(19)
(11)EP 3 347 009 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
13.10.2021 Bulletin 2021/41

(21)Application number: 16820583.9

(22)Date of filing:  05.05.2016
(51)International Patent Classification (IPC): 
A61K 31/4045(2006.01)
A61P 17/14(2006.01)
C07C 35/21(2006.01)
A61K 45/06(2006.01)
A61K 31/05(2006.01)
A61Q 7/00(2006.01)
C07D 209/16(2006.01)
(52)Cooperative Patent Classification (CPC):
A61K 31/4045; C07C 39/21; A61K 8/347; A61Q 7/00; A61P 17/14; A61K 31/05; A61K 8/492; C07D 209/16
 
C-Sets:
  1. A61K 31/05, A61K 2300/00;
  2. A61K 31/4045, A61K 2300/00;

(86)International application number:
PCT/CA2016/000132
(87)International publication number:
WO 2017/004692 (12.01.2017 Gazette  2017/02)

(54)

COMPOSITION COMPRISING RESVERATROL AND MELATONIN FOR REDUCING HAIR LOSS AND/OR INCREASING HAIR REGROWTH

ZUSAMMENSETZUNGEN MIT RESVERATROL UND MELATONIN ZUR REDUZIERUNG VON HAARAUSFALL UND/ODER ZUR ERHÖHUNG DES ERNEUTEN HAARWACHSTUMS

COMPOSITION COMPRENANT DU RESVÉRATROL ET DE LA MÉLATONINE POUR RÉDUIRE LA CHUTE DES CHEVEUX ET/OU AMÉLIORER LA REPOUSSE DES CHEVEUX


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 08.07.2015 US 201562190044 P

(43)Date of publication of application:
18.07.2018 Bulletin 2018/29

(73)Proprietor: Triple Hair Inc.
Dieppe, New Brunswick E1A 6R8 (CA)

(72)Inventor:
  • SEKHAVAT, Houfar
    Dieppe, New Brunswick E1A 6R8 (CA)

(74)Representative: Boult Wade Tennant LLP 
Salisbury Square House 8 Salisbury Square
London EC4Y 8AP
London EC4Y 8AP (GB)


(56)References cited: : 
WO-A1-2011/039175
US-A1- 2011 183 016
CA-A1- 2 838 646
US-B1- 6 281 241
  
  • KYOUNG JA KWON ET AL: "Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways", JOURNAL OF CLINICAL NEUROLOGY, vol. 6, no. 3, 15 April 2010 (2010-04-15), page 127, XP055037213, ISSN: 1738-6586, DOI: 10.3988/jcn.2010.6.3.127
  • KISKOVA ET AL.: 'A COMBINATION OF RESVERATROL AND MELATONIN EXERTS CHEMOPROTECTIVE EFFECTS IN N-METHY-N-NITROSOURCEA-INDUCED RAT MAMMARY CARCINOGENESIS.' EUROPEAN JOPURNAL OF CANCER PREVENTION vol. 21, 2012, pages 163 - 170, XP009507305
  • FISCHER: 'Melatonin increases angen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.' BRITISH JOURNAL OF DERMATOLOGY vol. 150, no. 2, 19 February 2004, pages 341 - 345, XP055342479
  • SARDI,B: 'ATTENTION ALL BALDING MALES: RESVERATROL TO YOUR RESCUE' RESVERATOL NEWS, [Online] 02 April 2012, XP055497558 Retrieved from the Internet: <URL:http://www.resveratrolnews.com/attenti on-all-balding-males-resveratrol-vour-rescu e/520> [retrieved on 2016-06-14]
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description

FIELD OF INVENTION



[0001] The inventor has discovered that a composition comprising resveratrol and melatonin shows improved properties in terms of reducing hair loss and increasing hair regrowth when compared to conventional therapies, such as the topical application of a solution of 5% minoxidil.

BACKGROUND OF THE INVENTION



[0002] Androgenetic alopecia (AGA) is hair loss (at scalp level) caused by the thinning of hair follicles. It is very common in men between the age of 19 and 70 years. Notably, more than 50% of Caucasian men in their fifties are affected by it. Women's hair loss mostly becomes an issue after menopause.

