Local pharmaceutical preparation composition for improving skin disease symptoms and application thereof

Abstract

The invention relates to the technical field of medicine, in particular to a local medicine preparation composition for improving skin disease symptoms and application thereof. The invention relates to a topical pharmaceutical preparation composition for improving skin disease symptoms. The topical pharmaceutical preparation composition comprises clindamycin phosphate, an echinacea extract, a solvent and a dermatologically acceptable carrier. According to the local pharmaceutical preparation composition for improving skin disease symptoms, through the synergistic effect of the clindamycin phosphate and the echinacea purpurea extract, a safer, more effective and more stable treatment scheme is provided, and a good curative effect is expected to be achieved in clinical practice.

Description

Technical Field

[0001] The present application relates to the field of medical technology, and in particular to a topical pharmaceutical preparation composition for improving symptoms of skin diseases and its application. Background Art

[0002] Clindamycin phosphate is the drug salt form of clindamycin. It has good antibacterial activity and can inhibit the growth and reproduction of many bacteria. It is often used to treat bacterial infections such as respiratory tract infections, skin and soft tissue infections, osteomyelitis, abdominal infections, and gynecological infections. Lindamycin phosphate topical solution is a very commonly used topical preparation in dermatology. After absorption, it can be hydrolyzed into clindamycin to exert an antibacterial effect. It is mainly used for the treatment of inflammatory acne and has good antibacterial activity against Propionibacterium acnes. The side effects of topical clindamycin phosphate include allergic reactions such as dry skin, sensitive irritation, skin rash, and occasional gastrointestinal reactions such as gastrointestinal discomfort. A mild and well-moisturizing moisturizer can be added to relieve the symptoms of dry skin, and ingredients that aggravate the symptoms of sensitive skin irritation should be avoided.

[0003] Acne is a common skin disease, which is mainly caused by factors such as increased sebum secretion, excessive reproduction of Corynebacterium acnes, and hyperkeratosis of hair follicle epithelium. It has been clinically proven that clindamycin phosphate has obvious effects in clearing pathogens and anti-inflammatory effects on skin acne. Common products on the market include clindamycin phosphate gel, clindamycin phosphate rub, clindamycin phosphate ointment, and clindamycin phosphate topical solution. Usually, some antioxidants, preservatives, emulsifiers and other additives can be added to maintain the stability of clindamycin phosphate drugs. The safety and compatibility of additives are particularly important.

[0004] Patent CN117653595A discloses a clindamycin phosphate topical solution, which is composed of the following components: 0.3-0.4g of clindamycin phosphate, 6-10g of isopropyl alcohol, 1-2.5g of disodium ethylenediaminetetraacetic acid, 0.1-0.2g of sesamol, 0.4-0.5g of ethanol, 0.4-0.8g of oat kernel extract, 0.03-0.05g of allantoin, and 15-25g of purified water.

[0005] CN114425035A discloses a clindamycin phosphate gel and a preparation method thereof. The raw materials are 3.5-5.2 parts of clindamycin phosphate, 1.7-3.5 parts of carbomer homopolymer, 0.5-0.9 parts of cyclic carbonate, 0.2-0.5 parts of natural nano pearl powder, 5 parts of natural nano pearl powder, 52-68 parts of auxiliary agent, 1-2 parts of pH neutralizer, 35-50 parts of cosolvent and 280-310 parts of pure water. The gel is prepared through the steps of pre-dissolution, mixed swelling and neutralization. The mixed swelling process adopts a treatment method of first fast stirring and then slow stirring.

[0006] CN116059177A discloses a clindamycin phosphate composition and its preparation method. Each 1000 vaginal effervescent tablets contain 120 grams of clindamycin phosphate, 219-255 grams of mannitol, 4.5-6.3 grams of zein, 1.5-2.7 grams of linoleic acid, 96-108 grams of tartrate, 108-120 grams of sodium bicarbonate, 12-18 grams of povidone and 3-6 grams of magnesium stearate.

[0007] CN114469857A relates to a clindamycin phosphate injection and a preparation method thereof. The injection is composed of clindamycin phosphate, benzyl alcohol, disodium ethylenediaminetetraacetate, sodium chloride, sodium hydroxide and water for injection. The preparation method comprises mixing the ingredients one by one, making a liquid in a preparation tank, and cooling the liquid to a temperature below 40°C.

[0008] CN115379837A discloses a preparation and method for transdermal administration through the skin of a subject, comprising a therapeutically effective amount of clindamycin phosphate and a permeation part, wherein the permeation part comprises: phospholipids, fatty acid esters formed from low molecular weight alcohols and long chain fatty acids.

