68 results about "Disodium Edetate" patented technology

The invention belongs to the field of pharmaceutical preparations, and particularly relates to nitrogen hydrochloride # imgabs0 # stine eye drops and a preparation process thereof, the nitrogen hydrochloride # imgabs0 # stine eye drops comprise 0.05% of nitrogen hydrochloride # imgabs1 # stine, 0.2-0.3% of hydroxypropyl methylcellulose, 0.1-0.2% of edetate disodium, 0.12-0.15% of an isoosmotic adjusting agent, 0.04-0.07% of a preservative and 0.005-0.0075% of choline aromatic folic acid; the nitrogen hydrochloride # imgabs2 # stine eye drops prepared by the preparation method disclosed by the invention have the advantages that the adsorption of nitrogen hydrochloride # imgabs3 # stine on a low-density polyethylene bottle is well inhibited under the condition of visible light, and the reduction of the concentration of nitrogen hydrochloride # imgabs4 # stine in the eye drops is remarkably prevented, so that the medication safety is improved. Besides, the added cholinofolic acid and hydroxypropyl methylcellulose have small irritation to eyes under a specific ratio, and can also have a large enough contact angle with the eyes of rabbits at high temperature, so that the retention property of the eye drops on the eyes can be improved, and the drug effect can be favorably exerted.

The invention discloses a composition and a preparation method of a single-dose vitamin B12 eye drop without a bacteriostatic agent, and the single-dose vitamin B12 eye drop without the bacteriostatic agent is prepared from vitamin B12, a buffering agent, sodium hyaluronate, edetate disodium and water for injection. According to the vitamin B12 eye drops and the preparation method thereof disclosed by the invention, the vitamin B12 eye drops are produced by adopting a totally-closed sterile filling process, and a disposable single-dose packaging container is arranged, so that the sterility of medicines is ensured, and meanwhile, the use safety, the operation convenience index and the safety performance are improved.

The invention relates to a dexamethasone sodium phosphate injection and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The preparation method comprises the following steps: 1, sequentially adding glycerol, edetate disodium and dexamethasone sodium phosphate into water for injection according to a weight ratio of (20-25): (0.08-0.12): (4-6), mixing and dissolving, and introducing nitrogen until the dissolved oxygen content is less than or equal to 1mg / L to obtain a liquid medicine 1; step 2, adding a pH regulator into the liquid medicine 1 to regulate the pH value to 7.0-8.5 to obtain liquid medicine 2; and step 3, filtering, filling and sealing the liquid medicine 2, and controlling the residual oxygen content to be less than or equal to 5% to obtain the dexamethasone sodium phosphate injection. Wherein the whole preparation process is protected by inert gas. According to the preparation method of the dexamethasone sodium phosphate injection provided by the invention, the prescription composition of an original drug does not need to be changed, and the prepared dexamethasone sodium phosphate injection can be stably stored at room temperature by adjusting a specific pH range, keeping filling of an inactive gas until the dissolved oxygen content is less than or equal to 1mg / L in the whole preparation process and controlling the residual oxygen content to be less than or equal to 5%.

The invention discloses a preparation for treating psoriasis and application. The preparation is prepared from the following raw materials: propylene glycol, halcinonide, fluocinonide acetate, salicylic acid, dimethyl sulfoxide, polyethylene glycol 400, glycerol, borneol, edetate disodium, ethylparaben and ethylparaben. The traditional Chinese medicine composition is reasonable in composition, the treatment effect on psoriasis can be remarkably improved, the problem of pigmentation after treatment can be effectively improved or avoided, and particularly, due to the use of salicylic acid and edetate disodium, it is verified that the traditional Chinese medicine composition has a remarkable curative effect on psoriasis. Salicylic acid and edetate disodium have a synergistic effect on psoriasis treatment effect and pigmentation improvement of the whole medicine system.

This invention discloses a carbetocin injection solution and its preparation process. The raw materials for the carbetocin injection solution include at least carbetocin, methionine, disodium edetate, an antibacterial agent, a pH adjuster, and a solvent. The pH of the carbetocin injection solution is 4.0-4.5. The concentration of carbetocin is 50 μg / ml-80 μg / ml, the concentration of methionine is 10 mg / ml-20 mg / ml, the concentration of disodium edetate is 5 mg / ml-10 mg / ml, and the concentration of the antibacterial agent is 2 mg / ml-3 mg / ml. By controlling the concentrations of carbetocin, methionine, disodium edetate, and the antibacterial agent, and simultaneously adjusting the pH of the injection solution to 4.0-4.5, this invention eliminates the need for nitrogen purging during the preparation process, thereby enabling the prepared carbetocin injection solution to exhibit high antioxidant properties and stability, allowing for long-term storage at room temperature.

