Kojiplus Tube
Kojiplus Tube Uses, Dosage, Side Effects, Food Interaction and all others data.
Extracted from the dried leaves of bearberry plant in the genus Arctostaphylos and other plants commonly in the Ericaceae family, arbutin is a beta-D-glucopyranoside of Hydroquinone. It is found in foods, over-the-counter drugs, and herbal dietary supplements . Most commonly, it is an active ingredient in skincare and cosmetic products as a skin-lightening agent for the prevention of melanin formation in various skin conditions that involve cutaneous hyperpigmentation or hyperactive melanocyte function . It has also been used as an anti-infective for the urinary system as well as a diuretic . Arbutin is available in both natural and synthetic forms; it can be synthesized from acetobromglucose and Hydroquinone . Arbutin is a competitive inhibitor of tyrosinase (E.C.1.14.18.1) in melanocytes , and the inhibition of melanin synthesis at non-toxic concentrations was observed in vitro. Arbutin was shown to be less cytotoxic to melanocytes in culture compared to Hydroquinone .
At non-toxic concentrations, arbutin inhibited the activity of tyrosinase in cultured human keratinocytes, while having minimal effect on the expression of tyrosinase mRNA or the synthesis of the enzyme . α-Arbutin produced a concentration-dependent inhibition of melanin synthesis of human melanoma cells, HMV-II . No inhibitory effect on HMV-II cell growth was seen at concentrations lower than 1.0 mM. At concentrations of 0.5 mM of arbutin, tyrosinase activity was reduced to 60% of that in non-treated cells . The addition of arbutin blocked and inhibited α-MSH-stimulated melanogenesis in B16 melanoma cells, brownish guinea pig, and human skin tissue . In a pilot study of healthy male adults exposed to UV B irradiation, topical administration of arbutin inhibited UV-induced nuclear factor-kappaB activation in human keratinocytes . In mouse skin, arbutin counteracted oxidative stress induced by 12-O-tetradecanoylphorbol-13-acetate .
Hyaluronic acid (HA) is an anionic, nonsulfated glycosaminoglycan found in connective, epithelial, and neural tissues; it was first isolated in 1934. Karl Meyer and John Palmer obtained glycosaminoglycan (GAG) from the bovine eye, giving it the name “hyaluronic acid”. HA is involved in many important physiological processes, including but not limited to wound healing, tissue regeneration, and joint lubrication. It demonstrates unique viscoelasticity, moisturizing, anti-inflammatory qualities, and other important properties that prove beneficial in various clinical applications.
HA is used in drug delivery systems for the treatment of cancer, ophthalmological conditions, joint conditions, and aesthetic imperfections. Several preparations of hyaluronic acid have been approved by the FDA and are available in oral, topical, and injectable forms. A popular use of hyaluronic acid in recent years is cosmetic injection due to its ability to minimize the appearance of wrinkles and aging-related skin imperfections.
HA has long-acting lubricant, shock absorbing, joint stabilizing, and water balancing properties. It is similar to the naturally occurring glycosaminoglycan (GAG) in joints. Hyaluronic acid works by acting as a lubricant and shock absorber, facilitating joint mobility and thereby reducing osteoarthritic pain. Hyaluronic acid has antioxidative, anti-inflammatory, and analgesic effects. The water-balancing properties and viscoelasticity of hyaluronic acid are beneficial in cosmetic injections, imparting volume and reducing the appearance of imperfections and wrinkles. Due to the abovementioned properties, HA has a protective effect on the eyes and cornea.
| Trade Name | Kojiplus Tube |
| Generic | Kojic Acid + Arbutin + Licorice Extract + Tetrahydrocurcumin + Pine Bark Extract + Hyaluronic Acid + Wheat Germ Oil |
| Weight | 2% |
| Type | Skin LighteninCream |
| Therapeutic Class | |
| Manufacturer | General Medicine Therapeutics Pvt Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Indicated for over-the-counter use for epidermal hyperpigmentation in various skin conditions, such as melasma, freckles, and senile lentigines.
Hyaluronic acid is a glycosaminoglycan used for the relief of joint pain, wound healing, ophthalmologic treatment, cosmetic treatment, and various other applications.
