247 results about "Skin permeability" patented technology

The invention belongs to the technical field of biological medicine, and particularly relates to a luliconazole composition containing essential oil, cream and a preparation method and application of the luliconazole composition. The present application provides a composition containing tea tree essential oil that promotes the skin permeability of luliconazole and has an antibacterial function, the tea tree essential oil and luliconazole form a synergistic antifungal effect, the transdermal absorption is enhanced by a natural terpene component, and the irritation to the skin is significantly reduced.

The present invention addresses the problem of providing an improving agent for improving a stratum corneum barrier function without external replenishment with any moisturizing substance and a pharmaceutical composition containing said improving agent. The present invention provides: a stratum corneum barrier function improving agent which contains a glycolytic inhibitor as an active ingredient; the stratum corneum barrier function improving agent in which the glycolytic inhibitor is at least one selected from the group consisting of a glucose transporter inhibitor and a glucose competitive inhibitor; either of said stratum corneum barrier function improving agents having at least one selected from the group consisting of an inhibitory effect on the loss of skin moisture retention capacity and an inhibitory effect on skin permeability enhancement; and a pharmaceutical composition which contains any of said stratum corneum barrier function improving agents.

The invention provides a sustained-release microneedle for treating ill-conditioned pregnancy and a preparation method and application thereof, and relates to the technical field of biological medicines.The sustained-release microneedle for treating ill-conditioned pregnancy comprises a base and a needle tip on the base, the needle tip part of the gel microneedle is made of heparin medicine, and the needle tip part of the gel microneedle is made of gelatin. The heparin medicine comprises heparin, heparin sodium, low-molecular heparin, low-molecular heparin sodium or low-molecular heparin calcium; the needle point part comprises a heparin photo-crosslinking monomer, and the base comprises a biocompatible polymer matrix. The sustained-release microneedle for treating pathological pregnancy provided by the embodiment of the invention has good mechanical strength, skin permeability and anticoagulant activity, can reduce skin bruises caused by subcutaneous injection of heparin, improves abortion caused by infection and inflammation and abortion caused by APS (anti-phospholipid antibody syndrome), can realize sustained release of drugs and increase of drug loading capacity, and has good application prospects. Sustainable drug delivery is achieved, and frequent injection is avoided.

The invention relates to the technical field of pharmaceutical preparations, and provides a minoxidil film coating agent as well as a preparation method and application thereof. The minoxidil film coating agent provided by the invention comprises 40-60% of propylene glycol, 3-7% of polyvinyl alcohol, 20-30% of ethanol, 1-7% of minoxidil and the balance of water. According to the invention, propylene glycol is taken as a solvent, a plasticizer and a transdermal absorption enhancer, polyvinyl alcohol is taken as a film-forming material, and ethanol is taken as a volatile agent, after administration, ethanol is volatilized to promote film formation of polyvinyl alcohol, and propylene glycol enhances the plasticity of the formed film, so that the effect of reducing liquid medicine loss is achieved, the local medicine concentration is increased, and the bioavailability is improved. The minoxidil liniment disclosed by the invention has excellent skin permeability, can effectively convey a medicine to a required part, and can ensure that the medicine is released at a fixed position of the skin and is accurately administered in a medicine release process, so that the stimulation of liquid medicine flow to other parts is reduced, and a good treatment effect is achieved.

The invention discloses a method for screening potential efficacy raw materials of cosmetics by establishing a mathematical model based on molecular docking and physical and chemical properties of substances, and the method comprises the following steps: S1, aiming at semi-flexible molecular docking of a specific efficacy target, including pretreatment and simulated docking of a compound ligand and a target receptor; s2, querying and selecting cosmetic application related indexes in a database, wherein the specific indexes are molecular weight, the number of hydrogen bond receptors and donors, fat-water distribution coefficient, topological polar surface area and skin permeability; and S3, alternative compound screening, including data preprocessing, definition of optimal / inferior values and median values, primary screening of principal component analysis, weight coefficient determination by an entropy weight method and Topsis comprehensive evaluation. According to the method, reasonable non-experimental type indexes are found, so that the screening efficiency is effectively improved, the cost is effectively reduced, the scientific large-batch raw material screening requirement can be met, and besides the screening purpose, the potential size of alternative compounds can be predicted and quantified.