The invention relates to the technical field of medical supplies, and particularly provides an NMN-containing circulation promoting and skin aging resisting repair patch which comprises a repair liquid and a non-woven fabric, the repairing liquid is prepared from the following raw materials in percentage by weight: 0.2 to 0.5 percent of sodium hyaluronate, 0.01 to 0.2 percent of beta-nicotinamide mononucleotide (NMN), 2 to 4 percent of glycerol, 0.5 to 1.5 percent of propylene glycol, 0.005 to 0.015 percent of ethylene diamine tetraacetic acid disodium salt, 0.015 to 0.03 percent of ethylparaben, 1 to 2 percent of sodium carboxymethyl cellulose, 0.05 to 2.0 percent of triethanolamine and the balance of purified water. The repair patch has good moisture retention, stability and oxygen permeability, and is small in irritation.

The invention belongs to the technical field of pharmacy, and particularly relates to amorolfine hydrochloride cream and a preparation method thereof. The amorolfine hydrochloride emulsifiable paste is prepared from the following raw materials: amorolfine hydrochloride, octadecanol, white vaseline, modified liquid paraffin, polyoxyl (40) stearate, phenoxyethanol, edetate disodium, carbomer homopolymer type B, sodium hydroxide and water. The modified liquid paraffin is added into the amorolfine hydrochloride emulsifiable paste, so that on one hand, the modified liquid paraffin and the active ingredients of the amorolfine hydrochloride emulsifiable paste have a synergistic effect, the structure and the function of fungi are destroyed, and the death of fungal cells is accelerated; on the other hand, the amorolfine hydrochloride emulsifiable paste can inhibit respiration of corresponding enzymes through water locking, energy synthesis is blocked, and fungus growth is inhibited. After the amorolfine hydrochloride emulsifiable paste is prepared by combining the preparation method provided by the invention, the stability of the amorolfine hydrochloride is good, the uniform release of effective components of the amorolfine hydrochloride is promoted, and a scientific basis is provided for preventing and treating fungi.

The invention relates to a lornoxicam freeze-dried preparation for injection and a preparation method of the lornoxicam freeze-dried preparation, and belongs to the technical field of pharmaceutical preparations. The preparation method of the freeze-dried preparation comprises the following steps: step 1, sequentially adding edetate disodium, mannitol and tromethamine into water at 53-65 DEG C, and mixing and dissolving to obtain a mixed solution A; 2, adding lornoxicam into the mixed solution A at 53-65 DEG C, and dissolving to obtain a mixed solution B; and step 3, filtering the mixed solution B to obtain the lornoxicam freeze-dried preparation. According to the preparation method of the lornoxicam freeze-dried preparation for injection, auxiliary materials do not need to be changed, and the lornoxicam freeze-dried preparation which is good in solubility, low in impurity content, good in redissolution clarity and stable can be obtained only through the specific liquid preparation temperature.

The invention discloses an adapalene gel preparation method, which comprises: 1) preparing a carbomer phase: mixing a first solution and a second solution to obtain a mixed solution, and adding carbomer into the mixed solution, the first solution being obtained by mixing edetate disodium and water, the second solution being obtained by mixing edetate disodium and water, and the first solution being obtained by mixing edetate disodium and water; the second solution is obtained by mixing phenoxyethanol, methylparaben and propylene glycol; 2) preparation of adapalene phase: adding water into poloxamer to obtain a solution, and then adding adapalene into the solution; and 3) total mixing: mixing the adapalene phase and the carbomer phase while stirring to obtain a gel precursor, and then degassing, filling and sealing the gel precursor.

