a reddening, widespread to a greater or lesser extent, of the epidermis of the face, in which dilated surface blood vessels are prominent (telangiectasis) It must be pointed out here that the aforementioned reddening may be widespread over the whole face, or localised in certain zones, such as on the cheekbones, nose S or under the eyes. The aforementioned telangiectasis, which accompanies, as we have seen, the reddening of the face, may at times take on characteristic shapes known as, according to the cases, «star», «stripe», «plume».
.0 As regards the experiments which proved the feasibility of S the topical use of the aforementioned formulations to reduce «couperose» and the defects of the cutaneous areas of the lower limbs, it should be noted that the main common cause of said phenomena is clearly to be found in a modification of the normal conditions of the surface vessels, more particularly regarding their mechanical resistance characteristics.
.In this respect mention should be made first of all of an experiment on animals (rats), in which blood capillary resistance was lowered by administering a special diet, but S nevertheless, following repeated topical applications of formulations containing depolymerized nucleic acids, demonstrated at the end of treatment a considerable increase in the capillary resistance values compared to the original state. The trial was performed on 55 animals, divided into 6 groups as shown in Table II and then treated with the formulations given in Table III. Table IV illustrates the analytical properties of the deoxyribonucleic acids which go to make up the compositions described in the aforementioned Table III.
It should be noted that in all cases the aforementioned formulations contained, as active ingredient, an equal-weight mixture of the batches given in Table IV.
of the 6 aforementioned groups were fed with a diet laoking in vitamin P (Charlier diet, commercially «2 2 available), which in time gives rise to a consistent reduction in thz mechanical resistance of the blood vessels Rialdi: «Determinazione della resistenza capillare durante trattomento percutaneo con sostanze cheratoplastiche dotate di attivita’ anticouperosica» Riv. It. EPPOS 422-d2S 19?8).
Capillary resistance was determined on each occasion occordirg to the Lavollay technique Lavollay et al.
«Problems posed by activity of certain flavonoids on vascular resistance» in «Pharmacology of plant phenolics», Symposium Oxford, 1958, Proceedings pages 103-122, 1959).
In order to perform the required determination on the basis of the technique in question, the skin of the dorsolumbar region was shaved thoroughly and slightly smeared with vaseline oil. The zone suitable for determination was an area of circa 2 x 1.5 cm, extending in length from the last ribs and bordering in width the paravertebral fasciae.
The animals were slightly anaesthetised and then, on the dorsal region mentioned previously, the instrument for measuring capillary resistance was applied, consisting of a suction cap attached to a vacuum pump (petecchiometer, Ealdinelli, Milan) The apparatus therefore enables the value of the depression, S expressed in mm Hg, capable of causing breakage of the blood S vessels, to be determined.
Said determination was performed on all the groups of *ft animals, fed with the Charlier diet, on the 21st day from S* the start of the experiment. It was ascertained that in all S. the groups the animals presented a statistically significant reduction in capillary resistance compared to the control group, which had instead been fed with a normal diet (MIL Moiini diet).
Said reduction was moreover statistically significant in the various groups. The absolute value of capillary resistance of the treated animals was between 163.3 (Group U) and 183.0 (Group in the untreatec animals (control group) it was 319.6 mm Hg.
Topical treatment was begun on the 22nd day and continued for 7 consecutive days. The cutaneous zone of the animal, on which the formulations in Table III were applied, was the same on which determination of capillary resistance according to the Lavollay technique had previously been performed.
The administrations were repeated three times a day applying topically 0.2 rhl at a time of each of the aforementioned formulations or 0.2 ml of physiological solution (control group), At the end of the treatment period the capillary resistance was again measured using the same technique. The results are given in Table V.