The invention provides transdermal recombinant keratin as well as a preparation method and application thereof, and relates to the technical field of genetic engineering. The transdermal recombinant keratin comprises a recombinant keratin and a cell penetrating peptide; the transdermal recombinant keratin has cell adhesion activity and transdermal property. The transdermal recombinant keratin comprises any one amino acid sequence as shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3 and SEQ ID NO.4 or consists of the amino acid sequence as shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3 and SEQ ID NO.4. According to the transdermal recombinant keratin, the transdermal performance and the cell adhesion activity of keratin are remarkably improved, and the problem that traditional recombinant keratin is poor in skin permeability is solved.

The invention belongs to the field of cosmetics, and particularly discloses an ormosia henryi bark extract-containing composition capable of nourishing, repairing and brightening skin as well as a preparation method and application of the composition. The composition comprises an active component, a solubilizer, polyol, phospholipid and water, wherein the active ingredients comprise an ormosia henryi bark extract, acetylchitosamine, decarboxylated carnosine or salt thereof and a coast pine bark extract. Active ingredients in the composition are good in solubility in the composition, the composition is good in stability, good in skin permeability and good in AGEs inhibition effect, the four active ingredients including the ormosia henryi bark extract, the acetylchitosamine, the decarboxylated carnosine and the coast pine bark extract are in mutual synergistic interaction, and an excellent unexpected technical effect is achieved.

The invention belongs to the technical field of cosmetics, and particularly relates to a glabridin composite glabridin amp. The invention discloses collagen nanoparticles as well as a preparation method and application thereof. The preparation method comprises the following steps: firstly, combining glabridin and glycyrrhizic acid through a non-covalent bond to obtain a glabridin-glycyrrhizic acid eutectic structure capable of overcoming the problem of solubility of glabridin, and then coating the glabridin-glycyrrhizic acid eutectic structure with a glabridin-collagen mixed solution to obtain the glabridin composite glabridin amp. The invention relates to collagen nanoparticles. The glabridin composite glabridin amp obtained by the method disclosed by the invention; the collagen nano-particles and the glabridin are good in water solubility, simple in component, high in stability and free of excessive allergy risks, the skin permeability of the glabridin, the collagen and the glabridin can be improved, the collagen, the glabridin and the glabridin are in synergistic interaction, and the utilization degree is improved.

The invention belongs to the technical field of supramolecules, and discloses a supramolecule constructed by quercetin and ergothioneine as well as a preparation method and application of the supramolecule. The preparation method of the supramolecule constructed by quercetin and ergothioneine comprises the following steps: respectively dissolving quercetin and ergothioneine in a solvent to obtain a quercetin solution and an ergothioneine solution; the preparation method comprises the following steps: adding an ergothioneine solution into a quercetin solution in an inert atmosphere, mixing, carrying out an ionizing salt formation reaction under a heating condition, concentrating, distilling, crystallizing, filtering, washing and drying to obtain the supramolecule constructed by quercetin and ergothioneine. According to the invention, quercetin is taken as an anion precursor, ergothioneine is taken as a cation precursor, the supramolecular quercetin-ergothioneine is synthesized through ionizing salt formation reaction, the supramolecular quercetin-ergothioneine has excellent biocompatibility, solubility, skin permeability and high bioavailability, a host molecular skeleton of a quercetin monomer is completely reserved, and the supramolecular quercetin-ergothioneine can be used for preparing the supramolecular quercetin-ergothioneine. Meanwhile, the quercetin and ergothioneine compound has biological activity and effects of quercetin and ergothioneine.

The invention discloses a compound fluralana external preparation for dogs, a preparation method and application, belongs to the technical field of veterinary drugs, and solves the problems that an existing preparation is poor in skin surface permeability, a solvent is easy to volatilize, and use experience and drug effect exertion are influenced. The preparation is prepared from the following raw materials: fluralana, moxidectin, ethyl butylacetamidopropionate and N, N-dimethylformamide. The preparation method comprises the following steps: adding N, N-dimethylacetamide, acetone, an auxiliary adjuvant, a transdermal penetration enhancer, an antioxidant and a surface film-forming agent; according to the invention, the combination of the fluralab and the moxidectin can play a synergistic effect and expand an anti-parasitic spectrum so as to achieve an internal and external driving effect; both the fluralab and the moxidectin belong to high-fat-soluble substances, parasites can be quickly repelled and killed by adding novel adjuvant natural parasite expelling ingredients, and meanwhile, the skin permeability can be improved by adding the efficient transdermal penetration enhancer, and the risk that medicine residues are licked by pets is reduced.