[0009] CN114146053A discloses a composite gel for treating acne and a preparation method thereof. The composite gel comprises 1 part of clindamycin phosphate, 1.0-2.0 parts of Chinese herbal extract, 0.01-0.1 part of salicylic acid, 0.1-1 part of xanthan gum, 0.1-0.6 part of carbomer, 0.2-0.8 part of sodium benzoate, 0.01-0.8 part of disodium ethylenediaminetetraacetic acid, 0.045-0.085 part of salicylic acid, an antioxidant, 10-15 parts of glycerol, 0.1-0.5 part of polysorbate (80), 0.01-0.06 part of potassium acetate, and 2.0-3.0 parts of ethanol for clearing away heat and dampness. The composite gel further enhances the anti-inflammatory and bactericidal effects under the action of keratin dissolution, thereby treating acne more comprehensively and deeply.

[0010] CN113768866A discloses a clindamycin phosphate suppository and a preparation method thereof, which is prepared from 4-5 parts by weight of clindamycin phosphate and 55-135 parts by weight of semi-synthetic fatty acid glycerol.

[0011] CN113350273A discloses a novel clindamycin phosphate injection and its preparation method, as well as additives such as antioxidants, complexing agents, antibacterial agents and pH regulators. After mixing the components, the injection is sterilized by filtering through a microporous filter membrane to obtain a sterile injection.

[0012] CN113081975B provides a method for preparing a lyophilized powder injection of clindamycin phosphate for injection, comprising mixing injection water at a temperature of ≤25°C with clindamycin phosphate, dropping an alkali solution to raise the pH value of the system to 6.0-6.4, and obtaining the lyophilized powder injection of clindamycin phosphate for injection after decolorization, sterilization filtration and freeze drying.

[0013] CN112220738A provides a preparation composition, wherein each 10g of clindamycin phosphate gel contains 0.05-0.15g of clindamycin phosphate, 0.1-0.2g of carbomer (980NF), 0.7-1.2g of glycerol, 0.005-0.01g of methyl benzoate, 0.005-0.01g of propyl benzoate, 0.005g-0.2g of triethanolamine, and 0.01-0.02g of trachalcone.

[0014] CN112137982A provides a clindamycin phosphate tablet, which is composed of the following ingredients: 0.15g of clindamycin phosphate (calculated as clindamycin), 0.3-0.5g of lactose, 0.2-0.4g of microcrystalline cellulose, 0.005-0.01g of isomaltooligosaccharide, 0.05g-0.15g of hydroxypropyl-β-cyclodextrin, 0.005g-0.01g of magnesium stearate, and 0.01-0.02g of enteric coating powder.

[0015] Although there are a large number of patents on formulations and compositions, none of them claim that clindamycin or its salts are combined with natural extracts to promote skin health while treating acne. Acne skin requires more care due to damage, inflammation and open wounds. There are currently no reports of acne treatment formulations that can provide the care benefits of Echinacea extracts on acne skin while using clindamycin or any of its salts.

[0016] Echinacea extract is taken from the Echinacea herb and is widely used to boost the immune system and fight viruses and bacteria. It can be used as an oral supplement or topical medication. Echinacea can be used to treat certain skin conditions, including eczema and pruritus. Although there are no human trials using echinacea to treat eczema, laboratory studies have shown some positive effects of this herb. In an in vitro study (conducted in a laboratory, not on a living body), researchers found that echinacea extract reduced eczema symptoms. The researchers believe that echinacea extract has anti-inflammatory effects that deserve further study. The alkylamides in echinacea extract have strong anti-inflammatory effects and can reduce clinical symptoms of atopic eczema. In a small human trial, the potential efficacy of echinacea echinacea lotion and shampoo for pruritus (itchy skin) was investigated. Adult participants used a lotion or shampoo containing echinacea extract for four weeks. All forms of topical echinacea significantly reduced itching as well as other parameters, including dry skin.

[0017] Echinacea has been used for centuries to treat pain and inflammation. Echinacea can reduce pro-inflammatory cytokines (substances secreted by immune cells) and increase anti-inflammatory cytokines. This may be particularly helpful for cytokine storms, which are conditions in which pro-inflammatory cytokines are rapidly released due to an infection. Echinacea may also help reduce pain, which often occurs simultaneously with inflammation. Summary of the invention

[0018] The purpose of the present application is to provide a topical pharmaceutical preparation composition for improving the symptoms of skin diseases and its application in view of the deficiencies of the current technology. The topical pharmaceutical preparation composition for improving the symptoms of skin diseases of the present application, after using Echinacea extract in combination with clindamycin or any salt thereof, helps to eliminate bacterial inflammation, is very effective in treating acne, and has high safety.

[0019] In a first aspect, the present application provides a topical pharmaceutical preparation composition for improving symptoms of skin diseases, using the following technical solution: A local pharmaceutical preparation composition for improving symptoms of skin diseases comprises the following components: clindamycin phosphate, echinacea extract, a solvent, and a dermatologically acceptable carrier.

[0020] Preferably, the clindamycin phosphate and the Echinacea extract are present in any ratio.

[0021] Preferably, in terms of weight percentage, the concentration of the clindamycin phosphate is 0.5% w / w-1.5% w / w, and the concentration of the echinacea extract is 0.5% w / w-1.5% w / w.

[0022] Preferably, the solvent is at least one of an alcohol solvent and a non-alcohol solvent.