The invention discloses a rifapentine isoniazide tablet and a preparation method thereof, the rifapentine isoniazide tablet is a core-coated tablet, and comprises an inner-layer tablet core containing rifapentine and an outer-layer tablet layer containing isoniazide; the inner-layer tablet core comprises rifapentine, edetate disodium, sodium ascorbate and lauryl sodium sulfate, the rifapentine accounts for 53-63% of the total mass of the inner-layer tablet core, and the rifapentine tablet further comprises a filler, a stabilizer, a disintegrating agent, an adhesive, a surfactant, a lubricant and a coating layer; the coating layer coats the inner-layer tablet core; the outer sheet layer comprises isoniazide, a filling agent, a disintegrating agent, an adhesive, a lubricant and an adhesive; and the mass of the isoniazide accounts for 75-95% of the total mass of the outer sheet layer. According to the rifapentine isoniazide tablet disclosed by the invention, the compliance of a patient is enhanced. And meanwhile, the potential safety hazard problem of impurity increase caused by incompatibility of rifapentine and isoniazide is solved.

The present invention relates to a method for alleviating asthenopia and a liquid composition for ophthalmic use. Specifically, on one hand, the invention relates to a liquid composition for eyes. The invention relates to a skin-care lotion, which is prepared from the following components: glycerol, p-hydroxyacetophenone, sodium hyaluronate, propylene glycol, menthol, borneol, methyl diisopropyl propionamide, menthol, SOLUBILISANT LRI, edetate disodium, water-locking magnetite, radix gentianae extract, totarol, sodium citrate, ectodoine, ergothioneine, hydrolyzed red algae extract and water. Furthermore, the invention also relates to an application of the liquid composition in preparation of a product for relieving eye asthenopia for eye use. The liquid composition of the present invention exhibits excellent properties, for example as described in the specification.

The present invention provides a lomefloxacin hydrochloride ear drop composition, its product, preparation method and application, relating to the technical field of pharmaceutical preparations. The lomefloxacin hydrochloride ear drop composition of the present invention is prepared from the following raw materials in parts by weight: 3.0 - 6.7 parts of lomefloxacin hydrochloride, 30 - 50 parts of polyethylene glycol 200 - 300, 20 - 40 parts of propylene glycol, 3 - 6 parts of hydroxypropyl cellulose, 1 - 3 parts of polyvinylpyrrolidone, 0.5 - 2 parts of sodium acetate and 0.5 - 2 parts of disodium edetate; the lomefloxacin hydrochloride ear drop composition is prepared into lomefloxacin hydrochloride ear drops by a method of stepwise heating and ultrasonic mixing. The lomefloxacin hydrochloride ear drop composition of the present invention has a fast transdermal absorption rate and can quickly exert the drug effect of lomefloxacin hydrochloride in a short time; it still has high stability under strong light conditions and has high drug safety.

This invention provides an birepiperazole oral solution, wherein the solution comprises birepiperazole 0.4-0.6 mg / ml, disodium edetate 0.1-0.5 mg / ml, methylparaben 1.5-2.0 mg / ml, propylparaben 0.15-0.25 mg / ml, an acidic pH adjuster 2.5-3.5 mg / ml, a flavoring agent 0.8-1.2 mg / ml, propylene glycol 40-60 mg / ml, glycerin 120-180 mg / ml, and a sodium hydroxide solution to adjust the pH to 2.9-3.3. The drug exhibits high stability during preparation, storage, and clinical formulation.

The invention discloses a medical gynecological gel dressing and a preparation method thereof, and relates to the technical field of medical dressings. The medical gel dressing is prepared from the following raw materials: a carbomer homopolymer, glycerol, edetate disodium, triethanolamine, a bacteriostatic agent and purified water, the preparation method of the medical gel dressing comprises a gel matrix preparation step, a mixing I step, a mixing II step, a mixing III step, a mixing IV step, a homogenizing step and a quality inspection step, the temperature is low in the material dissolving process, carbomer homopolymers are not prone to being decomposed and deteriorated, the stability of the gel structure is easily maintained, the preparation technology is simple, and the medical gel dressing is suitable for being used for preparing medical gel dressing materials. The probability of excessive swelling, degradation or local gel curing of the carbomer homopolymer can be reduced, and the biocompatibility of the gel dressing is improved.