As can be seen therefore, topical application of depolymerized deoxyribonucleic acids by means of the formulations given in Table III and operating according to the experimental design illustrated above, all the doses 3 r.
I
tested gave rise to a statistically significant increase in capillary resistance. Table IV moreover shows that the preparation containing S% concentration of depolymerized deoxyribonucleic acids (group E) caused, in the treated rats, an increase in capillary resistance to a value relatively close to that of the control group. Also worthy of note ij the fact that the commercial preparation containing O-(p-hydroxyethyl)-rutosidea as active principle, proved more or less as effective as the gel containing the depolymerized nucleic acids at 1.25% concentration.
TABLE I Analytical chemical and chemico-physical parameters of the depolymerized deoxyribonucleic acids which can be used for thq objects provided for by this invention.
4. 4.
*o 4 4.
4 6 46 4 Phosphorous Nitrogen Deoxyribose Adenine Cuanine Cytosine Tymine A G T C r+C 8.0 -9.6 13.0 15.0 17.0 -24.0 8.0 11.0 7.0 5.5 8.0 11.0 i 4 4r9 6
Q
-Molecular weight 1 Preferably 1 these data refer to weight of the dry product.
0,000 100,000 5,000 60,000 the corresponding percentages in 0.87 1.01 4 TABLE II Capillary fragility induced in animals by administration of the Charlier diet. Groups, number of animals per group dnd relative treatment.
Group No. of animals Treatment A 10 normal diet, topical treatment with physiological solution (control group).
8 10 Charlier diet, topical treatment with placebo formulation (Table III).
C 10 Charlier diet, topical treatment with gel at 1.25% concentration (Table
III).
D 10 Charlier diet, topical treatment with gel at concentration (Table
III).
E 10 Charlier diet, topical treatment with gel at concentration (Table
III).
F 5 Charlier diet, topical treatment with a commercial preparation containing 2 g 0 -hydroxyethyl)rutosidea, 600 mg e» polymerized acrylic acid, 50 mg disodium ethylenediaminetetreacetic acid, mg benzalkonium chloride, bidistilled water q.s. to 100 g.
r TABLE III CL)nposi tion of the cosmetic for’mulat ions o? Capi Illary f racgilIit y Components per 1oLg Placebo 1.2S% of’ gel depolymerized deoxyribonucleic–12 acids g 912 Car’bopol 940 g 2.0 2.0 Dihydroxypropane g 4.04.
eenzyl alcohol g 1.4 1.4 Dimethyl carbonol g 2.0 2.0 EOTA g 0.05 0.05 Methyl-phydroxyben’.oate g 0. 15 0.15 Propyl-phydvoxybenzoate g 0.03 0.03 20% w/v NaOh g 4.0 4.0 Distill. H 2 0 q.s. to g 100 100 used in texperiment3 2 .5% 2.5 2.0 4.0 1.4 2.0 0 .05 0.15s 0.03 4.0 100 s G% 1.4 0. 0.1is U. 03 1 00 9@ *4 9 9* ‘0 4 **39*s* 9 4 9 S. 9 9.
4 4 5 4 0 *9S* 4**9 4.
99 0 9.
4 949 S. P 0 .9.4 0* 0 4* .9 -6 rABLE IV Chemical and chemico-physical depolymeri zed deoxyribonucleic for’muldtions set out in Table IIl.
analytical parameters Ba t ch Phosphorus +)8.62 Deoxyribose U)19.0 Adenine +)10.0 Guanine C .)9.3 Cytosine .0 rhymine 10.5 prop er-tie s acids used the th e B a t ch 8. 25 20.4 10. 1 8.5 6.8 9.7? Batch C 8 22.3 9.6 8.4 9.4 4s44 #4 4 4 4**q 4* 4 440* .4
I
*4 4 4 A +G T +C Molecular weight the data refer to the weight of the dry product.
0.93 0 .97? 0 29,000 18,000 43,000 corresponding percentages in 44.4 *9*4 4S 0 @4*4 4 44 4.
*4 7rABLE V Results relating to the effect of topical applications of preparations containing as active ingredients nucleic acids with the properties given in Table I, on rats in which surface capillary fragility was induced experimentally by administration of the Charlier diet for 21 days prior to the start of the trial. The applications were continued for 7 consecutive days, determining capillary rosistance according to the Lavollay technique, before beginning topical applications and at the end of treatment. The results below are expressed in mm Hg (Mean S.E.) GROUP C 4) (Ref. Tab. II) A 319. 6 6.7 320.6 9.2 1.0 S.0 0.3 8 163.3 3.6 169.0 5.5 5.7 5.9 3 r C 166.5 6.5 17S,0 14.4 8.5 14.0 D0 169.8 6.4 212.5. 11.0* 42.7 11.5** 2S s o E 172.8 5,2 237.5 64.7 5. 37 F 183.0 11.9 2??77.0 10 94.0 12.7** 51 G 172.0 5.0 209.0 14.2** 37.0 22 C1) Capillary resistance before start (zero time) Capillary resistance at end of trial Difference vs. zero time *9 variation vs. zero time p 0.05 p 0.01 Student’s t-test vs. zero time As confirmation of what was said previously regarding the :0 common origin of the defects of the epidermis treated here, a, as regards «couperose» it should be noted that literature S Curri et al. «sostanze nattrali ad azione sul microcirculo cutaneo» La Medicina Estetica Year 4 no. 1 January/Marci 1980) also demonstrates that capillary fragility is an important factor in the genesis of this particular phenomenon.