[0023] Preferably, the alcohol solvent is at least one of ethanol and isopropanol; and the non-alcohol solvent consists of diethylene glycol monoethyl ether and dimethyl sulfoxide.

[0024] Preferably, the dermatologically acceptable carrier is at least one of a gel, cream, ointment, lotion, foam, topical mixture, solution, emulsion, or a suitable topical dosage form.

[0025] Preferably, the pH value of the topical pharmaceutical preparation composition for improving symptoms of skin diseases is 5.3-5.7.

[0026] Preferably, the pH value of the topical pharmaceutical preparation composition for improving symptoms of skin diseases is 5.3-5.7 adjusted by sodium hydroxide or hydrochloric acid.

[0027] In a second aspect, the present application provides an application of a topical pharmaceutical preparation composition for improving symptoms of skin diseases, using the following technical solution: As a general technical concept, the present application also provides the above-mentioned topical pharmaceutical preparation composition for improving symptoms of skin diseases for treating acne and improving skin.

[0028] Several technical solutions of this application are described in detail as follows: The present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising: (i) a therapeutically effective amount of a combination of clindamycin or a pharmaceutically acceptable salt thereof and an echinacea extract; (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients.

[0029] The present application also discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, the composition comprising: (i) a therapeutically effective amount of a combination of clindamycin or a pharmaceutically acceptable salt thereof and an Echinacea extract; (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients, wherein the composition is substantially free of alcohol.

[0030] As used herein, a "therapeutically effective amount" of an active agent is an amount of a pharmaceutical agent or pharmacologically active agent sufficient to have a positive effect on the site of application. Thus, these amounts are sufficient to alter the skin disease, condition, or appearance being treated, but low enough to avoid serious side effects, within reasonable medical or dermatological recommendations. A therapeutically effective amount of a pharmaceutical pharmacologically active agent can provide significant relief when used repeatedly over a long period of time. The effective amount of a pharmacologically active agent will vary depending on the specific condition being treated, the severity of the condition, the duration of treatment, the specific ingredients of the composition being used, and other factors.

[0031] As used herein, "pharmaceutically acceptable salts" refer to non-toxic salts of the compounds of the present invention, which are generally prepared by reacting a free acid with a suitable organic or inorganic base, or by reacting a free base with a suitable acid.

[0032] The term "liquid preparation" refers to a pharmaceutical dosage form that is pourable and in a liquid state when used by a patient.

[0033] The term "composition" or "preparation composition", "pharmaceutical preparation composition" or "dosage form" or "external pharmaceutical preparation composition" or "external pharmaceutical composition" as used in this application synonymously includes dosage forms such as solutions, emulsions, creams, milks, gels, sprays, foams, lotions and shampoos. Here, it refers to solutions.

[0034] The term "Echinacea extract" refers to an extract obtained from the stem, leaf and root extracts of Echinacea purpurea, Echinacea angustifolia and Echinacea pallida, all of the Asteraceae family. In most cases, it is solid, liquid or semi-solid. The solid extract is a pale yellow-green powder, also known as Echinacea extract chicoric acid 1%-4%, polyphenols 4%, Echinacea extract, Echinacea herb PE, Echinacea polyphenols. The total phenol content of this product is ≥5.0% (UV), the chicoric acid content is ≥2.0% (HPLC), and the chicoric acid content is ≥4%. Echinacea is a perennial plant that usually grows in North America and Europe and is closely related to sunflowers, daisies and ragweed.

[0035] The term "pharmaceutically acceptable excipient" as used in this application means any material that can play a preventive and / or therapeutic role in the pharmaceutical composition, or the additive used may be inert. The purpose of adding such an additive is to make the pharmaceutical composition have acceptable technical characteristics and higher bioavailability.

[0036] The term "substantially alcohol-free" means that the alcohol content in the composition is less than about 10% (volume fraction), preferably less than about 5% (volume fraction), more preferably less than about 2.5% (volume fraction), more preferably less than about 1% (volume fraction), more preferably less than about 0.5% (volume fraction). In another embodiment, the composition is completely alcohol-free, i.e., no alcohol is added.

[0037] The present application also discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which composition comprises (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and an Echinacea extract; (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients, wherein the composition substantially contains one or more alcohols.

[0038] The term "essentially containing alcohol" means that the composition contains more than about 5% v / v, preferably more than about 10% v / v, more preferably more than about 20% v / v, more preferably more than about 40% v / v, more preferably more than about 50% v / v alcohol.

[0039] In one aspect, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of an Echinacea extract; wherein the clindamycin component is present in a concentration of about 0.05% to about 5% by weight per volume of the total composition, more preferably, in a concentration of about 0.1% to about 3% (by weight per volume of the total composition), more preferably, in a concentration of about 0.25% to about 2% by weight per volume of the total composition, more preferably, in a concentration of about 0.5% to about 1.5% by weight per volume of the total composition, more preferably, in a concentration of about 0.75% to about 1.25% by weight per volume of the total composition, more preferably, in a concentration of about 1% by weight per volume of the total composition. (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients.

