Advanced Treatment for Scars and Dark Spots
developed by a leading plastic surgeon

Probiosyn-4™

PROBIOSYN-4 NATURAL SCAR TREATMENT

natural scar treatment

InviCible contains a proprietary all-natural scar treatment complex called ProBiosyn-4™. This complex consists of aloe vera, licorice extract, and essential fatty acids (EFAs) linoleic and oleic acid.

ProBiosyn-4™ helps improve scar appearance in several ways. The independent scientific studies listed below show how these ingredients:

  • decrease inflammation
  • improve wound healing
  • improve skin moisture and scar elasticity
  • lighten dark pigmentation
  • have anti-acne effects

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ProBiosyn-4™:

Aloe Vera

 

Aloe Vera may help improve wound healing and decrease inflammation.
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Aloe Vera decreases inflammation when applied on the skin.
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Benefits of Aloe Vera in the treatment of scar tissue: the prevention of scar formation and its moisturizing emollient effect.
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Aloe Vera – A review of the scientific literature. In addition to wound healing benefits, Aloe Vera also has antibacterial and antifungal properties.
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Linoleic and Oleic Acids (EFAs)

 

Linoleic acid protects against skin breakdown, improves skin hydration and maintains skin elasticity.
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Linolenic acid lightens hyperpigmentation of the skin.
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Linoleic acid stimulates wound healing.
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Oleic Acid stimulates wound healing.
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Licorice (Stearyl Glycyrrhetinate)

 

Licorice extract lightens dark pigment and brown spots including melasma.
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Licorice extract is a strong anti-inflammatory.
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Licorice extract accelerates skin renewal.
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Licorice extract has strong anti-acne effects both in terms of prevention and treatment.
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ALOE VERA SCIENTIFIC STUDIES

The studies below show that Aloe Vera gel:

  • improves scar healing
  • decreases inflammation
  • is a valuable skin moisturizer
  • has antibacterial and antifungal properties

1. RH, DiDonato JJ, Hartman GM, et al. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc1994;84(2):77-81.

Aloe vera improves wound healing and inhibits inflammation. Since mannose-6-phosphate is the major sugar in the Aloe gel, the authors examined the possibility of its being an active growth substance. Mice receiving 300 mg/kg of mannose-6-phosphate had improved wound healing over saline controls. This dose also had anti-inflammatory activity. The function of mannose-6-phosphate in A. vera is discussed.

Editorial note: This study describes how Aloe vera improves wound healing and decreases inflammation.

Pubmed Abstract


2. Davis RH, Rosenthal KY, Cesario LR, Rouw GA. Processed Aloe vera administered topically inhibits inflammation. J Am Podiatr Med Assoc1989;79(8):395-7.

Aloe vera preparations were evaluated for topical anti-inflammatory activity using the croton oil-induced edema assay. The results show that small amounts of A. vera given topically will inhibit inflammation induced by a moderate amount of irritant. In general, the decolorized Aloe was more effective than the colorized Aloe (with anthraquinone). A 47.1% inhibition of inflammation was obtained by 5% decolorized irradiated Aloe. These results may be used as a baseline to assess the biologic activity of A. vera in the treatment of inflammation by podiatric physicians.

Editorial note: Aloe vera decreases inflammation when applied on the skin.

Pubmed Abstract


3. Eshun K, He Q. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries–a review. Crit Rev Food Sci Nutr 2004;44(2):91-6.

Scientific investigations on Aloe vera have gained more attention over the last several decades due to its reputable medicinal properties. Some publications have appeared in reputable Scientific Journals that have made appreciable contributions to the discovery of the functions and utilizations of Aloe – “nature’s gift.” Chemical analysis reveals that Aloe vera contains various carbohydrate polymers, notably glucomannans, along with a range of other organic and inorganic components. Although many physiological properties of Aloe vera have been described, it still remains uncertain as to which of the component(s) is responsible for these physiological properties. Further research needs to be done to unravel the myth surrounding the biological activities and the functional properties of A. vera. Appropriate processing techniques should be employed during the stabilization of the gel in order to affect and extend its field of utilization.

Editorial note: This review article describes the beneficial effects of Aloe Vera on scars. On page 94 the authors state “A. vera is a well known anti-inflammatory and wound healer, accelerating the rapid growth of epithelial tissue.” “Aloe vera is known to have a marked effect in the treatment of scar tissue and the prevention of scar formation following injury to the skin. This is because A. vera stimulates cell production through the activity of the amino acids, which are the basis for new cell formation, and also, due to the ability of its enzymes, promotes regeneration at the deepest layers of the skin“. Aloe vera also has a “valuable moisturizing emollient effect”. In conclusion (page 95) “there is scientific evidence for its beneficial properties”.