The efficacy of depolymerized deoxyribonucleic acids in reducing «couperose» on the face has been demonstrated with a test performed on 10 female subjects, aged between 13 and 8 I- -Y il 59 years (average age 34 years). Subjects with phlogistic lesions of the face and those undergoing treatment with drugs ingested by the systemic route were excluded from the trial.
During experiments the formulation in example 2 was used.
The ,ative ingredient consisted of an equal-weight mixture of the batches of depolymerized nucleic acids given in Table IV. The applications were performed twice a day and were repeated for 60 consecutive days. Investigations were performed before the start and at the end of the experiments, by slide photographs, taken in standardised lighting conditions and using a macro lens, maintaining the focal length and the shutter opening constant. The photographs were taken in the morning, with the patient previously resting for twenty minutes in a room with controlled temperature and humidity.
The intensity of the colour of the epidermis revealed by the slide was then processed by means of a device for measuring colour intensity (Minolta Chroma Meter chromometer), set to measure the a* hemivector (chromometric coordinate drawn up by the International Lighting Commission in 1976), corresponding to the green-red spectrum.
In this way it was possible to estimate the quantity of ‘ed in the erythema.
In addition to the aforementioned instrumental parameter, a subjective evaluation of the evidence of reddening and the o 1 presence of dilated capillaries was also carried out on the basis of a score with the following points score system: 3 highly evident, 2 averagely evident, 1 slightly evident.
Table VI below gives the results obtained.
In order to further clarify the significance of the reduction in the a* parameter which was established at the end of the trial following treatment with the formulation containing the aforementioned depolymerized nucleic acids, S it should be mentioned that the same parameter, determined out of a population of 91 healthy subjects, was 13.00. On the basis of Table VI, it can therefore be concluded that in this trial topical treatment with the aforementioned preparations gave rise to a significant improvement in the S* conditions of patients’ faces.
*0 e ea 9- I I FABLE VI Reduction in «couperose» on the face due to the effect of topical applications of formulations containing depolymerized nucleic acids, repeated twice a day for d-ys. The values shown refer to the a* parameter and to the subjective evaluation of the reduction in «couperose» by means of the corresponding score. The determinations (Mean were made before the start of treatment and after days.
Parameter Zero Time After 60 days a* 19. 1 0.36 15.96 0.45 Subj. eval. 2.50 0. 1 1.70 0.15 (score) P 0.01 Student’s t-test rhe efficacy of the preparations containing depolymerized nucleic acids in reducing cutaneous phenomena on the lower limbs as result of conditions of prolonged local fatigue, was demonstrated in a trial conducted on 30 female subjects, aged between 30 and 50 years (average age 40 years). All these subjects presented oedemas at the ankles with very co evident and dilated surface capillaries on the lower limbs In all the cases examined, these phenomena were accompanied by an aching and/or heavy sensation in the area of the limb concerned.
Treatment lasted 60 days. The daily topical application was S performed on the whole limb. The composition of the formulation used in this trial is given in example 4. The active ingredient of the cream was composed of an equal-weight mixture of the three batches set out in Table
IV.
The following parameters were evaluated before the start, at 30 and 60 days: subjective parameters: sense of heaviness objective parameters: oedemas at the ankles, presence of possible areas of skin pallour.