[0040] On the other hand, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of an Echinacea extract; wherein the Echinacea extract component is present in a concentration of from about 0.001% to about 10% by weight per volume of the total composition, more preferably, in a concentration of from about 0.01% to about 7.5% (by weight of the total composition), more preferably, in a concentration of from about 0.1% to about 5% (by weight of the total composition), more preferably, in a concentration of from about 0.25% to about 2.5% (by weight of the total composition), more preferably, in a concentration of from about 0.5% to about 1.25% (by weight of the total composition), more preferably, in a concentration of about 1% (by weight of the total composition). (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients.

[0041] In another aspect, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier; wherein the carrier is any pharmaceutical preparation suitable for use on the skin, preferably a semisolid or liquid dosage form, more preferably a liquid, and most preferably a solution; (iii) one or more pharmaceutically acceptable excipients.

[0042] In another aspect, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising (i) a therapeutically effective amount of a combination of clindamycin or a pharmaceutically acceptable salt thereof and an echinacea extract; (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients, wherein the excipient is preferably selected from various types of gelling agents, emollients, antioxidants, chelating agents, moisturizing agents, emulsifiers, surfactants, pH regulators, solvents, cosolvents, wetting agents, stabilizers, viscosity regulators, buffers, preservatives and dispersants, more preferably gelling agents, chelating agents, moisturizing agents, surfactants, pH regulators, solvents, cosolvents, stabilizers, viscosity regulators, buffers and preservatives, and most preferably moisturizing agents, pH regulators, solvents, cosolvents and preservatives.

[0043] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which composition comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a Gel; (iii) one or more pharmaceutically acceptable excipients, wherein the excipients include polymers, alcohols, glycols, pH adjusters, stabilizers, preservatives and carriers.

[0044] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier as a Gel; (iii) one or more pharmaceutically acceptable excipients; wherein the polymer is selected from carbomer, a cellulose derivative, a natural polymer such as xanthan gum, guar gum or a combination thereof; wherein the alcohol is selected from ethanol, isopropanol or a combination thereof; wherein the glycol is selected from propylene glycol, butylene glycol, glycerol, hexylene glycol, propylene glycol or a combination thereof; wherein the pH adjuster is selected from sodium hydroxide, potassium hydroxide, ammonia, triethanolamine, hydrochloric acid, tetrabutylammonium hydroxide or a combination thereof; wherein the stabilizer is disodium ethylenediaminetetraacetic acid; wherein the preservative is selected from methylparaben or propylparaben, sodium benzoate, phenoxyethanol, benzyl alcohol, imidourea, sorbic acid or a combination thereof; or a combination of the two; wherein the carrier can be aqueous, such as purified water, or oily, such as any oil.

[0045] In a more preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a gel; (iii) one or more pharmaceutically acceptable excipients; wherein the polymer is selected from carbomer; wherein the alcohol is selected from isopropyl alcohol; the glycol is selected from propylene glycol; the pH adjuster is selected from sodium hydroxide and hydrochloric acid; the stabilizer is disodium ethylenediaminetetraacetic acid; the preservative is selected from methylparaben or propylparaben, or a combination of the two; and the carrier is selected from aqueous substances such as purified water.

[0046] In a more preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which includes (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a gel; and (iii) one or more pharmaceutically acceptable excipients, including carbomer, isopropyl alcohol propylene glycol, sodium hydroxide, disodium edetate, methyl benzoate and purified water.

[0047] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; and (iii) one or more pharmaceutically acceptable excipients, wherein the excipients comprise alcohols, glycols, pH adjusters and carriers.

[0048] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; (iii) one or more pharmaceutically acceptable excipients; wherein the alcohol is selected from ethanol, isopropanol or a combination of the two, the glycol is selected from propylene glycol, butylene glycol, glycerol, hexylene glycol, propanediol or a combination of the two, the pH adjuster is selected from sodium hydroxide, potassium hydroxide, ammonia water, triethanolamine, hydrochloric acid, tetrabutylammonium hydroxide or a combination of the two, and the carrier can be an aqueous solution such as purified water or any oil.

[0049] In a more preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; and (iii) one or more pharmaceutically acceptable excipients; wherein alcohols are selected from isopropanol; glycols are selected from propylene glycol; pH adjusters are selected from sodium hydroxide and hydrochloric acid; and the carrier is selected from an aqueous solution, such as purified water.

[0050] In a most preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which includes (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; and (iii) one or more pharmaceutically acceptable excipients, including isopropyl alcohol, propylene glycol, sodium hydroxide, hydrochloric acid and purified water.

[0051] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a Gel; (iii) one or more pharmaceutically acceptable excipients, wherein the excipients include polymers, novel solvents, glycols, pH regulators, stabilizers and carriers.