[0003] Individuals affected by androgenetic alopecia (AGA) show a diminution of their self-esteem that can effect negatively many facets of their lives. The inventor has discovered that a composition for topical administration comprising resveratrol and melatonin is effective in reducing hair loss and increasing hair regrowth.

[0004] There are several hair loss prevention products on the market. By way of example, minoxidil has been in use since the 1990s in topical form at 2% concentration (without prescription) and at 3% and 5% concentration (with prescription). While studies demonstrate the efficiency of 5% minoxidil over the 2% concentration, minoxidil is less than 40% effective in promoting regrowth of the hair. Minoxidil is considered the topical gold standard available for treatment of hair loss.

[0005] Another hair loss prevention product is finasteride. It is administered orally usually at a dosage of 1 mg/day. There are a number of side effects associated with the administration of finasteride including lowered libido, impotence, ejaculation disorders, allergic reactions, testicular pain, male infertility, male breast cancer and depression. At higher concentrations (5 mg), finasteride can cause benign prostate hyperplasia.

[0006] US2011/183016 discloses compositions containing chitosan which form a film after application onto the scalp or hair. US6281241 discloses the use of melatonin for the treatment of androgenetic alopecia of the female type. WO2011039175 discloses the use of resveratrol for the preparation of a medicament for the treatment of acne, rosacea or androgenetic alopecia. Kiskova et al. (Eur J Cancer Pre. 2012 Mar;21(2): 163-70.) disclose that a combination of resveratrol and melatonin exerts chemoprotective effects in N-methyl-N-nitrosourea-induced rat mammary carcinogenesis. Fischer et al. (Br J Dermatol. 2004 Feb;150(2):341-5) disclose melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia.

[0007] The inventor has discovered that a composition comprising resveratrol and melatonin for topical application to the scalp reduces hair loss and increases hair regrowth. Such a composition shows superior improvements to those seen for each of the components of the composition taken individually and to a composition comprising 5% minoxidil and the results obtained to date suggest that the improvements may be superior to those of the sum of the said components.

SUMMARY OF INVENTION



[0008] The invention provides a composition for therapeutic use in reducing hair loss, increasing regrowth of hair, or reducing hair loss and increasing regrowth of hair in a human subject, the composition comprising 0.01% to 15% of resveratrol and 0.01% to 15% of melatonin, wherein the composition is administered topically.

[0009] The invention also provides a non-therapeutic method for reducing hair loss, increasing regrowth of hair, or in reducing hair loss and increasing regrowth of hair in a human subject, the non-therapeutic method comprising applying topically to a human subject a composition comprising 0.01% to 15% of resveratrol and 0.01% to 15% of melatonin.

BRIEF DESCRIPTION OF THE FIGURES



[0010] 

Figures 1A to 1C are a series of photographs showing the scalp of participant 1 prior to treatment on the first day of month one (Fig. 1A) and at months three (Fig. 1B) and six (Fig. 1C) of a six month treatment with a solution of 5% resveratrol and 0.1% melatonin;

Figures 2A to 2C are a series of photographs showing the scalp of participant 2 prior to treatment on the first day of month one (Fig. 2A) and at months three (Fig. 2B) and six (Fig. 2C) of a six month treatment with a solution of 5% resveratrol and 0.1% melatonin;

Figures 3A to 3C are a series of photographs showing the scalp of participant 3 prior to treatment on the first day of month one (Fig. 3A) and at months three (Fig. 3B) and six (Fig. 3C) of a six month treatment with a solution of 5% resveratrol and 0.1% melatonin;

Figures 4A to 4C are a series of photographs showing the scalp of participant 4 prior to treatment on the first day of month one (Fig. 4A) and at months three (Fig. 4B) and six (Fig. 4C) of a six month treatment with a solution of 5% resveratrol and 0.1% melatonin;

Figures 5A to 5C are a series of photographs showing the scalp of participant 5 prior to treatment on the first day of month one (Fig. 5A) and at months three (Fig. 5B) and six (Fig. 5C) of a six month treatment with a solution of 5% resveratrol and 0.1% melatonin;