The intra-articular preparations of hyaluronic acid are indicated for knee pain associated with osteoarthritis. Hyaluronic acid is used in cosmetic applications to prevent and reduce the appearance of wrinkles on the face, and as a dermal filler to correct facial imperfections or other imperfections on other parts of the body. It is frequently an ingredient in topical applications for wound healing and symptomatic treatment of skin irritation from various causes. Hyaluronic acid may also be indicated in ophthalmological preparations or oral capsules to treat discomfort caused by dry eyes or conjunctivitis and for its protective qualities during and before eye surgery. Finally, hyaluronic acid can be used off-label to coat the bladder for relief of interstitial cystitis symptoms.
Kojiplus Tube is also used to associated treatment for these conditions: Mild Lower Urinary Tract InfectionActinic Keratosis (AK), Burns, Chronic Skin Ulcers, Conjunctivitis, Dehydration, Dermabrasion, Dermatosis, Dry Eyes, Facial Defect, Interstitial Cystitis, Keratoconjunctivitis, Ocular Irritation, Osteoarthritis (OA), Pain of the knee, Seasonal Allergic Conjunctivitis, Skin Burn, Skin Irritation, Skin fissures, Tissue Adhesions, Varicose Ulcers, Wounds, Eye discomfort, Facial fine wrinkling, Sensation of burning in the eyes, Superficial Wounds, Dermal Filler, Synovial Fluid Lubrication, Wound Healing
How Kojiplus Tube works
Arbutin is a hydroquinone glycoside, however the hydroquinone moiety is not solely responsible for the de-pigmentating actions of arbutin . It acts as a competitive inhibitor of tyrosinase enzyme by acting on the L-tyrosine binding site to suppress melanogenesis and mediate its de-pigmenting actions on human skin . Tyrosinase is an enzyme involved in the regulation of rate-limiting steps during the synthesis of melanin; it regulates the conversion of L-tyrosine into L-dopa, and subsequent conversion of L-dopa to L-dopaquinone . Via inhibition of tyrosinase activity in a concentration-dependent manner, arbutin attenuates the production of melanin in melanocytes. While most studies suggest that arbutin has negligible effect on the tyrosinase mRNA expression, a study assessing the effect of arbutin on melanocyte differentiation inducement system using ES cells propose that arbutin may also downregulate the expression of tyrosinase in addition to its inhibitory action on the enzyme . The contradictory findings across studies may be due to previous studies using terminally-differentiated melanocytes and melanoma cells .
General principles and hyaluronic acid receptor binding
Hyaluronic acid works by two basic mechanisms: serving as a passive structural molecule or serving as signaling molecule, depending on the molecule size. The physicochemical properties of high molecular weight HA contribute to passive structural effects, demonstrating hygroscopicity and viscoelasticity and improving hydration, water balance, and structural integrity. As a signalling molecule interacting with proteins, HA causes several opposing effects based on molecular weight: pro- or anti-inflammatory effects, promotion or inhibition of cell migration, and activating or inhibiting cell division.
Hyaluronic acid exerts its therapeutic effects through binding to three primary types of cell surface receptors: CD44 (a membrane glycoprotein), the receptor for hyaluronate-mediated motility (RHAMM), and the Intercellular Adhesion Molecule 1 (ICAM-1). CD44 is considered the most widely distributed receptor for hyaluronic acid, demonstrating cellular interactions with osteopontin, collagen, and matrix metalloproteinases (MMPs). High and low molecular weight hyaluronic acids demonstrate differing molecular and cellular mechanisms in their interaction with CD44 receptors. Some examples of these effects include modification of chondrocyte survival pathways in addition to alteration of apoptosis pathways. Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), and hyaluronic acid receptor for endocytosis (HARE), (also known as Stabilin-2) also bind to hyaluronic acid.
Hyaluronic acid for skin conditions and cosmetics
Hyaluronic acid's anionic proprieties cause it to attract water and induce swelling, increasing tissue volume and skin structural integrity. The aging process is associated with reduced production of skin hyaluronic acid and collagen, causing the appearance of wrinkles and the loss of facial volume. Dermal fillers of hyaluronic acid replace lost tissue volume, imparting a full and youthful appearance to skin that has lost its elasticity. Hyaluronic acid fillers contain cross-linked hyaluronic acid particles, rendering a concentrated substance with resistance to various forms of physical and chemical breakdown. The cosmetic benefits of hyaluronic acid filler may last up to 6 months, depending on the brand and technique used for injection. Additionally, dermal hyaluronic acid fillers are known to increase the production of fibroblasts, supporting wound healing and offering relief from irritating and inflammatory skin conditions.