The evaluation of these subjective and objective parameters was performed by means of the score method, awarding a value, In arbitrary units, to the evidence of the phenomenon on the basis of the following scale: 0 absent, 1 slight, 2 moderate, 3 strong, 4 very intense.
At zero time an.d at the end of the trial a capilleroscopic investigation of the ankle (lower third of leg, regio cruris medialis 5 cm above the internal malleolus) was performed using a Wild-MS-C instrument connected to a camera.
Study of the various photographs concerned the diameter of the capillaries and the number of loops and the presence of possible microhaemorrhages. The extent of these findings was evaluated by means of the score method awarding a value from 1 to 4, according to the following scale: 1 worsened, 2 original state, 3 improved, 4 much improved.
10 Measurement of the parameters described above was performed in the afternoon, so that the aforementioned cutaneous phenomena appeared with the normal evidence.
The results are give in Tables VII and VIII below.
TABLE VII Value of the scores relating to the following clinical parameters: oedema, sensation of heaviness, areas of skin pallour, measured at zero time and after 30 and 60 days respectively (Mean Parameter Zero Time 30 days 60 days Oedema 0.9 0.2 0.4 0.1* 0.3 0.1* Heaviness 2.5 0.1 1.3 0.1* 0.7 0.2* skin pallour 0.8 0.2 0.5 0.1* 0.3 0.1* p 0.01 S» TABLE VIII Modification in the amount of the average values of the scores relative to the overall evaluation of the S capillaroscopic examination at zero time and after 60 days (Mean S.0.) *4 Parameter Zero time 60 days capillaroscopic analysis (scores) 2.0 0.0 3.1 0.1* p 0.01 Tables VII and VIII show that at the end of the trial the improvement obtained following repeated topical applications Sof the above formulation, was statistically significant for all the parameters considered. It should be noted here, with reference to the capillaroscopic examination, that at the end of treatment the surface capillaries had almost disappeared, or at any rate had faded greatly, from the epidermis. The areas with oedema were fully resolved.
Example 1 Procedure for obtaining depolymerized deoxyribonucleic acids from a DNA of high molecular weight.
1 kg of DNA extracted from entrails is dissolved in 200 litres of deionised water at 70 0 C in which 27 kg of trihydrate sodium acetate and 30 kg of glacial acetic acid had previously also been dissolved. The solution is then heated at 700C for 4 hours. Subsequently it is brought to 11
S
neutrdl pH with NaIJH 5 N It is then f iltered obtaining 220 litres of solution. The depolymerized deoxyribonucleic acids are then precipitated by adding 24 litres of methanol 1 I p art s of solvent/i part of solution). The precipitate is processed according to normal techniques, obtaining c irce 660 g of product, The analytical data rp-iative to this preparation are th e following data in percentage of the dry product) Phosphorous 8.74, Deoxy -ibose 18.3, Adenine 9.4, Guanine 7.8, Cytosine 7.2, Thymine 9.5, A G T C 0.88, molecular weight 68,000.
Example 2 ANTI-COUPEROSE CREAM Depolymerized deoxyribonucleic acids Propylene glycol Tween 60 Span 60 0 lyceryl monostearate Ifsopropyl myristate Perfume and preservatives Demineralized water 3 2 S F.
4.5 g 3 8a 5 2 q~s q .s to 100 too* 0 of 4 *0GG0 06 Example 3 ANTI-CELLULITE CI EAM Depolymerized deoxyribonucleic acids Polyethylene glycol stearate Cetyl alcohol Propylene glyco! Decyl oleate Perfume and preservatives Demineral,1zed water, 3 9 9 S g 10 g q..
q’s. to 100 g Example 4 LEG CREAM Depolymerized deoxyribonucleic acids Ethoxylated fatty alcohols Ace togl1y oe ry 1 Sorbitol Bee swax Perfume and preservatives Demineral ized water 3.5 g 7 g 4 2 q .s.
q ,s to 100 2 12 a up..
Example S EYE CONTOUR CRLAM Depolymerized nucleic acids Car’bopol. 940 Sodium hydrate (;Iyce rine Perfume and preservatives Demineraliz~d water Example 6 LOTION FOR ASPHYTIC SKIN 4 2 1 S g 0.7 g .9 q S.
q -s to 100 g Gepolymerized deoxyribonucleic acids G 1y ce r in e N M, Perfume andi preservatives Oemineralized water 4 g q S.
q .s to 100 g esee
C
~k C 4 4.
4 4 44W* ‘ewe..
4 494W
C,
44 4 4 4e
C
CCe 4 Example 7 SOOTHING OINTMENT Depolymerized deoxyribonuol eio acids W/O self-emulsifier base Almond oil Propylene -‘yool Perfume ano preservatives Oemineral ized woter 3 g 20 g 5 g S g q s.
q.s. to 100 g SeWS 4 444W *eve e WC 4 4* .4 9 Ci.
C 4* CC 4 4 4.
.t 13-