The invention provides a nicotine-containing gel and a preparation method thereof. The nicotine-containing gel comprises the following components: a nicotine microcapsule, a penetrant, a gel matrix, a flavoring agent and water. The gel has excellent biocompatibility and slow release performance through combination of the nicotine microcapsules and the gel matrix, the skin permeability of nicotine can be improved by adding the penetrant, and the gel has the advantages of freshening the oral cavity and keeping fragrance for a long time by adding the flavoring agent. Therefore, a new consumption choice can be provided for smoking cessation groups and patients needing nicotine medicine.

The invention discloses a supported hyaluronic acid particle, a cosmetic, a preparation method and an application. The preparation method comprises the following steps: S1, carrying out ultrasonic treatment on a hyaluronic acid aqueous solution and a cationic polymer solution, and drying to obtain powder; and S2, in the presence of a buffer solution and a cross-linking agent, carrying out a cross-linking reaction on the powder and the effective components, and carrying out ball milling to prepare the supported hyaluronic acid particles. According to the method, the surface of the hyaluronic acid is coated with the cationic polymer, the active ingredients are loaded, the loaded hyaluronic acid particles are prepared through ball milling and are in a corner angle shape, the skin permeability can be remarkably improved, the stability of the loaded active ingredients is improved, and meanwhile the dual effects of moisturizing and skin barrier strengthening of the hyaluronic acid are achieved. According to the cosmetic containing the supported hyaluronic acid particles, the active ingredients can stably exist under various conditions, and the activity can maintain the stability for a long time.

The invention relates to a sinomenine hydrochloride loaded chlorcosan polysaccharide microneedle as well as a preparation method and application thereof, and belongs to the technical field of sinomenine hydrochloride microneedles. The chlorpeas polysaccharide microneedle comprises a needle tip layer and a backing layer, the needle tip layer is prepared by performing primary drying on a mixed aqueous solution containing sinomenine hydrochloride and chlorpeas polysaccharide, and the backing layer is prepared by performing secondary drying on a chlorpeas polysaccharide aqueous solution. The sinomenine hydrochloride loaded Jingui bean polysaccharide microneedle has enough mechanical strength to penetrate through the stratum corneum, has biodegradability and good biocompatibility, is small in skin irritation, has good skin permeability and high drug loading capacity, and has flexibility and adhesion due to the fact that the microneedle is backed. When in use, the micro-needle can be tightly adhered to a movable joint part, so that dissolution is promoted, the insertion efficiency of the micro-needle is improved, and the stability of transdermal drug delivery is ensured.

The invention belongs to the field of skin care and skin disease treatment, and provides a skin care composition and application thereof, and the skin care composition is in a liquid form and comprises recombinant collagen and glycolic acid. The specific low-concentration glycolic acid in the skin care composition disclosed by the invention ensures the mild keratin metabolism capability; the recombinant collagen with high transdermal property can quickly permeate into the deep layer of the skin, and can immediately provide a repairing raw material for the skin while the glycolic acid acts, so that discomforts such as redness and stabbing pain are remarkably relieved, and synchronous skin care and repairing is realized.

This invention belongs to the field of cosmetic technology, specifically a glycyrrhizin-based composite nanoparticle containing sclerotherapy, BPOXY, and collagen, along with its preparation method and applications. The invention first combines glycyrrhizin and glycyrrhizic acid via non-covalent bonds to obtain a glycyrrhizin-glycyrrhizic acid eutectic structure that overcomes the solubility problem of glycyrrhizin. Then, a BPOXY-collagen mixture is used to coat the glycyrrhizin-glycyrrhizic acid eutectic structure, yielding glycyrrhizin-based composite nanoparticles containing sclerotherapy, BPOXY, and collagen. The glycyrrhizin-based composite nanoparticles containing sclerotherapy, BPOXY, and collagen obtained using this method exhibit good water solubility of glycyrrhizin, a simple composition, high stability, and minimal risk of allergic reactions. Furthermore, it enhances the skin permeability of glycyrrhizin, collagen, and BPOXY, resulting in a synergistic effect and improved bioavailability.