Figures 6A to 6C are a series of photographs showing the scalp of participant 6 prior to treatment on the first day of month one (Fig. 6A) and at months three (Fig. 6B) and six (Fig. 6C) of a six month treatment with a solution of 5% resveratrol and 0.1% melatonin;

Figure 7A to 7C are a series of photographs showing the scalp of participant 7 prior to treatment (Fig. 7A) and at months three (Fig. 7B) and six (Fig. 7C) of a six month treatment with a solution of 5% minoxidil only;

Figure 8A to 8C are a series of photographs showing the scalp of participant 8 prior to treatment (Fig. 8A) and at months three (Fig. 8B) and six (Fig. 8C) of a six month treatment with a solution of 5% minoxidil only;

Figure 9A to 9C are a series of photographs showing the scalp of participant 9 prior to treatment (Fig. 9A) and at months three (Fig. 9B) and six (Fig. 9C) of a six month treatment with a solution of 5% minoxidil only;

Figure 10A to 10C are a series of photographs showing the scalp of participant 10 prior to treatment (Fig. 10A) and at months three (Fig. 10B) and six (Fig. 10C) of a six month treatment with a solution of 5% minoxidil only;

Figure 11A to 11C are a series of photographs showing the scalp of participant 11 prior to treatment (Fig. 11A) and at months three (Fig. 11B) and six (Fig. 11C) of a six month treatment with a solution of 5% resveratrol only;

Figure 12A to 12C are a series of photographs showing the scalp of participant 12 prior to treatment (Fig. 12A) and at months three (Fig. 12B) and six (Fig. 12C) of a six month treatment with a solution of 5% resveratrol only;

Figure 13A to 13C are a series of photographs showing the scalp of participant 13 prior to treatment (Fig. 13A) and at months three (Fig. 13B) and six (Fig. 13C) of a six month treatment with a solution of 5% resveratrol only;

Figure 14A to 14C are a series of photographs showing the scalp of participant 14 prior to treatment (Fig. 14A) and at months three (Fig. 14B) and six (Fig. 14C) of a six month treatment with a solution of 0.1% melatonin only;

Figure 15A to 15C are a series of photographs showing the scalp of participant 15 prior to treatment (Fig. 15A) and at months three (Fig. 15B) and six (Fig. 15C) of a six month treatment with a solution of 0.1% melatonin only;

Figure 16A to 16C are a series of photographs showing the scalp of participant 16 prior to treatment (Fig. 16A) and at months three (Fig. 16B) and six (Fig. 16C) of a six month treatment with a solution of 0.1% melatonin only;

Figure 17A to 17C are a series of photographs showing the scalp of participant 17 prior to treatment (Fig. 17A) and at months three (Fig. 17B) and six (Fig. 17C) of a six month treatment with a solution of 0.1% melatonin only; and

Figure 18A to 18C are a series of photographs showing the scalp of participant 18 prior to treatment (Fig. 18A) and at months three (Fig. 18B) and six (Fig. 18C) of a six month treatment with a solution of 0.1% melatonin only;


DETAILED DESCRIPTION OF THE INVENTION



[0011] The invention relates to a topical composition comprising resveratrol and melatonin which shows improved properties for the reduction of hair loss and for the increase of hair regrowth in human subjects when compared to minoxidil.

[0012] Resveratrol is a natural product in topical form derived from polygonum multiflorum, an Asian cane.

[0013] Melatonin is mostly used to treat insomnia. The FDA classifies melatonin as a dietary supplement.

[0014] An exemplary composition described herein comprises 0.01% to 15% resveratrol and 0.01% to 15% of melatonin. In another instance, the composition comprises 5% resveratrol and 0.01% melatonin.

[0015] In order to demonstrate the improved properties of a composition suitable for topical application comprising resveratrol and melatonin, the composition was compared to compositions comprising 5% minoxidil only, 0.1% melatonin only and 5% resveratrol only. The various compositions were prepared as follows.

Example 1:


Preparation of Composition Comprising Resveratrol and Melatonin



[0016] The composition comprises 5% resveratrol and 0.1% melatonin as the active ingredients and propylene glycol and absolute ethyl alcohol as non-active ingredients. The alcohol also serves as the final preservative in the composition.

