CN114452297A - Medicinal preparation for treating dermatitis and preparation method thereof - Google Patents
Medicinal preparation for treating dermatitis and preparation method thereof Download PDFInfo
- Publication number
- CN114452297A CN114452297A CN202111681747.4A CN202111681747A CN114452297A CN 114452297 A CN114452297 A CN 114452297A CN 202111681747 A CN202111681747 A CN 202111681747A CN 114452297 A CN114452297 A CN 114452297A
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- parts
- glucocorticoid
- preparation
- pharmaceutical composition
- dermatitis
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- 201000004624 Dermatitis Diseases 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 71
- 239000003862 glucocorticoid Substances 0.000 claims abstract description 44
- 150000004676 glycans Chemical class 0.000 claims abstract description 41
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 41
- 239000005017 polysaccharide Substances 0.000 claims abstract description 41
- DVGGLGXQSFURLP-FIZCXTQCSA-N potengriffioside A Natural products O[C@@H]1[C@@H](COC(=O)C=Cc2ccc(O)cc2)O[C@@H](Oc2c(oc3cc(O)cc(O)c3c2=O)-c2ccc(O)cc2)[C@H](O)[C@H]1O DVGGLGXQSFURLP-FIZCXTQCSA-N 0.000 claims abstract description 40
- LTRRTGCXRIMDTF-UHFFFAOYSA-N tiliroside Natural products OC1C(COC(=O)C=Cc2ccc(O)cc2)OC(OC3=C(Oc4cc(O)cc(O)c4C3)c5ccc(O)c(O)c5)C(O)C1O LTRRTGCXRIMDTF-UHFFFAOYSA-N 0.000 claims abstract description 40
- DVGGLGXQSFURLP-VWMSDXGPSA-N tribuloside Chemical compound C([C@@H]1[C@H]([C@@H]([C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1)O)O)OC(=O)\C=C\C1=CC=C(O)C=C1 DVGGLGXQSFURLP-VWMSDXGPSA-N 0.000 claims abstract description 40
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 claims abstract description 32
- 229960001347 fluocinolone acetonide Drugs 0.000 claims abstract description 25
- 241001313855 Bletilla Species 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 66
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 60
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- 239000006071 cream Substances 0.000 claims description 28
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 26
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 21
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 21
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 21
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 21
- 238000002156 mixing Methods 0.000 claims description 21
- 239000012071 phase Substances 0.000 claims description 21
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- 229940057995 liquid paraffin Drugs 0.000 claims description 20
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 20
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 20
- 239000008117 stearic acid Substances 0.000 claims description 20
- 239000003871 white petrolatum Substances 0.000 claims description 20
- 238000010438 heat treatment Methods 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 14
- JVKUCNQGESRUCL-UHFFFAOYSA-N 2-Hydroxyethyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCCO JVKUCNQGESRUCL-UHFFFAOYSA-N 0.000 claims description 10
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- 239000008346 aqueous phase Substances 0.000 claims description 7
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- 108090000695 Cytokines Proteins 0.000 abstract description 3
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- 241001313857 Bletilla striata Species 0.000 description 21
- 230000000052 comparative effect Effects 0.000 description 18
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 16
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- 241000699666 Mus <mouse, genus> Species 0.000 description 13
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- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
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- 229960001660 histamine phosphate Drugs 0.000 description 4
- ZHIBQGJKHVBLJJ-UHFFFAOYSA-N histamine phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.NCCC1=CNC=N1 ZHIBQGJKHVBLJJ-UHFFFAOYSA-N 0.000 description 4
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- 206010012434 Dermatitis allergic Diseases 0.000 description 3
- 201000009053 Neurodermatitis Diseases 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
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- 208000008742 seborrheic dermatitis Diseases 0.000 description 3
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- 238000011069 regeneration method Methods 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 206010040882 skin lesion Diseases 0.000 description 2
- 231100000444 skin lesion Toxicity 0.000 description 2
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- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- NLZCOTZRUWYPTP-MIUGBVLSSA-N 5-hydroxy-2-(4-methoxyphenyl)-7-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one Chemical compound C1=CC(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 NLZCOTZRUWYPTP-MIUGBVLSSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 description 1
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
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- NLZCOTZRUWYPTP-UHFFFAOYSA-N acacetin-7-O-beta-D-galactoside Natural products C1=CC(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2OC1C(O)C(O)C(O)C(CO)O1 NLZCOTZRUWYPTP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a medicinal preparation for treating dermatitis and a preparation method thereof. The medicinal preparation for treating dermatitis is prepared from a medicinal composition and pharmaceutically acceptable auxiliary materials; the pharmaceutical composition consists of tiliroside, bletilla polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla polysaccharide to glucocorticoid is (5-15) to (3-12): 1; the glucocorticoid is fluocinolone acetonide or fluocinolone acetonide. The tiliroside, the bletilla polysaccharide and the glucocorticoid are compounded for treating dermatitis for the first time, so that the tiliroside, the bletilla polysaccharide and the glucocorticoid have the effects of resisting inflammation, resisting allergy and relieving itching of the glucocorticoid, can inhibit inflammatory signal paths, interfere signal transduction of proinflammatory cytokines, prevent skin wound infection, repair damaged skin, protect skin barriers, reduce the occurrence of hormone-dependent dermatitis caused by improper hormone external use, and improve the treatment effect.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a medicinal preparation for treating dermatitis and a preparation method thereof.