[0052] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier as a Gel; (iii) one or more pharmaceutically acceptable excipients; wherein the polymer is selected from carbomer, cellulose derivatives, natural polymers such as xanthan gum, guar gum or a combination thereof; wherein the novel solvent is selected from diethylene glycol monoethyl ether, dimethyl sulfoxide, n-methylene pyrrolidone, carbonate Any one or a combination of propylene glycol, hexylene glycol, caprylyl polyoxyethylene glycerol, dimethyl isosorbide; wherein the pH adjuster is selected from sodium hydroxide, potassium hydroxide, ammonia, triethanolamine, hydrochloric acid, tetrabutylammonium hydroxide or a combination thereof; wherein the stabilizer is disodium ethylenediaminetetraacetic acid; wherein the stabilizer is disodium ethylenediaminetetraacetic acid; wherein the preservative is selected from methyl parahydroxybenzoate or propyl parahydroxybenzoate, sodium benzoate, phenoxyethanol, benzyl alcohol, imidazole urea, sorbic acid or a mixture thereof; wherein the carrier can be aqueous, such as purified water, or oily, such as any oil.

[0053] In a more preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier as a Gel; (iii) one or more pharmaceutically acceptable excipients; wherein the polymer is selected from carbomer; wherein the new solvent is selected from diethylene glycol monoethyl ether, dimethyl sulfoxide or a combination of the two; wherein the glycol is selected from propylene glycol; wherein the pH regulator is selected from sodium hydroxide and hydrochloric acid; wherein the stabilizer is disodium ethylenediaminetetraacetic acid; wherein the preservative is selected from methyl parahydroxybenzoate or propyl parahydroxybenzoate or a combination of the two; wherein the carrier is selected from aqueous substances such as purified water.

[0054] In a more preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a gel; (iii) one or more pharmaceutically acceptable excipients, including carbomer, diethylene glycol monoethyl ether, propylene glycol, sodium hydroxide, disodium ethylenediaminetetraacetic acid, methylparaben and purified water.

[0055] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; and (iii) one or more pharmaceutically acceptable excipients, wherein the excipients include novel solvents, glycols, pH regulators and carriers.

[0056] In a preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier, as a solution; (iii) one or more pharmaceutically acceptable excipients; wherein the novel solvent is selected from any one of diethylene glycol monoethyl ether, dimethyl sulfoxide, n-methylene pyrrolidone, propylene carbonate, hexylene glycol, caprylyl polyoxyethylene glycerol, and dimethyl isosorbide or a combination thereof; wherein the ethylene glycol is selected from propylene glycol, butylene glycol, glycerol, hexylene glycol, propylene glycol or a combination thereof, the pH adjuster is selected from sodium hydroxide, potassium hydroxide, ammonia, triethanolamine, hydrochloric acid, tetrabutylammonium hydroxide or a combination thereof, and the carrier can be aqueous, such as purified water, or oily, such as any oil.

[0057] In a more preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, which comprises: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof and a combination of Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; (iii) one or more pharmaceutically acceptable excipients; wherein the novel solvent is selected from diethylene glycol monoethyl ether, dimethyl sulfoxide or a combination of the two; the glycol is selected from propylene glycol; the pH adjuster is selected from sodium hydroxide and hydrochloric acid; and the carrier is selected from an aqueous solution, such as purified water.

[0058] In a most preferred embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising: (i) a therapeutically effective amount of a combination of clindamycin or a pharmaceutically acceptable salt thereof and an Echinacea extract; (ii) a pharmaceutically acceptable carrier as a solution; and (iii) one or more pharmaceutically acceptable excipients, including diethylene glycol monoethyl ether, propylene glycol, sodium hydroxide, hydrochloric acid and purified water.

[0059] In a specific embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, comprising: (i) a therapeutically effective amount of clindamycin or a pharmaceutically acceptable salt thereof in combination with an Echinacea extract; (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients.

[0060] In another specific embodiment, the present application discloses a topical pharmaceutical preparation composition for improving symptoms of skin diseases, for improving skin conditions of skin inflammation and damage caused by acne, the composition comprising (i) a therapeutically effective amount of a combination of clindamycin or a pharmaceutically acceptable salt thereof and an Echinacea extract; (ii) a pharmaceutically acceptable carrier; and (iii) one or more pharmaceutically acceptable excipients.

[0061] In summary, the beneficial technical effects of this application are: 1. Synergistic effect: The combined use of clindamycin phosphate and echinacea extract can produce a synergistic effect and enhance the therapeutic effect on bacterial inflammation. This synergistic effect can more effectively eliminate the symptoms of skin diseases such as acne.

[0062] 2. Broad-spectrum antibacterial: Clindamycin is a broad-spectrum antibiotic that has inhibitory effects on a variety of bacteria. Echinacea extract also has multiple effects such as antibacterial, anti-inflammatory and immunomodulatory. The combination of the two can expand the scope of treatment and fight skin infections caused by different types of bacteria.

[0063] 3. Improved safety: Adding echinacea extract can improve the safety of topical drug preparations compared to using clindamycin phosphate alone. This may reduce the adverse reactions or side effects that patients may experience during use.