[0017] Various modifications for the preparation of the composition of the invention will be apparent to the skilled worker. Furthermore, other pharmaceutically acceptable additives such as suspending agents, emulsifying agents, non-aqueous vehicles and preservatives can be added. The techniques for the preparation of these compositions are well known in the art and reference may be had to Remington's Pharmaceutical Sciences, 18th edition, Mack Publishing Co., Easton, Pennsylvania, USA 18042.

Example 2 (provided for reference only):


Preparation of Composition Comprising Minoxidil



[0018] A composition comprising 5% minoxidil was prepared. Absolute ethyl alcohol was mixed with propylene glycol and heated to 55° to 65°C. The minoxidil powder was added to the alcohol/propylene glycol mixture. Ethoxy diglycol was added and the solution was stirred. The final solution was brought to volume with absolute ethyl alcohol to obtain a solution comprising 5% minoxidil.

Example 3 (provided for reference only):


Preparation of Composition Comprising Resveratrol



[0019] A composition comprising 5% resveratrol was also prepared. Absolute ethyl alcohol was mixed with propylene glycol. Resveratrol was added to the alcohol/propylene glycol mixture to obtain a solution having a concentration of 5% resveratrol. Absolute ethyl alcohol also serves the function of preservative.

Example 4 (provided for reference only):


Preparation of Composition Comprising Melatonin



[0020] A solution comprising 0.1% melatonin was prepared. Absolute ethyl alcohol was mixed with propylene glycol. The melatonin was added to the alcohol/propylene glycol mixture. The final solution was brought to volume with absolute ethyl alcohol in order to obtain a solution having a concentration of 0.01% melatonin. The absolute ethyl alcohol also serves the function of preservative in this composition.

Example 5:


Treatment of Participants With Composition of Invention and Comparators - Analysis and Measurements



[0021] Each participant had androgenetic alopecia.

[0022] For each participant, the distance between the base of the nose and the middle of the hair crown was noted, as well as the distance separating the most distal part of the helix and the hair crown. A square area of two centimeters by two centimeters was measured around the middle point of the hair crown (marked by a washable felt crayon).

[0023] The participants were seen at monthly intervals over a six-month period and their hair was analysed in the manner described above.

Results


A. Treatment With Composition Comprising Resveratrol and Melatonin



[0024] Each participant first had his hair analysed as described above. Following the first analysis, each participant was provided with a solution comprising 5% resveratrol, and 0.1% melatonin prepared as described in Example 1 above. The participants applied 1 ml to the scalp, once a day after cleansing. The 1 ml was applied as 10 metered dose sprays of 0.1 ml.

[0025] The results for six participants are provided. Particulars of each participants are provided in Table 1 below. All six participants had androgenic alopecia, as did the participants of their comparator groups.
Table 1
ParticipantGenderAge
1 Male 38
2 Male 38
3 Male 36
4 Male 45
5 Male 32
6 Male 57


[0026] Figures 1 to 6 clearly show a decrease of hair loss and an increase in hair regrowth in all six participants.

[0027] Each participant completed a self-assessment questionnaire (Barber, Kaufman, Kozloff, Girman and Guess, A Hair Growth Questionnaire For Use In The Evaluation Of Therapeutic Effects In Men, Journal of Dermatological Treatment, Volume 9, Issue 3, 1998). All participants agreed that they could see their bald spot getting smaller after receiving treatment. 84% of the participants saw an improvement in the appearance of their hair. 83% of the participants saw a slight to moderate increase in the growth of their hair while all participants found that the treatment had been somewhat to very effective at slowing down hair loss.

[0028] A marked decrease of hair loss and an increase in hair regrowth was observed for each participant.