Pubmed Abstract


4. Klein AD, Penneys NS. Aloe vera. J Am Acad Dermatol1988 Apr;18(4 Pt 1):714-720.

We review the scientific literature regarding the aloe vera plant and its products. Aloe vera is known to contain several pharmacologically active ingredients, including a carboxypeptidase that inactivates bradykinin in vitro, salicylates, and a substance(s) that inhibits thromboxane formation in vivo. Scientific studies exist that support an antibacterial and antifungal effect for substance(s) in aloe vera. Studies and case reports provide support for the use of aloe vera in the treatment of radiation ulcers and stasis ulcers in man and burn and frostbite injuries in animals. The evidence for a potential beneficial effect associated with the use of aloe vera is sufficient to warrant the design and implementation of well-controlled clinical trials.

Editorial note: This review examines the body of scientific literature that exists on Aloe vera. Along with it’s many beneficial actions on wound healing, Aloe vera also has antibacterial and antifungal properties.

Pubmed Abstract


LINOLEIC ACID (Safflower Seed Oil) AND OLEIC ACID (Sunflower Seed Oil)

The studies below show that these essential fatty acids (EFAs):

  • improve wound healing
  • improve skin hydration
  • restore skin elasticity
  • lighten skin hyperpigmentation

1. Declair V. The usefulness of topical application of essential fatty acid (EFA) to prevent pressure ulcers. Ostomy Wound Manage1997;43(5):48-54.

This study investigated whether the topical application of linoleic acid improves hydration and elasticity and helps prevent breakdown in individuals with poor nutritional status. Between June 1995 and July 1996, 86 patients, equally divided into two groups, underwent double-blind research (mean age = 60; range 26 -78). All patients had a Norton Scale score of 9 and were fed orally a high-protein diet and/or received parenteral nutrition (92% were severely malnourished). Pressure ulcer prevention was the same for both groups. Every 8 hours, approximately 20ml of solution A (1.6gr EFA with linoleic acid, 112 UI Vitamin A, and 5 UI Vitamin E) or B (1.6gr mineral oil, 112 UI Vitamin A, and 5 UI Vitamin E) was applied all over the body inclusive of all potential wound sites for a mean of 21 days. In group A, two patients developed ulcers (both stage 1, one per patient); 42 (98%) had hydrated skin and 32 (76%) maintained skin elasticity. In group B, 12 (27%) developed ulcers (all stage II, ten with 1 ulcer, two with 2 ulcers); 9 (22%) had hydrated skin while 34 (78%) showed scaly skin/deep dehydration; 10 (24%) maintained skin elasticity while 33 (76%) showed a loss of elasticity. These results lead us to believe that essential fatty acids really do make a difference in the skin.

Editorial note: This double-blind study shows that Linoleic protects against skin breakdown, improves skin hydration and maintains skin elasticity.

Pubmed Abstract


2. Ando H, Ryu A, Hashimoto A, et al. Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin. Arch Dermatol Res1998 Jul;290(7):375-81.

This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the skin. An efficient lightening effect was observed following topical application of linoleic acid or alpha-linolenic acid to UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes. In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by alpha-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by alpha-linolenic acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and alpha-linolenic acid are, at least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment from the epidermis.

Editorial note: Linoleic acid accelerates removal of melanin (skin pigment) in the stratum corneum (the top layer of the epidermis) and also suppresses new melanin production. These actions lighten hyperpigmentation (which is often associated with prominent scars).

Pubmed Abstract


3. Ruthig DJ, Meckling-Gill KA. Both (n-3) and (n-6) fatty acids stimulate wound healing in the rat intestinal epithelial cell line, IEC-6. J Nutr1999 Oct;129(10):1791-8.