Background
The chemical name of fluocinolone acetonide is 11 beta, 21-dihydroxy-16 alpha, 17- [ (1-methylethylidene) -bis (oxy) ] -6 alpha, 9-difluoropregna-1, 4-diene-3, 20-dione, and the CAS No. of fluocinolone acetonide is 67-73-2; the fluocinonide has the chemical name of 11 beta-hydroxy-16 alpha, 17- [ (1-methylethylidene) -bis (oxy) ] -21- (acetoxyl) -6 alpha, 9-difluoropregna-1, 4-diene-3, 20-dione, the CAS No. of the fluocinonide is 356-12-7, and the fluocinonide is 21-position acetate of fluocinonide, which belong to corticoids, can be externally used for contracting dermal capillaries, inhibiting proliferation or regeneration of epidermal cells, inhibiting regeneration of fibroblasts in connective tissues, stabilizing intracellular lysosome membranes, preventing tissue damage caused by release of lysosomal enzymes, and has strong anti-inflammatory and anti-allergic effects. Can be used for treating dermatoses such as allergic dermatitis, atopic dermatitis, contact dermatitis, seborrheic dermatitis, eczema, skin pruritus, psoriasis, and neurodermatitis.
However, long-term use of fluocinolone acetonide or fluocinolone acetonide results in a series of skin barrier disruption problems, manifested by skin atrophy, telangiectasia, purpura, vellus hirsutus increase and acneiform skin lesions, with varying degrees of itching, burning and other symptoms, and also hormone-dependent dermatitis. The hormone-dependent dermatitis is a subacute inflammatory dermatosis which is caused by that the original skin lesion and symptoms are remarkably improved after the preparation containing the glucocorticoid (such as fluocinolone acetonide, fluocinolone acetonide and the like) is externally applied, and the original symptoms and physical signs relapse or even aggravation can be caused once the preparation is stopped, so that the patient is forced to be externally applied with the glucocorticoid again. Studies have shown that hormone-dependent dermatitis is associated with long-term overdose, over-concentration, and over-range topical glucocorticoid formulations. Aiming at the problems of skin barrier damage and hormone-dependent dermatitis caused by long-term use of the conventional external medicinal preparation containing fluocinolone acetonide or fluocinolone acetonide, the pharmaceutical preparation which can treat inflammatory diseases of the skin and repair the skin is urgently needed to be provided.
Disclosure of Invention
Aiming at the problems and the defects in the prior art, the invention aims at providing a medicinal preparation for treating dermatitis and a preparation method thereof.
In order to realize the purpose of the invention, the technical scheme adopted by the invention is as follows:
the invention provides a pharmaceutical composition, which consists of tiliroside, bletilla polysaccharide and glucocorticoid, wherein the weight ratio of the tiliroside to the bletilla polysaccharide to the glucocorticoid is (5-15) to (3-12): 1.
according to the pharmaceutical composition, preferably, the weight ratio of tiliroside, bletilla striata polysaccharide and glucocorticoid is 10:8: 1.
preferably, the glucocorticoid is fluocinolone acetonide or fluocinolone acetonide according to the pharmaceutical composition described above. More preferably, the glucocorticoid is fluocinolone acetonide.