B. Comparison with Treatment With Minoxidil, Resveratrol and Melatonin



[0029] Each participant first had his hair analysed as described in part A above. Following the first analysis, each participant was provided with a solution comprising either 5% minoxidil, 5% resveratrol, or 0.1% melatonin. The compositions were prepared as described in Examples 2 to 4 above. The participants applied 1 ml to the scalp, once a day after cleansing. The 1 ml was applied as 10 metered dose sprays of 0.1 ml.

a) 5% Minoxidil Comparator



[0030] Four participants were provided with a solution of 5% minoxidil. The particulars of the participant are provided in Table 2 below.
Table 2
ParticipantGenderAge
7 Male 64
8 Male 45
9 Male 52
10 Male 48


[0031] Only a slight improvement in hair regrowth is observed for the minoxidil group and the results are inferior to those seen with the composition of the invention.

[0032] The four participants completed the self-assessment questionnaire described above. Half of the participants agreed that their bald spot decreased in size and that the appearance of their hair was a little better. 75% of the participants saw a little increase in the growth of their hair and found the treatment somewhat effective in slowing down hair loss.

b) 5% Resveratrol Comparator



[0033] Three participants were provided with a solution of 5% resveratrol. Particulars of the participants are provided in the Table 3 below.
Table 3
ParticipantGenderAge
11 Male 38
12 Male 31
13 Male 42


[0034] Only a slight improvement in hair regrowth is observed for the resveratrol only group. The results are inferior to those seen with the composition of the invention.

[0035] Two of the participants disagreed that their bald spot had gotten smaller and the other participants had no opinion. Two of the participants thought that the appearance of their hair was the same as before treatment and one thought that it was worse. All participants saw a slight increase in the growth of their hair. Two out of the three participants thought that the treatment was somewhat effective at slowing down hair loss while the other participant thought it was not very effective. c) 0.1% Melatonin Comparator

[0036] Five participants were provided with a solution of 0.1% melatonin only. The particulars of these participants are provided in Table 4 below.
Table 4
ParticipantGenderAge
14 Male 35
15 Female 36
16 Male 45
17 Male 42
18 Male 40


[0037] Only a slight improvement in hair regrowth was observed for the melatonin only group. The results obtained are inferior to those observed with the composition of the invention.

[0038] The self-assessment questionnaire reflected the fact that 80% of the participants either disagreed or strongly disagreed that their bald spot had gotten smaller and the remaining 20% had no opinion. 60% of the participants were of the view that the appearance of the hair remained unchanged, 20% believed it had gotten worse while 20% thought it was a little better. 80% of the participants saw no change in the growth of their hair while 20% saw a slight increase. 80% of the participants were of the view that the treatment was not very affective at slowing down hair loss and 20% thought it was not effective at all.

[0039] The composition comprising resveratrol and melatonin shows improved properties in terms of reduction of hair loss and increase of regrowth of hair when compared to a solution of 5% minoxidil alone, a solution of 5% resveratrol alone or a solution of 0.1% melatonin alone. The improvements shown in the reduction of hair loss and the increase of regrowth hair for the composition of the invention are superior to the improvements seen for each of the components of the composition taken individually and the results obtained to date suggest that the improvements may be superior to those of the sum of the said components.

[0040] While the composition of the invention has been tested on males, similar results are expected on females as the mechanism of hair growth is the same for both genders.


Claims

1. A composition for therapeutic use in reducing hair loss, increasing regrowth of hair, or reducing hair loss and increasing regrowth of hair in a human subject, the composition comprising 0.01% to 15% of resveratrol and 0.01% to 15% of melatonin, wherein the composition is administered topically.
 
2. The composition for therapeutic use according to claim 1 comprising 5% of resveratrol and 0.01% of melatonin.
 
3. The composition for therapeutic use of claim 1 or claim 2, wherein the human subject is a male.
 
4. The composition for therapeutic use of claim 1 or claim 2, wherein the human subject is a female.
 
5. The composition for therapeutic use according to claim 1 which is in the form of a spray.
 
6. A non-therapeutic method for reducing hair loss, increasing regrowth of hair, or in reducing hair loss and increasing regrowth of hair in a human subject, the non-therapeutic method comprising applying topically to a human subject a composition comprising 0.01% to 15% of resveratrol and 0.01% to 15% of melatonin.
 