The invention belongs to the technical field of biological medicine, and particularly relates to hyaluronic acid nano-microspheres as well as a preparation method and application thereof. According to the preparation method of the hyaluronic acid nano-microspheres, the hyaluronic acid nano-microspheres are prepared through interaction of nucleic acid, basic amino acid and hyaluronate in a specific proportion, the preparation process is optimized, and the prepared hyaluronic acid nano-microspheres are high in hyaluronic acid adding amount, high in skin permeability and good in skin care effect. The stability is good, and the application requirements in transdermal drug delivery drugs, skin care products and other products are met. Meanwhile, a non-covalent binding mode is adopted for preparing the nano-microspheres, the preparation operation is simple, the gelling property of the hyaluronate is effectively improved, the sticky feeling under high content is improved, and the application scene of hyaluronic acid in the field of skin care products is widened.

The invention discloses a preparation method of anti-aging whitening skin cream based on traditional Chinese medicine exosome extraction, and relates to the technical field of cosmetics. Comprising the following steps: (1) raw material compatibility and pretreatment: taking 1-8 parts by mass of abelmoschus manihot exosome, 1-8 parts by mass of bighead atractylodes rhizome exosome, 1-8 parts by mass of bletilla striata exosome, 1-8 parts by mass of radix angelicae exosome, 1-8 parts by mass of white poria cocos exosome, 1-8 parts by mass of radix paeoniae alba exosome, 1-8 parts by mass of lily exosome, 1-8 parts by mass of silkworm larva exosome, 1-8 parts by mass of white asarum exosome and 1-8 parts by mass of cordyceps sinensis exosome; according to the skin care product disclosed by the invention, the exosome system of twelve traditional Chinese medicinal materials is applied to the field of skin care products for the first time; a complete traditional Chinese medicine exosome extraction, identification and preparation technology system is established; the exosome is used as a natural nano-carrier, so that the skin permeability of active ingredients is remarkably improved; based on the theory of complementing color with color in traditional Chinese medicine, traditional Chinese medicinal materials with white character heads are carefully selected; the exosomes of the medicinal materials have a synergistic effect, so that multi-target skin metabolism regulation is realized.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a marine small molecule peptide and an active variant thereof in preparation of a medicine for treating skin diseases, the marine small molecule peptide and the active variant thereof can effectively inhibit keratinocyte pan apoptosis induced by TNF-alpha and IFN-gamma, the formation of a PANoptosome complex is blocked through a multi-target synergistic effect, and the effect of treating the skin diseases is achieved. The oxidative stress is reduced, and mitochondria is stabilized, so that a skin inflammatory cell death network is inhibited from the source. The variant has the same high sequence as the peptide, retains the activity of inhibiting cell pan-apoptosis, and has enhanced stability, skin permeability, in vivo half-life or efficacy. Based on the action mechanism, the peptide and the variant thereof can be used for preparing medicines for preventing and treating intractable skin diseases such as epidermis necrolysis, psoriasis, atopic dermatitis, skin lupus erythematosus and lichen planus. The invention also provides a composition containing the peptide or the variant thereof, and dosage forms comprise an external preparation and an injection.

The topical composition is for application to a portion of skin at a locus of postsurgical pain and comprises: an amount of anti-inflammatory analgesic; an amount of muscle relaxant; an amount of neuropathic analgesic; an amount of anesthetic; and a carrier having skin penetration enhancement qualities.

The present application provides a glabridin composition with high skin permeability and a preparation method and use thereof, belonging to the field of cosmetics. The glabridin composition is prepared from an S1 phase, an S2 phase and an S3 phase, in which the S1 phase consists of an oil and glabridin, the S2 phase is prepared from 3-o-ethyl ascorbic acid, an anionic surfactant, a nonionic surfactant, a polyol and water, and the S3 phase is water. The glabridin composition is prepared by conventional emulsifying equipment, and has low preparation cost, and simple operation process. The composition has good skin permeability, and has good state stability, good content stability, good pH stability and high mildness under high temperature and low temperature conditions, thus having unexpected technical effects.