[0064] 4. Enhanced effectiveness: Due to the existence of synergistic effects, the composition may show higher efficacy in treating inflammatory lesions and non-inflammatory lesions. This means that it can deal with various types of skin problems more comprehensively.

[0065] 5. Good stability: The topical drug preparation composition has good stability, which means that it can maintain its efficacy over a certain period of time and is not easy to decompose or lose effectiveness. This is very important for long-term storage and use.

[0066] 6. Wide range of applications: Due to its broad-spectrum antibacterial and anti-inflammatory properties, the composition may be suitable for the treatment of a variety of skin diseases, including acne, eczema, dermatitis, etc.

[0067] 7. Improved patient compliance: Since the composition may have better efficacy and safety, patients may be more willing to follow the doctor's advice for treatment, thereby improving the success rate of treatment. DETAILED DESCRIPTION

[0068] The embodiments of the present application will be described in detail below in conjunction with the examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. In the examples, if specific conditions are not specified, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0069] Example 1 The material dosage is shown in Table 1; Table 1 Formula composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Echinacea Extract active 1.00%w / w 3 Isopropyl alcohol Solvents 50.00%v / v 4 Propylene glycol Moisturizer 8.00%v / v 5 hydrochloric acid pH Adjuster qsto pH 5.5 6 Purified water Carrier qsto 100 Steps: According to the formula ratio, clindamycin phosphate is dissolved in a mixture of isopropyl alcohol and propylene glycol under stirring, and the echinacea extract is added and mixed under stirring until a uniform mixture is formed, and purified water accounting for 90% of the total amount is added, and the pH value of the solution is adjusted to 5.5 with a 10% hydrochloric acid aqueous solution.

[0070] Example 2 The material usage is shown in Table 2; Table 2 Formulation Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Echinacea Extract active 1.00%w / w 3 Diethylene glycol monoethyl ether Solvents 10.00%v / v 4 Propylene glycol Moisturizer 10.00%v / v 5 Sodium hydroxide pH Adjuster qsto pH 5.52 6 Purified water Carrier qsto 100 Steps: According to the formula ratio, clindamycin phosphate is dissolved in a mixture of diethylene glycol monoethyl ether and propylene glycol under stirring, echinacea extract is added and mixed under stirring until a uniform mixture is formed, purified water accounting for 90% of the total amount is added, and the pH value of the solution is adjusted to 5.52 with a 10% sodium hydroxide aqueous solution.

[0071] Example 3 The material usage is shown in Table 3; Table 3 Formula composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 0.50%w / w 2 Echinacea Extract active 1.00%w / w 3 Isopropyl alcohol Solvents 50.00%v / v 4 Propylene glycol Moisturizer 8.00%v / v 5 Sodium hydroxide pH Adjuster qsto pH 5.5 6 Purified water Carrier qsto 100 Steps: Dissolve clindamycin phosphate in a mixture of isopropyl alcohol and propylene glycol under stirring according to the formula ratio, add and mix the echinacea extract under stirring until a uniform mixture is formed, add purified water accounting for 90% of the total amount, and adjust the pH value of the solution to 5.7 with a 10% sodium hydroxide aqueous solution.

[0072] Example 4 The material usage is shown in Table 4; Table 4 Formula composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Echinacea Extract active 0.50%w / w 3 Isopropyl alcohol Solvents 50.00%v / v 4 Propylene glycol Moisturizer 8.00%v / v 5 hydrochloric acid pH Adjuster qsto pH 5.4 6 Purified water Carrier qsto 100 Steps: Dissolve clindamycin phosphate in a mixture of isopropyl alcohol and propylene glycol under stirring according to the formula ratio, add and mix the echinacea extract under stirring until a uniform mixture is formed, add purified water accounting for 90% of the total amount, and adjust the pH value of the solution to 5.3 with a 10% hydrochloric acid aqueous solution.

[0073] Example 5 The material usage is shown in Table 5; Table 5 Formula composition Steps: Dissolve clindamycin phosphate in a mixture of ethanol and propylene glycol under stirring according to the formula ratio, add and mix the echinacea extract under stirring until a uniform mixture is formed, add 90% of the total amount of purified water, and adjust the pH value of the solution to 5.4 with a 10% hydrochloric acid aqueous solution.

[0074] Example 6 The material usage is shown in Table 6; Table 6 Formula composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Echinacea Extract active 1.00%w / w 3 Isopropyl alcohol Solvents 50.00%w / w 4 Propylene glycol Moisturizer 8.00%w / w 5 Sodium hydroxide pH Adjuster qsto pH 5.46 6 Methylparaben preservative 0.20%w / w 7 Carbomer Homopolymer Gelling Agent 1.00%w / w 8 Disodium EDTA Chelating agents 0.10%w / w 9 Purified water Carrier qsto 100%w / w Steps: according to the formula ratio, under stirring, methyl paraben and disodium ethylenediaminetetraacetate are added and dissolved in propylene glycol, heated and cooled at room temperature to dissolve. Carbomer homopolymer is added under stirring, and stirring is continued until a uniform dispersion is formed to obtain a polymer dispersion; under stirring, clindamycin phosphate is added to isopropanol and dissolved until a transparent solution is formed, and echinacea extract is added and mixed under stirring until a uniform mixture is formed to obtain a drug mixture; the drug mixture is added to the polymer dispersion, and 90% of the total amount of purified water is added under stirring, and stirring is continued for 60 minutes, and the pH value of the solution is adjusted to 5.46 with 10% sodium hydroxide aqueous solution, and the volume is increased to 100% with the remaining purified water.