Claims (2)

1. A method of reducing the unsightly defects of the epidermis of the face caused by couperose as herein before defined and/or to locally reduce, on the skin of the legs and ankles the defects which appear collaterally to a prolongued fatigue of lower limbs in an animal in need thereof, comprising the step of administering topically to said animal an effective amount of depolymerized deoxyribonucleic acids having the following analytical properties, expressed as percentage in weight of the dry product V* S S. Phosphorous Nitrogen Desoxyribose Adenine Guanine Cytosine Ihymine 8,0 13,0 17,0 8,0 7,0 5,5 8,0 9,6 15,0 24,0 11,0 11,0 1,01 100,000 )le vehicles and/or Adenina Guanina Thymine Cytosine Molecular Weight dalton units 8,87

10.000 tcgether with one or more cosmetically suitat excipients. 2. A method according to claim 1 wherein said animal is a human. 3. A method according to claims 1-2, characterized in that said deoolymerized deoxyribonucleic acids have a molecular weight of preferably between 15.000 an 60.000. 4. A method according to claims 1-3, characterized in that said effective amount of depolymerized deoxyribonucleic acids, expressed as percentage by weight of the composition, is between and 5 A method according to claim 4, characterized in that said effective amount of depolymerized deoxyribonucleic acids, expressed as percentage by weight of the composition, is between 1 and 4%. 6. A method according to anyone of the preceding claims characterized in that the compositions containing said effective amount of depolymerized deoxyribonucleic acids are in the form of creams, gels, ointments. i 7. A method according to anyone of the preceding claims 1-6 for reducing unsightly defects of the skin and the body caused by «coLperose» as hereinbefore defined. 8. A method according to any of the preceding claims 1-6 for reducing locally, on the skin of the legs and ankles, the unsightly defects which appear collaterally to prolonged fatigue of the lower limbs. 9. A composition when used in accordance with claim 1, substantially as hereinbefore described with reference to the examples. DATED this 25th day of September, 1992. CRINOS INDUSTRIA FARMACOBOTLOGICA S.P.A. By its Patent Attorneys S*COLLISON CAVE DAVIES COLLISON CAVE .e ,.c 920925,mgbdat.01259169-90.U,15