The control of proliferation and epithelial restitution are processes that are poorly understood. The effects of (n-3), (n-6) and trans fatty acids on proliferation of subconfluent IEC-6 cultures and restitution of wounded IEC-6 monolayers were investigated. Incorporation of supplemented fatty acids into cellular phospholipid was also assessed. Sulforhodamine B protein dye binding assay was utilized to assess the proliferative effects of fatty acids on growth of IEC-6 cultures. Incorporation of supplemental fatty acids into cellular phospholipid was examined by thin-layer chromatography combined with gas chromatography. The modulation of epithelial restitution was examined by razor blade wounding confluent IEC-6 monolayers grown in media supplemented with various fatty acids. Inhibition of eicosanoid synthesis by indomethacin during the wounding assay was also assessed. Both (n-3) and (n-6) fatty acids significantly inhibited growth of this intestinal epithelial cell model at concentrations above 125 micromol/L. The trans fatty acid, linoelaidate 18:2(n-6)trans, inhibited growth of IEC-6 cells at concentrations above 250 micromol/L. Another trans fatty acid, elaidate 18:1(n-9)trans, was well-tolerated at concentrations as high as 500 micromol/L. Eicosapentanoic 20:5(n-3), linoleic 18:2(n-6), alpha-linolenic 18:3(n-3), gamma-linolenic 18:3(n-6) and arachidonic 20:4(n-6) acids all significantly enhanced cellular migration in the IEC-6 model of wound healing. Eicosapentanoate, linoleate, alpha-linolenate, gamma-linolenate and arachidonate are all capable of improving reconstitution of epithelial integrity following mucosal injury. Inhibition of eicosanoid synthesis reduced the enhancement of restitution by n-6 fatty acids back to control levels.

Editorial note: Linoleic acid (n-6) improves wound healing in a rat model by enhancing cellular migration.

Pubmed Abstract


4. Cardoso CR, Souza MA, Ferro EA, Favoreto S Jr, Pena JD. Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds. Wound Repair Regen. 2004 Mar-Apr;12(2):235-43.

Injury triggers a series of physiological events at the wound site. These include an inflammatory response that is established shortly after the injury, which is then followed by an intense formation of tissue over a period of days. Poly- and monounsaturated fatty acids exert major functions on the inflammatory responses, either in the form of phospholipids anchored in the cell membrane or as soluble lipoic mediators. We present evidence that linolenic (n-3), linoleic (n-6), and oleic (n-9) fatty acids can modulate the closure of surgically induced skin wounds. We found that n-9 fatty acids induced faster wound closure when compared to n-3, n-6, and control. In addition, n-9 fatty acids strongly inhibited the production of nitric oxide at the wound site. A mild improvement on wound closure was observed in the n-6 fatty acid-treated animals concurrent with a peak in nitric oxide production at 48 hours postsurgery. N-3 fatty acid treatment significantly delayed wound closure. Furthermore, we showed that n-3 fatty acid induced a peak in nitric oxide at 3 hours postsurgery and an intense deposition of extracellular matrix after 5 days of treatment. Thus, our results suggest a relevant role and potential therapeutic implication for fatty acids on skin wound healing.

Editorial note: these results suggest Linoleic acid (n-6) and Oleic acid (n-9) both improve skin wound healing after surgery.

Pubmed Abstract


LICORICE (STEARYL GLYCYRRHETINATE) SCIENTIFIC STUDIES

The studies below show that topical Licorice extract:

  • is a strong anti-inflammatory
  • accelerates skin renewal
  • lightens dark pigment and brown spots
  • including melasma
  • has strong anti-acne effects both in terms of prevention and treatment

1. Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 1998 Dec;11(6):355-61.

Glabridin is the main ingredient in hydrophobic fraction of licorice extract affecting on skins. In this study, we investigated inhibitory effects of glabridin on melanogenesis and inflammation using cultured B16 murine melanoma cells and guinea pig skins. The results indicated that glabridin inhibits tyrosinase activity of these cells at concentrations of 0.1 to 1.0 microg/ml and had no detectable effect on their DNA synthesis. Combined analysis of SDS-polyacrylamide gel electrophoresis and DOPA staining on the large granule fraction of these cells disclosed that glabridin decreased specifically the activities of T1 and T3 tyrosinase isozymes. It was also shown that UVB-induced pigmentation and erythema in the skins of guinea pigs were inhibited by topical applications of 0.5% glabridin. Anti-inflammatory effects of glabridin in vitro were also shown by its inhibition of superoxide anion productions and cyclooxygenase activities. These data indicated that glabridin is a unique compound possessing more than one function; not only the inhibition of melanogenesis but also the inhibition of inflammation in the skins. By replacing each of hydroxyl groups of glabridin with others, it was revealed that the inhibitory effect of 2′-O-ethyl glabridin was significantly stronger than that of 4′-O-ethyl-glabridin on melanin synthesis in cultured B16 cells at the concentration of 1.0 mg/ml. With replacement of both of two hydroxyl groups, the inhibitory effect was totally lost. Based on these data, we concluded that two hydroxyl groups of glabridin are important for the inhibition of melanin synthesis and that the hydroxyl group at the 4′ position of this compound is more closely related to melanin synthesis.

Editorial note: Glabridin, a major constituent of licorice extract, decreases dark pigment and skin inflammation.