7. The non-therapeutic method according to claim 6, wherein the composition comprises 5% of resveratrol and 0.01% of melatonin
 
8. The non-therapeutic method according to claim 6, wherein the human subject is a male.
 
9. The non-therapeutic method according to claim 6, wherein the human subject is a female.
 
10. The non-therapeutic method according to claim 6, wherein the composition is applied in the form of a spray.
 


Ansprüche

1. Zusammensetzung zur therapeutischen Verwendung bei der Verringerung des Haarausfalls, der Steigerung des Haarwachstums oder der Verringerung des Haarausfalls und der Steigerung des Haarwachstums bei einem Menschen, wobei die Zusammensetzung 0,01% bis 15% Resveratrol und 0,01% bis 15% Melatonin umfasst, wobei die Zusammensetzung topisch verabreicht wird.
 
2. Zusammensetzung zur therapeutischen Verwendung nach Anspruch 1, die 5 % Resveratrol und 0,01 % Melatonin umfasst.
 
3. Zusammensetzung zur therapeutischen Verwendung nach Anspruch 1 oder Anspruch 2, wobei der Mensch ein Mann ist.
 
4. Zusammensetzung zur therapeutischen Verwendung nach Anspruch 1 oder Anspruch 2, wobei der Mensch eine Frau ist.
 
5. Zusammensetzung zur therapeutischen Verwendung nach Anspruch 1, die in Form eines Sprays vorliegt.
 
6. Nicht-therapeutisches Verfahren zur Verringerung des Haarausfalls, zur Steigerung des Haarwachstums oder zur Verringerung des Haarausfalls und zur Steigerung des Haarwachstums bei einem Menschen, wobei das nichttherapeutische Verfahren die topische Anwendung einer Zusammensetzung, die 0,01% bis 15% Resveratrol und 0,01% bis 15% Melatonin umfasst, auf einen Menschen umfasst.
 
7. Nichttherapeutisches Verfahren nach Anspruch 6, bei dem die Zusammensetzung 5 % Resveratrol und 0,01 % Melatonin umfasst.
 
8. Nicht-therapeutisches Verfahren nach Anspruch 6, bei dem der Mensch ein Mann ist.
 
9. Nicht-therapeutisches Verfahren nach Anspruch 6, bei dem der Mensch eine Frau ist.
 
10. Nicht-therapeutisches Verfahren nach Anspruch 6, bei dem die Zusammensetzung in Form eines Sprays aufgetragen wird.
 


Revendications

1. Composition à usage thérapeutique dans la réduction de la chute des cheveux, l'augmentation de la repousse des cheveux, ou la réduction de la chute des cheveux et l'augmentation de la repousse des cheveux chez un sujet humain, la composition comprenant de 0,01 % à 15 % de resvératrol et de 0,01 % à 15 % de mélatonine, dans laquelle la composition est administrée par voie topique.
 
2. Composition à usage thérapeutique selon la revendication 1, comprenant 5 % de resvératrol et 0,01 % de mélatonine.
 
3. Composition à usage thérapeutique selon la revendication 1 ou la revendication 2, dans laquelle le sujet humain est un homme.
 
4. Composition à usage thérapeutique selon la revendication 1 ou la revendication 2, dans laquelle le sujet humain est une femme.
 
5. Composition à usage thérapeutique selon la revendication 1, qui est sous la forme d'un spray.
 
6. Procédé non thérapeutique pour réduire la perte de cheveux, augmenter la repousse des cheveux, ou pour réduire la perte de cheveux et augmenter la repousse des cheveux chez un sujet humain, le procédé non thérapeutique comprenant une application topique à un sujet humain d'une composition comprenant de 0,01 % à 15 % de resvératrol et de 0,01 % à 15 % de mélatonine.
 
7. Procédé non thérapeutique selon la revendication 6, dans lequel la composition comprend 5 % de resvératrol et 0,01 % de mélatonine.
 
8. Procédé non thérapeutique selon la revendication 6, dans lequel le sujet humain est un homme.
 
9. Procédé non thérapeutique selon la revendication 6, dans lequel le sujet humain est une femme.
 
10. Procédé non thérapeutique selon la revendication 6, dans lequel la composition est appliquée sous la forme d'un spray.
 




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Cited references

REFERENCES CITED IN THE DESCRIPTION



This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description




Non-patent literature cited in the description