[0075] Example 7 The material usage is shown in Table 7; Table 7 Recipe composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Echinacea Extract active 1.00%w / w 3 Ethanol Solvents 50.00%w / w 4 Propylene glycol Moisturizer 8.00%w / w 5 Sodium hydroxide pH Adjuster qsto pH 5.7 6 Methylparaben preservative 0.20%w / w 7 Carbomer Homopolymer Gelling Agent 1.00%w / w 8 Disodium EDTA Chelating agents 0.10%w / w 9 Purified water Carrier qsto 100%w / w Steps: according to the formula ratio, under stirring, methyl paraben and disodium ethylenediaminetetraacetate are added and dissolved in propylene glycol, heated and cooled at room temperature to dissolve. Carbomer homopolymer is added under stirring, and stirring is continued until a uniform dispersion is formed to obtain a polymer dispersion; under stirring, clindamycin phosphate is added to ethanol and dissolved until a transparent solution is formed, and echinacea extract is added and mixed under stirring until a uniform mixture is formed to obtain a drug mixture; the drug mixture is added to the polymer dispersion, and 90% of the total amount of purified water is added under stirring, and stirring is continued for 60 minutes, and the pH value of the solution is adjusted to 5.7 with 10% sodium hydroxide aqueous solution, and the volume is increased to 100% with the remaining purified water.

[0076] Example 8 The material usage is shown in Table 8; Table 8 Recipe composition Steps: according to the formula ratio, under stirring, methyl paraben and disodium ethylenediaminetetraacetate are added and dissolved in propylene glycol. If necessary, heat and cool at room temperature to dissolve. Carbomer homopolymer is added under stirring, and stirring is continued until a uniform dispersion is formed to obtain a polymer dispersion; clindamycin phosphate in diethylene glycol monoethyl ether is added under stirring until a uniform mixture is formed, and echinacea extract is added and mixed under stirring until a uniform mixture is formed to obtain a drug mixture; the drug mixture is added to the polymer dispersion, and 90% of the total amount of purified water is added under stirring, and stirring is continued for 60 minutes, and the pH value of the solution is adjusted to 5.5 with 10% sodium hydroxide aqueous solution, and the volume is increased to 100% with the remaining purified water.

[0077] Example 9 The material usage is shown in Table 9; Table 9 Formula composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Echinacea Extract active 2.00%w / w 3 Dimethyl sulfoxide Solvents 5.00%w / w 4 Propylene glycol Moisturizer 8.00%w / w 5 Sodium hydroxide pH Adjuster qsto pH 5.6 6 Methylparaben preservative 0.20%w / w 7 Carbomer Homopolymer Gelling Agent 1.00%w / w 8 Disodium EDTA Chelating agents 0.10%w / w 9 Purified water Carrier qsto 100%w / w Steps: according to the formula ratio, under stirring, methyl paraben and disodium ethylenediaminetetraacetate are added and dissolved in propylene glycol, heated and cooled at room temperature to dissolve, carbomer homopolymer is added under stirring, and stirring is continued until a uniform dispersion is formed to obtain a polymer dispersion; clindamycin phosphate in dimethyl sulfoxide is added under stirring until a uniform mixture is formed. Echinacea extract is added and mixed under stirring until a uniform mixture is formed to obtain a drug mixture; the drug mixture is added to the polymer dispersion, 90% of the total amount of purified water is added under stirring, stirring is continued for 60 minutes, the pH value of the solution is adjusted to 5.6 with 10% sodium hydroxide aqueous solution, and the volume is increased to 100% with the remaining purified water.

[0078] Comparative Example 1 The material usage is shown in Table 10; Table 10 Formulation Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Isopropyl alcohol Solvents 50.00%v / v 3 Propylene glycol Moisturizer 8.00%v / v 4 Sodium hydroxide pH Adjuster qsto pH 5.5 5 Purified water Carrier qsto 100 Steps: According to the formula ratio, dissolve clindamycin phosphate in a mixture of isopropanol and propylene glycol under stirring, add 90% of the total amount of purified water, adjust the pH value of the solution to 5.5 with 10% sodium hydroxide aqueous solution, and use the remaining purified water to make the capacity reach 100%.