AU59169/90A
1989-09-07
1990-07-20
Preparations for topical use containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face and some skin areas of the body

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IT8921650A

IT1232318B
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1989-09-07
1989-09-07

TOPICAL COMPOSITIONS CONTAINING DEPOLYMERATED NUCLEIC ACIDS FOR SKIN AND BODY COSMETICS.

IT21650/89

1989-09-07

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Preparations for topical use containing depolymerized deoxyribonucleic acids to reduce unsightly defects of the epidermis of the face and some skin areas of the body

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IT1232318B
(en)

LU
(1)

LU87799A1
(en)

NZ
(1)

NZ233987A
(en)

PT
(1)

PT95211B
(en)

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Priority date
Publication date
Assignee
Title

IT1252174B
(en)

1991-12-09
1995-06-05
Crinos Industria Farmaco

OLIGODESOXYBONUCLEOTIDES WITH ANTI-SCHEMICAL ACTIVITY AND PROCEDURES FOR THEIR OBTAINING

AU6714094A
(en)

1993-04-28
1994-11-21
Ribozyme Pharmaceuticals, Inc.
Ocular delivery of nucleic acid

US5470577A
(en)

1993-07-07
1995-11-28
Trustees Of Boston University
Stimulation of tanning by DNA fragments or single-stranded DNA

JP2688116B2
(en)

1993-07-29
1997-12-08
ロレアル

Make-up composition

IT1270602B
(en)

1994-07-12
1997-05-07
Indena Spa

ESCULOSIDE BASED FORMULATIONS AND THEIR USE IN THE PHARMACEUTICAL AND COSMETIC FIELD

US5858339A
(en)

1995-03-29
1999-01-12
L’oreal
Method for making up the eyes using deoxyribonucleic acid

DE19545107A1
(en)

1995-12-04
1997-06-05
Beiersdorf Ag
Use of adenosine

USRE37380E1
(en)

1996-07-12
2001-09-18
Bertrand Piot
Method for making up the eyes using deoxyribonucleic acid

DE19815090A1
(en)

1998-04-06
1999-10-14
Henkel Kgaa

Cosmetic products

US6946144B1
(en)

1998-07-08
2005-09-20
Oryxe
Transdermal delivery system

CA2365901A1
(en)

1999-04-14
2000-10-19
Musc Foundation For Research Development
Tissue-specific and pathogen-specific toxic agents and ribozymes

WO2004002416A2
(en)

2002-06-26
2004-01-08
The Penn State Research Foundation
Methods and materials for treating human papillomavirus infections

JP5025253B2
(en)

2006-03-31
2012-09-12
日生バイオ株式会社

Formulation for basic cosmetics and basic cosmetics

US9358037B2
(en)

2007-06-26
2016-06-07
Roxwood Medical, Inc.
Method and apparatus for centering a microcatheter within a vasculature

KR20180053318A
(en)

2015-09-17
2018-05-21
제이알엑스 바이오테크놀로지, 인코포레이티드

Approaches to improve skin hydration or moisturization

GB201703656D0
(en)

2017-03-07
2017-04-19
Univ Sheffield
Wound healing medicament

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* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

FR1361925A
(en)

1963-02-27
1964-05-29

New composition for hair use

FR1603826A
(en)

1968-12-09
1971-06-07

Dna-and rna-contg cosmetic prods

DE2509531A1
(en)

1975-03-05
1976-09-16
Thomae Gmbh Dr K

ANTIVIRAL AGENT

JPS59134706A
(en)

1983-01-19
1984-08-02
Kobayashi Kooc:Kk
Cosmetic

US4557934A
(en)

1983-06-21
1985-12-10
The Procter & Gamble Company
Penetrating topical pharmaceutical compositions containing 1-dodecyl-azacycloheptan-2-one