Hyaluronic acid for joint pain
Most cells in the human body are capable of synthesizing HA. It is a primary component of the extracellular matrix (ECM) and can be found in bone marrow, cartilage, and synovial fluid in joints. In osteoarthritis, the concentration of naturally occurring hyaluronic acid gradually decreases, lowering the viscosity of synovial fluid that protects joints from excess friction. Administration of intra-articular hyaluronic acid increases viscosity of synovial joint fluid, reducing friction and subsequently relieving painful arthritic symptoms.
Hyaluronic acid for ophthalmic conditions and ophthalmological procedures
Solutions of hyaluronic acid with a concentration greater than 0.1% moisturize the surface of the eyes to treat symptoms of dry eye while improving the stabilization of tear film, replenishing deficiencies of HA, reducing friction, and preventing binding of foreign substances to the ocular tissue. Hyaluronic acid is frequently used during and after ophthalmological surgeries and plays important roles by virtue of its moisturizing, viscoelastic, and protective properties. It promotes tissue healing of the corneal epithelium and other parts of the eye following ophthalmological surgery, minimizing the risk of adhesions and free radical formation.
Toxicity
In an acute oral toxicity study, the LD50-value for β-arbutin is 9804 mg/kg bw for the mouse and 8715 mg/kg bw for the rat . Dermal LD50 value in rat and mouse was reported to be greater than 928 mg/kg bw, according to an acute dermal toxicity study . Extremely high doses may cause ringing in the ears, shortness of breath, convulsions, collapse, vomiting and delirium . Nausea and vomiting were seen individuals with sensitive stomachs following oral ingestion of 15 g of dried uva ursi leaves that contain arbutin .
The oral LD50 of the sodium salt of hyaluronic acid is >800 mg/kg in the rat. Overdose information is not readily available in the literature. The safety profile for hyaluronic acid favourable, however, single case reports of death following vaginal injection of hyaluronic acid are published; the deaths likely occurred due to poor procedure regulation.
Volume of Distribution
No pharmacokinetic data available.
There is limited information in the literature regarding the human pharmacokinetics of hyaluronic acid. After a dermal filler injection, HA distributes rapidly into the superficial and deep dermis. Hyaluronic acid is distributed to skin of rats after intestinal metabolism into oligosaccharides. In rats and beagle dogs receiving oral hyaluronic acid, HA accumulated in the thyroid gland, kidneys, bladder, and stomach. HA was found to be concentrated in the vertebrae, joints, and salivary glands within 4 hours after a single dose. It is suggested by pharmacokinetic studies in animals that HA distributes into the lymphatic system.
Elimination Route
Arbutin was found to be extensively absorbed from the gastrointestinal tract where it is primarily converted to hydroquinone .
There is limited information in the literature regarding the human absorption and pharmacokinetics of hyaluronic acid. When administered to rats in the oral form, hyaluronic acid is broken down to oligosaccharides by intestinal bacteria and absorbed in the colon. In pharmacokinetic studies of beagle dogs, HA was readily absorbed and rapidly excreted. When applied topically, HA with low molecular weight ranging from 20-300 kDa is absorbed through the stratum corneum, and HA with high molecular weight (1000-1400 kDa) does not penetrate the stratum corneum. The bioavailability of hyaluronic acid depends on its molecular weight.
Half Life
No pharmacokinetic data available.
When injected by the intra-articular route hyaluronic acid has a half-life ranging from 17 hours to 1.5 days. The half-life of hyaluronic acid is longer for purified or formulations or preparations with high molecular weight. It can vary according to the molecular weight of the administered HA, according to studies in animals. The metabolic half-life of hyaluronic acid in sheep was determined to be approximately 27 hours in pharmacokinetic studies. In sheep, HA is believed to undergo rapid elimination via the blood and liver.
Clearance
No pharmacokinetic data available.
There is limited information in the literature regarding the human pharmacokinetics of hyaluronic acid. In a pharmacokinetic study of rabbits, maximum clearance capacity of intravenously administered hyaluronic acid was about 30 mg/day/kg.
Elimination Route
During the first 4 hours following ingestion of a single dose of 210 mg arbutin in healthy volunteers, 224.5 μmol/L hydroquinone glucuronide and 182 μmol/L of hydroquinone sulfate were recovered in the urine .
There is limited information in the literature regarding the human pharmacokinetics of hyaluronic acid. Studies in rats and dogs administered a radio-labeled oral dose of HA showed 87-96% excretion the feces. Excretion of hyaluronic acid is primarily extra-renal, with some contribution from the spleen.
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