[0079] Comparative Example 2 The material usage is shown in Table 11; Table 11 Formula composition Serial number Ingredient name Effect of ingredients concentration 1 Clindamycin phosphate active 1.00%w / w 2 Isopropyl alcohol Solvents 50.00%w / w 3 Propylene glycol Moisturizer 8.00%w / w 4 Sodium hydroxide pH Adjuster qsto pH 5.55 5 Methylparaben preservative 0.20%w / w 6 Carbomer Homopolymer Gelling Agent 1.00%w / w 7 Disodium EDTA Chelating agents 0.10%w / w 8 Purified water Carrier qsto 100%w / w Steps: according to the formula ratio, under stirring, add and dissolve methyl paraben and disodium ethylenediaminetetraacetate in propylene glycol, heat and cool at room temperature to dissolve, add carbomer homopolymer under stirring, continue stirring until a uniform dispersion is formed, and obtain a polymer dispersion; under stirring, add clindamycin phosphate to isopropanol and dissolve until a transparent solution is formed to obtain a drug mixture; add the drug solution to the polymer dispersion, add 90% of the total amount of purified water under stirring, continue stirring for 60 minutes, adjust the pH value of the solution to 5.55 with 10% sodium hydroxide aqueous solution, and increase the volume to 100% with the remaining purified water.

[0080] Test Example 1: Stability The stability test of the topical pharmaceutical preparation composition for improving the symptoms of skin diseases was conducted under accelerated storage conditions, where the accelerated storage conditions (ACC) were 40C / 75% relative humidity for 3 months (M). The samples of the topical pharmaceutical preparation composition solution for improving the symptoms of skin diseases prepared in Examples 1, 2, 6 and Comparative Example 2 were subjected to initial analysis (0M) and pH value, assay and impurity analysis after accelerated storage for 3 months. The test results are shown in Table 12.

[0081] Table 12 Stability results From the data in Table 12, it can be seen that the topical pharmaceutical preparation composition for improving the symptoms of skin diseases prepared in the present application has good stability in terms of pH value, assay and organic impurities.

[0082] Test Case 2 Safety and Efficacy Study The subjects of the efficacy study were 68 patients, who were divided into two groups, 34 in each group. The samples of Comparative Example 1 and Example 1 were provided to patients in Group 1 and Group 2, respectively. Patients were asked to use the solution after cleaning their faces with the ordinary cleanser provided. In addition, they were asked not to wash their faces for at least two hours after using the drug. All subjects were evaluated for the counts of total lesions, inflammatory baseline lesions, and non-inflammatory baseline lesions at the beginning of treatment and at the end of 12 weeks of treatment. The safety test is shown in Table 13; the efficacy results of total lesions, inflammatory baseline lesions, and non-inflammatory baseline lesions are shown in Table 14.

[0083] Table 13 Safety The safety information in Table 13 shows that the safety of the topical pharmaceutical preparation composition for improving the symptoms of skin diseases prepared in Example 1 is improved, and the effects of burning, itching and dryness are reduced.

[0084] Table 14 Efficacy results for total lesions, inflammatory baseline lesions, and non-inflammatory baseline lesions The data in Table 14 show that compared with the clindamycin phosphate solution, the topical pharmaceutical preparation composition for improving the symptoms of skin diseases prepared in Example 1 of the present application, using the combination of clindamycin phosphate and Echinacea extract, can produce a synergistic effect, and the obtained composition has better safety and effectiveness.

[0085] The above embodiments are only used to explain the technical solutions of the present application rather than to limit them. Although the above embodiments provide a specific description of the present application, relevant technical personnel should understand that the specific implementation methods of the present application can still be modified or replaced by equivalents, and any modifications and equivalent replacements that do not depart from the spirit and scope of the present application should be included in the scope of protection of the present application.

Claims

1. A topical pharmaceutical preparation composition for improving the symptoms of skin diseases, characterized in that: The invention comprises the following components: clindamycin phosphate, echinacea extract, solvent and dermatologically acceptable carrier.

2. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to claim 1, characterized in that: The clindamycin phosphate and the echinacea extract are present in any ratio.

3. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to claim 1, characterized in that: In terms of weight percentage, the concentration of the clindamycin phosphate is 0.5% w / w-1.5% w / w, and the concentration of the echinacea extract is 0.5% w / w-1.5% w / w.

4. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to claim 1, characterized in that: The solvent is at least one of an alcohol solvent and a non-alcohol solvent.

5. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to claim 4, characterized in that: The alcohol solvent is at least one of ethanol and isopropanol; the non-alcohol solvent consists of diethylene glycol monoethyl ether and dimethyl sulfoxide.

6. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to claim 1, characterized in that: The dermatologically acceptable carrier is at least one of a gel, cream, ointment, lotion, foam, topical mixture, solution, emulsion, or a suitable topical dosage form.

7. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to any one of claim 1, characterized in that: The pH value of the topical pharmaceutical preparation composition for improving the symptoms of skin diseases is 5.3-5.

7.

8. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to any one of claim 1, characterized in that: The pH value of the topical pharmaceutical preparation composition for improving symptoms of skin diseases is 5.3-5.7 and is adjusted with sodium hydroxide or hydrochloric acid.

9. A topical pharmaceutical preparation composition for improving symptoms of skin diseases according to any one of claims 1 to 8, which is used for treating acne and improving skin.

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