The invention discloses a composition and a preparation method of an epinephrine hydrochloride injection, the formula comprises epinephrine, hydrochloric acid, sodium chloride (for injection), edetate disodium, L (+) tartaric acid, alpha-ketoglutaric acid, sodium hydroxide and water for injection, and the use amount of alpha-ketoglutaric acid is 0.35-0.75 mg / ml. The epinephrine hydrochloride injection disclosed by the invention is simple in composition and stable in quality, the preparation process is simple, convenient and efficient, special equipment and inert gas filling are not needed, and a filled sample is subjected to high-pressure steam sterilization under the condition of 121 DEG C / 12min.

The invention belongs to the technical field of medicine, and particularly relates to poloxamer hydrogel for treating haemorrhoids, the main component of the hydrogel is poloxamer, the content of the poloxamer is 2.5-3.5%, and the hydrogel can further contain carbomer, edetate disodium, glycerol, triethanolamine and methylparaben, and the haemorrhoids hydrogel is remarkable in curative effect, small in irritation and free of toxic and side effects. The traditional Chinese medicine composition can be used for treating symptoms such as anal falling swelling pain, mucosa hyperemia and hematochezia caused by internal hemorrhoids, external hemorrhoids and mixed hemorrhoids.

The present invention relates to the field of pharmaceutical chemicals, in particular to the synthetic method of acetylcysteine injection, comprising the steps of: 1) adding water for injection into a stainless steel preparation tank, continuing to pass through nitrogen to displace the air in the preparation tank, then adding disodium edetate at 50 55 DEG C, stirring, and obtaining a disodium edetate aqueous solution; 2) adding water for injection into another stainless steel preparation tank, continuing to pass through nitrogen to displace the air in the preparation tank, adding acetylcysteine, stirring and dissolving, using basic amino acid to adjust pH to 7.0 7.3, obtaining the acetylcysteine aqueous solution; 3) continuing to pass through nitrogen into the stainless steel preparation tank equipped with disodium edetate, the acetylcysteine aqueous solution obtained is added into the disodium edetate aqueous solution, stirring and dissolving, using basic amino acid to adjust pH to 7.0 7.3, filtering, sterilizing after canning, obtaining acetylcysteine injection. The present invention uses basic amino acid to adjust pH so that the impurities such as hydrogen sulfide in the system are significantly reduced.

The present application relates to the technical field of gynecological bacteriostatic gel, and particularly relates to a ulipristal bacteriostatic gel and a preparation method thereof; the ulipristal bacteriostatic gel comprises the following components in parts by weight: chlorhexidine acetate 1-3 parts, meihua grass extract 4-8 parts, carbomer 0.8-1.2 parts, triethanolamine 0.4-0.6 parts, penetration enhancer 0.5-1.5 parts, modified nano-silver 0.04-0.07 parts, glycerol 5-8 parts, hydrogenated polyisobutylene 0.03-0.07 parts, disodium edetate 0.1-0.3 parts and purified water in a remainder amount; the chlorhexidine acetate and the meihua grass ethanol extract are compounded at a ratio of 1:(2.5-4), the flavones and polyphenols in the meihua grass can destroy the cell membrane permeability of microorganisms, promote the chlorhexidine acetate to enter the inside of the microorganism, and significantly reduce the minimum bacteriostatic concentration.

The invention discloses a mecobalamin composition. The mecobalamin composition comprises mecobalamin, a stabilizer, a suspending aid and an adsorbent. The applicant can improve the stability of mecobalamin to a certain extent by adopting edetate disodium or citric acid as a stabilizer, and can uniformly disperse mecobalamin in the solid dispersion through spray drying to construct a physical barrier, thereby improving the light instability of mecobalamin.

A catgut implant for treating ascites and a preparation method thereof belong to the technical field of catgut preparation. Raw materials are as follows in percentage by mass: 27-31% of Gansui Banxia extract, 25-28% of humectant, 27-31% of water, 0.5-0.8% of glycyrrhizic acid, 5-9% of polyacrylic acid sodium, 1.5-4% of carboxymethyl cellulose sodium, 0.9-2.5% of polyvinylpyrrolidone, 0.03-0.06% of disodium edetate, 0.2-1.3% of organic acid, 0.5-0.9% of filling agent and 0.2-2% of transdermal penetration enhancer. The catgut implant improves the production process of catgut, reduces the production cost of catgut, has good formability and adhesion, and prepares Gansui Banxia decoction for treating ascites into catgut implant with controllable quality.