The invention provides a dual ceramide essence inclusion. The dual ceramide essence inclusion is prepared from the following components in parts by weight: 1-6 parts of an active ingredient, 2-8 parts of an amphiphilic inclusion material and 40-70 parts of a microbe-derived vesicle material, wherein the active ingredients comprise ceramide NS / ceramide NG and ceramide AS; the amphiphilic inclusion material comprises the active component to form nanoparticles; the nanoparticle is wrapped by the microbe-derived vesicle material to form a ceramide / amphiphilic inclusion material / vesicle compound. The invention further provides a preparation method and application of the dual ceramide essence inclusion. The dual ceramide essence inclusion provided by the invention is high in stability and good in skin permeability, and has good repairing and anti-aging effects.

A subject matter of the present disclosure is to a cosmetic capable of increasing the skin permeability of imidazolidinone derivatives and their salts.A cosmetic of the present disclosure comprises at least one water-soluble agent selected from the group consisting of an imidazolidinone derivative of the following Formula 1:(wherein in Formula 1, R1 and R2 are each independently a hydrogen atom, a C1 to C4 linear or branched alkyl group having 0 to 3 hydroxyl groups, or a C3 to C7 cycloalkyl group having 0 to 5 hydroxyl groups)and a salt thereof; and at least one surfactant selected from the group consisting of an amino acid surfactant and a taurine surfactant.

The invention discloses infantile massage oil with the effects of strengthening the spleen and nourishing the stomach and a preparation method thereof. The infantile massage oil with the effects of strengthening the spleen and nourishing the stomach is prepared from the following raw materials in parts by weight: 8 to 12 parts of fructus evodiae, 8 to 12 parts of radix aucklandiae, 8 to 12 parts of fried malt, 8 to 12 parts of rhizoma atractylodis, 4 to 8 parts of fried semen raphani, 15 to 25 parts of fructus amomi and 3 to 7 parts of fried endothelium corneum gigeriae galli. According to the infantile massage oil with the spleen-tonifying and stomach-nourishing effects, the working principles that the skin permeability is high, the medicine can be absorbed percutaneously, the medicine metabolism is fast, retention is avoided, the medicine can easily pass through a blood brain barrier, and the medicine effect can enter meridians and collaterals are utilized; through a three-in-one scheme of'compound compatibility design-carrier synergism-low-sensitivity matrix optimization ', the effects of tonifying the spleen and nourishing the stomach are achieved, the effect is good, and the effect taking speed is high.

The invention provides a glabridin micro-emulsion, a glabridin micro-emulsion mask liquid and a preparation method, and relates to the technical field of cosmetics. The glabridin microemulsion provided by the invention is prepared from the following raw materials: glabridin, tween-80, 1, 2-hexanediol, ethyl oleate and water, and the mass ratio of the glabridin to the tween-80 to the 1, 2-hexanediol to the ethyl oleate to the water is (0.25 to 2.5) to (12.5 to 25) to (12.5 to 50) to (5 to 12.5) to 19. According to the glabridin microemulsion, 1, 2-hexanediol is used as a surfactant, tween-80 is used as a cosurfactant, ethyl oleate is used as an oil phase, glabridin is wrapped in the microemulsion, the solubility and skin permeability of glabridin can be improved, and cosmetics can efficiently play skin care functions such as whitening and relieving. The invention provides a glabridin micro-emulsion mask liquid which has good whitening, moisturizing and soothing effects.

The invention relates to a ginsenoside nano-micelle based on intermolecular self-assembly as well as a preparation method and application thereof, and belongs to the technical field of nano-micelles. The preparation process of the ginsenoside nano-micelle comprises the following steps: converting raw materials of panaxadiol saponin by using a compound enzyme, removing impurities by passing through a column, carrying out intermolecular self-assembly under ultrasonic, and purifying; the ginsenoside nano-micelle is prepared from ginsenoside Rg5, ginsenoside CK and ginsenoside Rg3, and the ginsenoside Rg5, the ginsenoside CK and the ginsenoside Rg3 are used as auxiliary materials. The ginsenoside nano-micelle is prepared in an intermolecular self-assembly mode, the water solubility and stability of ginsenoside are remarkably improved, the ginsenoside can be uniformly dispersed in a water solution and is not prone to precipitation and degradation, meanwhile, the skin permeability of the ginsenoside can be effectively improved through the nanoscale micelle structure, and the skin permeability of the ginsenoside can be effectively improved. Therefore, the skin care effect of the ginsenoside is fully exerted, and the ginsenoside is very suitable for being applied to skin care products.