Pubmed Abstract


2. Tsukahara M, Nishino T, Furuhashi I, Inoue H, Sato T, Matsumoto H. Synthesis and inhibitory effect of novel glycyrrhetinic acid derivatives on IL-1 beta-induced prostaglandin E(2) production in normal human dermal fibroblasts. Chem Pharm Bull (Tokyo). 2005 Sep;53(9):1103-10.

Olean-11,13(18)-dien-3beta,30-diol dihemiphthalate (3), which was derived from glycyrrhetinic acid (GA), has been reported to produce a potent anti-inflammatory effect in in-vivo assays. Using 3 as a lead compound, we attempted to synthesize some modified compounds which varied in the following; i) the position of a carboxyl group in the phthalate moiety, ii) the number of carboxyls attached to the benzoyl group, iii) conversion of benzene ring to another ring system, iv) the linkage form between the benzene ring and oleanene skeleton at position 3 and/or 30. These were screened for their inhibitory activity against interleukin-1 beta (IL-1 beta)-induced prostaglandin E(2) (PGE(2)) production in normal human dermal fibroblasts (NHDF). Although conversion of the ortho-carboxyl group of 3 into the meta-position or the para-position led to an increase in inhibitory activity, the elimination or increase of the carboxyl group resulted in loss of the inhibitory activity. Conversion of the ester bond to the amide bond at position 3 and/or 30 of 3 did not contribute to a significant increase in inhibitory activity. On the other hand, among the derivatives possessing an anthranilic acid moiety at position 30 of 3beta-O-acetyl-olean-11,13(18)-dien-30-oic acid (20), 3beta-hydroxy-30-nor-olean-11,13(18)-dien-20 beta-[N-(2-carboxyphenyl)]carboxamide (30) showed the most potent inhibitory activity (IC(50) 1.0 microM) in this series.

Editorial note: Licorice extract derivatives decrease inflammation by inhibiting IL-2.

Pubmed Abstract


3. Amer M, Metwalli M. Topical liquiritin improves melasma. Int J Dermatola. 2000 Apr;39(4):299-301.

Twenty women with a clinical diagnosis of melasma were treated with liquiritin cream on one side of the face and with a vehicle cream on the other side twice daily for 4 weeks. Patients were advised to avoid sun exposure and/or used topical sunscreen during the entire period of treatment. Inclusion criteria included an age range from 18 to 40 years and bilateral and symmetrical idiopathic epidermal melasma. Exclusion criteria included patients with dermal melasma (differentiated by Wood’s light), melasma with pregnancy, and patients currently receiving hormone replacement therapy. Melasma pigmentary intensity was rated on a five-point scale in relation to the patient’s normal facial skin (1, no difference; 2, slightly more pigmented; 3, moderately more pigmented; 4, markedly more pigmented; and 5, intensely more pigmented). The size of the lesions was measured directly using a millimeter grid scale. Ratings and measurements were made prior to treatment and at each of the follow-up visits (after 2, 4, 6, 8, and 10 weeks). Clinical evaluation was performed at week 4; the overall response was rated as excellent, good, fair, or poor. Color photographs were taken at the start and at week 4 of the study. Side-effects were observed and treated.

Editorial note: This clinical trial showed Licorice extract derivatives significantly decrease melasma hyperpigmentation and speed up renewal of the top layer of the skin.

Pubmed Abstract


4. Nam C, Kim S, Sim Y, Chang I. Anti-acne effects of Oriental herb extracts: a novel screening method to select anti-acne agents. Skin Pharmacol Appl Skin Physiol. 2003 Mar-Apr;16(2):84-90.

The acne-therapeutic effects of Oriental herb extracts were investigated in terms of antichemotactic effect on polymorphonuclear leucocytes, antilipogenic actions, antibacterial activity against Propionibacterium acnes and resistance induction potency in the bacteria. The ethanol extract (0.01%) of Angelica dahurica markedly suppressed neutrophil chemotaxis, comparable to the effect of erythromycin (0.01%), whereas a strong antilipogenic effect was obtained with rhizoma coptidis (Coptis chinensis) extract (0.01%), leading to a higher efficacy than that of retinoic acid (0.01%). Interestingly, only Glycyrrhiza glabra showed a remarkable antibacterial activity against P. acnes, resulting in negligible induction of resistance, in comparison with a marked development of resistance in the bacteria treated with erythromycin. We suggest that an appropriate formulation containing A. dahurica, rhizoma coptidis and G. glabra could be helpful for the prevention and treatment of acne lesions.

Editorial note: Licorice extract derivatives have significant anti-bacterial activity against Propionibacterium acnes, the bacterium responsible for acne breakouts.

Pubmed Abstract

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