The invention relates to a revienacin inhalation solution and a preparation method thereof. The revienacin inhalation solution comprises revienacin, a stabilizing agent, a buffering agent and water for injection, wherein the stabilizer is disodium edetate and propylene glycol, and the mass volume ratio of the disodium edetate to the propylene glycol is (0.05-0.1) g: (50-300) ml. The revivin inhalation solution can effectively delay degradation of revivin under the high-temperature condition, the long-term stability of a preparation under the high-temperature condition is guaranteed, the preparation prescription and the preparation process are simple and easy to operate, and the revivin inhalation solution is suitable for large-scale industrial production.

The invention relates to a nadifloxacin emulsifiable paste and a preparation method thereof, the nadifloxacin emulsifiable paste comprises an active component nadifloxacin and pharmaceutic adjuvants, and is a water-in-oil or oil-in-water external emulsifiable paste preparation. The chemical and physical stability of the product is remarkably improved by adopting a buffer type alkaline hydrotropy system formed by sodium hydroxide and diethanol amine in a synergistic manner, an edetate disodium metal chelating agent and a specifically-formed composite oil phase matrix and combining a vacuum emulsification and double homogenization process; and the preparation process parameters are clear, the industrial amplification can be realized, and the technical problems of poor stability, large quality fluctuation, limited curative effect and the like of the existing nadifloxacin external preparation are solved.

The invention relates to sodium hyaluronate eye drops and a preparation method thereof. Every 1000 ml of the eye drops contain 1 g of sodium hyaluronate, sorbitol and nicotinamide, preferably, 2.8 g of sorbitol, 1.2 g of nicotinamide, 2 g of aminocaproic acid, 0.1 g of edetate disodium, 1.6 g of potassium chloride and 6.8 g of sodium chloride, the sodium hyaluronate eye drops prepared according to the prescription process have extremely high quality stability, the effectiveness of medication is improved, and the sodium hyaluronate eye drops are suitable for clinical application. The method is obviously superior to the prior art.

The invention belongs to the technical field of nursing products, and particularly discloses a spray for outdoor protection of infants and children and a preparation method thereof.The spray is prepared from, by mass, 1%-5% of glycerin, 0.5%-1.5% of trehalose, 0.01%-0.1% of edetate disodium, 2%-10% of a traditional Chinese medicine composition, 1%-10% of 1, 2-hexanediol, 1%-10% of 1, 2-pentanediol and the balance purified water; the preparation method of the spray comprises the following steps: S21, adding the purified water into an emulsifying pot, sequentially adding the glycerol, the trehalose, the edetate disodium and the traditional Chinese medicine composition, and then carrying out vacuum stirring and homogenizing treatment; s22, cooling, then adding 1, 2-hexanediol and 1, 2-pentanediol, and uniformly stirring; and S23, continuously cooling, keeping vacuum stirring, sieving, and discharging. According to the spray provided by the invention, the effects of preventing mosquitoes, relieving itching, repairing and relieving are provided by virtue of the traditional Chinese medicine composition, a spray type product which is easy to use is prepared by virtue of simple and common auxiliary materials, and the spray is simple in component, high in safety and good in effect.

The present invention relates to the field of pharmaceutical chemistry technology, specifically, to a crystallization process for p-aminosalicylic acid. It comprises the following steps: p-aminosalicylic acid crude product is dissolved in a solvent, disodium edetate is added synchronously to form a homogeneous solution; polyvinyl pyrrolidone and sodium lauryl sulfate are dissolved in water to form a composite micelle system, and acetone is added to form an anti-solvent phase; the anti-solvent phase is added dropwise to the homogeneous solution, and target crystal form seed is injected; the solution is subjected to solid-liquid two-phase separation; solid phase is treated to obtain wet crystals; wet crystals are processed by a vacuum belt dryer to obtain p-aminosalicylic acid crystals. In the present invention, metal-catalyzed decarboxylation is blocked by disodium edetate, free impurities are adsorbed with polyvinyl pyrrolidone-sodium lauryl sulfate micelles, and polyvinyl pyrrolidone can stabilize the target crystal lattice, and sodium lauryl sulfate can induce crystal growth, so as to stably output low residual high-purity pharmaceutical-grade p-aminosalicylic acid.