The invention discloses a portable hot compress medicine carrying device for treating temporomandibular arthropathy, which comprises a main body part provided with a placing cavity; the medicine carrying assembly is arranged in the placing cavity; the ear hook is connected to the side of the main body part so as to be hung on the ear, so that the medicine carrying assembly faces the temporomandibular joint; the medicine carrying assembly comprises a medicine box, a sponge layer and a graphene heating layer, the sponge layer is arranged between the medicine box and the graphene heating layer, and liquid medicine in the medicine box is conveyed to the graphene heating layer arranged towards the temporomandibular joint through the sponge layer; the graphene heating layer is electrified to emit far infrared waves, so that blood circulation of the temporomandibular joint area is promoted through heat radiation, and percutaneous release of liquid medicine is enhanced. According to the medicine carrying device, through heat radiation of the graphene heating layer, local blood circulation of the temporomandibular joint is improved, skin permeability is improved, and medicine penetrates through the skin to enter subcutaneous tissue or muscular tissue.

The invention relates to a brightening composition for improving skin transparency and glossiness and application of the brightening composition, and belongs to the technical field of cosmetics. The brightening composition comprises oxyresveratrol, a loquat leaf extract, a burdock seed extract and a verbascos extract, the composition can effectively resist oxidation and inflammation through the oxyresveratrol so as to relieve skin darkness, and the loquat leaf extract can promote cell autophagy so as to remove metabolic waste and improve skin permeability. The burdock seed extract improves the epidermis structure so as to enhance the skin light transmission, and the verbascos extract plays a role in instant brightening through a quantum transition effect. According to the composition, through the synergistic effect of all the components, the skin transparency and glossiness are remarkably improved, and the composition is mild, free of irritation and suitable for being used by people with sensitive skin.

This invention provides a Panax notoginseng-Paris polyphylla supramolecular complex, its preparation method, cosmetic products, and applications. The Panax notoginseng-Paris polyphylla supramolecular complex is a complex formed by non-covalent bonding of Panax notoginseng extract (as the host molecule) and Paris polyphylla extract (as the guest molecule), with the host molecule encapsulating the guest molecule structure. The Panax notoginseng-Paris polyphylla supramolecular complex of this invention not only improves the water solubility of Paris polyphylla extract but also increases its skin permeability and reduces its cytotoxicity. The preparation method of this invention utilizes the synergistic effect of the active ingredients, resulting in strong compatibility and synergistic efficacy. It also slows down the release time of the active ingredients, extends their shelf life, and features a simple and easy-to-control process, stable granulation effect, and low production cost.

The invention provides a nano-emulsion composition, a nano skin care product, a preparation method and application, the nano-emulsion composition comprises a nano-emulsion and nucleic acid loaded on the surface of the nano-emulsion, and the nano-emulsion comprises a functional component, an emulsifier, an emollient, an antioxidant, a humectant and water; the functional component comprises a barrier repair lipid, the barrier repair lipid comprises sphingolipid, the sphingolipid comprises phytosphingosine, and the barrier repair lipid further comprises one or more of ceramide, free fatty acid and cholesterol; the mass ratio of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%. The nanoemulsion composition has excellent permeability, so that the skin permeability of the nucleic acid is improved, and the bioavailability of the nucleic acid is improved; meanwhile, the nucleic acid can be specifically bound with adenosine A2A receptors distributed on keratinocytes, so that the binding speed of the nano-emulsion and the cells can be increased, the absorption and action effects of the nano-emulsion are specifically promoted, and the resistance of the skin to light aging is improved.

An iontophoresis device capable of reducing skin irritability due to an applied current while enhancing skin permeability of a drug is provided. The iontophoresis device includes a power supply, an electrode electrically connected to the power supply, a drug disposed between skin and the electrode, and a control unit configured to control a current applied to the skin via the electrode. The control unit controls the current so that a pulse current having a pulse frequency of 0.5 Hz or more and 50 Hz or less is applied to the skin.