US4885157A
(en)

1987-02-13
1989-12-05
Fiaschetti Mary G
Dermal cosmetic composition and applications therefor

IT1222701B
(en)

1987-09-23
1990-09-12
Crinos Industria Farmaco

COMPOSITION FOR TOPICAL USE HAVING TRICHOGEN, ANTI-DANDRUFF AND ANTI-SEBORRHEIC ACTIVITY

FR2609393A1
(en)

1988-02-23
1988-07-15
Serobiologiques Lab Sa
Composition which is useful, in particular, as a base material for the preparation of pharmaceutical, in particular dermatological and/or cosmetic, compositions, comprising a nitrogenous substance, in particular amino acids, oligo- or polypeptides, proteins, and their derivatives, and pharmaceutical or cosmetic composition thus prepared

1989

1989-09-07
IT
IT8921650A
patent/IT1232318B/en
active

1990

1990-06-01
IL
IL9458290A
patent/IL94582A/en
not_active
IP Right Cessation

1990-06-08
NZ
NZ233987A
patent/NZ233987A/en
unknown

1990-07-20
AU
AU59169/90A
patent/AU631441B2/en
not_active
Ceased

1990-08-10
AT
AT90202171T
patent/ATE98868T1/en
not_active
IP Right Cessation

1990-08-10
DK
DK90202171.6T
patent/DK0416677T3/en
active

1990-08-10
EP
EP90202171A
patent/EP0416677B1/en
not_active
Expired – Lifetime

1990-08-10
DE
DE90202171T
patent/DE69005398T2/en
not_active
Expired – Fee Related

1990-08-16
GR
GR900100612A
patent/GR1000637B/en
unknown

1990-08-16
US
US07/568,125
patent/US5126331A/en
not_active
Expired – Fee Related

1990-09-03
JP
JP2230744A
patent/JPH0399017A/en
active
Pending

1990-09-05
PT
PT95211A
patent/PT95211B/en
not_active
IP Right Cessation

1990-09-05
CH
CH2881/90A
patent/CH682804A5/en
not_active
IP Right Cessation

1990-09-06
LU
LU87799A
patent/LU87799A1/en
unknown

1990-09-07
KR
KR90014173A
patent/KR970009581B1/en
not_active
IP Right Cessation

1990-09-07
BE
BE9000864A
patent/BE1003350A3/en
not_active
IP Right Cessation

1990-09-07
FR
FR909011104A
patent/FR2651434B1/en
not_active
Expired – Fee Related

1990-09-07
ES
ES9002332A
patent/ES2026754A6/en
not_active
Expired – Fee Related

Also Published As

Publication number
Publication date

US5126331A
(en)

1992-06-30

BE1003350A3
(en)

1992-03-03

DK0416677T3
(en)

1994-01-31

EP0416677B1
(en)

1993-12-22

IT8921650D0
(en)

1989-09-07

JPH0399017A
(en)

1991-04-24

NZ233987A
(en)

1992-10-28

FR2651434A1
(en)

1991-03-08

KR970009581B1
(en)

1997-06-14

LU87799A1
(en)

1991-02-18

FR2651434B1
(en)

1993-08-06

EP0416677A1
(en)

1991-03-13

PT95211A
(en)

1991-05-22

KR910005877A
(en)

1991-04-27

IL94582A0
(en)

1991-04-15

ES2026754A6
(en)

1992-05-01

ATE98868T1
(en)

1994-01-15

DE69005398D1
(en)

1994-02-03

GR900100612A
(en)

1992-01-20

GR1000637B
(en)

1992-09-11

AU5916990A
(en)

1991-03-14

CH682804A5
(en)

1993-11-30

PT95211B
(en)

1997-06-30

IL94582A
(en)

1994-10-07

IT1232318B
(en)

1992-01-28

DE69005398T2
(en)

1994-04-14

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