The invention relates to the field of medicine analysis and detection, in particular to a detection method and a kit for determining edetate in a liquid preparation. According to the detection method, liquid chromatography is adopted, and a mobile phase contains a derivatization reagent of edetate. The method effectively solves the problem of complex detection operation in the prior art, and has the advantages of strong specificity, wide linear range, good precision and high accuracy, and the stability of the sample to be detected is not influenced by the detection method and is only determined by the stability of the sample, so that the method is suitable for large-scale popularization and application. The content of edetate disodium in liquid preparations such as eye drops and injections can be reliably and effectively measured.

To provide a formulation that effectively sterilizes Fusobacterium within a short time.SOLUTION: A Fusobacterium-sterilizing composition contains cetylpyridinium chloride, DL-pyrrolidonecarboxylic acid salt of N-cocoyl-L-arginine ethyl ester, citric acid, and / or disodium edetate.SELECTED DRAWING: None

The invention discloses pranoprofen eye drops and a production process thereof. Comprising the following raw material components in parts by weight: 0.1 to 0.5 part of pranoprofen, 1 to 5 parts of vitamin E polyethylene glycol 1000 succinate, 2 to 6 parts of soybean phospholipid, 3 to 8 parts of polyoxyethylated castor oil EL-40, 0.1 to 0.3 part of histidine, 0.2 to 0.6 part of sodium dihydrogen phosphate, 0.3 to 0.7 part of disodium hydrogen phosphate, 2 to 5 parts of glycerol, 1 to 4 parts of polyethylene glycol 400, 0.05 to 0.2 part of sodium hyaluronate, 0.1 to 0.4 part of D-panthenol and 0.01 to 0.03 part of benzalkonium chloride. The injection comprises the following components in parts by weight: 0.05-0.15 part of potassium sorbate, 0.005-0.02 part of epsilon-polylysine, 0.01-0.05 part of edetate disodium, 0.02-0.08 part of vitamin E acetate, 0.005-0.015 part of L-cysteine and the balance of water for injection, and the total weight part of the water for injection is 100 parts. According to the invention, pranoprofen is taken as a core, and vitamin E polyethylene glycol 1000 succinate, soybean phospholipid and polyoxyethylated castor oil EL-40 are adopted for synergistic solubilization, so that the problem of poor water solubility of the medicine is solved; histidine and phosphate are compounded for buffering and are matched with multiple stabilizers, so that the stability of the preparation is improved.

The invention provides a fragrant glasses cleaning solution and a preparation method thereof, and relates to the technical field of glasses cleaning solutions. The invention relates to an antibacterial perfume, which is prepared from the following ingredients in parts by weight: 0.8 to 2 parts of fragrant microcapsules, 0.3 to 1 part of polyether modified silicone oil, 0.05 to 0.1 part of modified nano silicon dioxide, 1.5 to 3 parts of glycerinum, 0.5 to 2 parts of compound antibacterial agents, 0.3 to 0.5 part of ethylene diamine tetraacetic acid disodium salt, 8 to 12 parts of alcohols and 78 to 88 parts of deionized water. Wherein the fragrant microcapsules are prepared by wrapping essence in beta-cyclodextrin-chitosan composite microspheres, the composite antibacterial agent comprises benzalkonium chloride and polyhexamethylene biguanide in a weight ratio of (2.5-3.5): 1, and the pH value of the cleaning solution is 6-8. Through microcapsule slow release and pH control, the irritation of the cleaning liquid to eyes is reduced, and the fragrance can last for 8-10 hours; glycerin and polyether modified silicone oil have a synergistic effect, so that the antifogging time of the lens is prolonged to 72 hours, the antibacterial rate within 5 minutes can reach 99.9%, and the wear rate of 100-time coating is less than 0.1%.

The invention discloses a preparation method of clindamycin phosphate injection, and belongs to the field of pharmacy. The preparation method of the clindamycin phosphate injection comprises the following steps: sequentially and respectively dissolving the auxiliary materials edetate disodium and sodium hydroxide, then dissolving the raw material clindamycin phosphate to completely dissolve the raw material in a stable solution state, then complementing the water for injection, and carrying out multiple filter element filtration, filling, full plug pressing and capping to obtain the clindamycin phosphate injection. The clindamycin phosphate injection is obtained. The clindamycin phosphate injection obtained by the preparation method disclosed by the invention is good in quality.