In a second aspect, the present invention provides a use of the pharmaceutical composition of the first aspect in the preparation of a medicament for treating dermatitis.
According to the above use, preferably, the dermatitis comprises contact dermatitis, allergic dermatitis, atopic dermatitis, seborrheic dermatitis, neurodermatitis, atopic dermatitis, skin pruritus and psoriasis.
The third aspect of the invention provides a pharmaceutical preparation for treating dermatitis, which is prepared from the pharmaceutical composition of the first aspect and pharmaceutically acceptable auxiliary materials.
Preferably, the pharmaceutical preparation for treating dermatitis is a cream, a solution, a gel, a liniment or a lotion.
According to the above dermatitis treatment pharmaceutical preparation, preferably, the pharmaceutical preparation is a cream, and the pharmaceutical preparation comprises the following components in parts by weight: 0.01-1 part of pharmaceutical composition, 0.5-1.6 parts of Transcutol P, 150.8-2.6 parts of Solutol HS, 6-12 parts of stearic acid, 6-15 parts of white vaseline, 5-12 parts of liquid paraffin, 2-12 parts of glycerol, 0.01-0.6 part of ethylparaben and 46-65 parts of water.
According to the above pharmaceutical preparation for treating dermatitis, preferably, the pharmaceutical preparation comprises the following components in parts by weight: 0.24 part of pharmaceutical composition, 1 part of Transcutol P, 152 parts of Solutol HS, 7 parts of stearic acid, 10 parts of white vaseline, 8 parts of liquid paraffin, 8 parts of glycerol, 0.16 part of ethylparaben and 63.6 parts of water.
According to the above pharmaceutical preparation for treating dermatitis, preferably, the dermatitis comprises contact dermatitis, allergic dermatitis, atopic dermatitis, seborrheic dermatitis, neurodermatitis, atopic dermatitis, skin pruritus, and psoriasis.
In a fourth aspect, the present invention provides a method for preparing the pharmaceutical preparation for treating dermatitis according to the third aspect. The preparation method comprises the following steps:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 60-70 ℃ to obtain an aqueous phase solution;
(2) dissolving the medicinal composition in Transcutol P to obtain a medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 65-75 deg.C to obtain oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation for treating dermatitis.
In the pharmaceutical composition of the invention, the effects and actions of the components are as follows:
tiliroside: tiliroside is also called kaempferol-3-O-beta-D- (6' -O-trans-p-hydroxy cinnamoyl) glucopyranoside, tiliroside, tribulus terrestris glycoside, buddlein glycoside, etc., is a flavonoid glycoside compound, and is yellow needle crystal. Tiliroside has strong antioxidant activity, free radical scavenging activity, antibacterial and anti-inflammatory activity, can scavenge free radicals, has antioxidant effect and anti-allergic reaction, and has inhibitory effect on mouse contact dermatitis caused by 2, 4-dinitrochlorobenzene.
And (3) rhizoma bletillae polysaccharide: the bletilla polysaccharide is an extract of bletilla (also called bletilla striata), has antibacterial, antiviral and anti-inflammatory effects, can protect mucous membrane and promote wound healing, and researches show that the mechanism of the bletilla polysaccharide for promoting wound healing is possibly related to the inhibition of a TLR4/LPS signal channel and the expression of downstream inflammatory factors TNF-alpha and IL-6, and interferes with proinflammatory cytokine signal transduction through the inhibition of an inflammation signal channel, so that the effects of preventing wound infection and promoting wound healing are achieved; meanwhile, the bletilla polysaccharide also has the effects of resisting oxidation, delaying skin aging, moisturizing, removing freckles, whitening, resisting wrinkles, preventing sunburn and the like.
Compared with the prior art, the invention has the following positive beneficial effects:
(1) the tiliroside, the bletilla polysaccharide and the glucocorticoid are compounded for treating dermatitis for the first time, so that the tiliroside, the bletilla polysaccharide and the glucocorticoid have the effects of resisting inflammation, resisting allergy and relieving itching of the glucocorticoid, can inhibit inflammatory signal paths, interfere signal transduction of proinflammatory cytokines, prevent skin wound infection, repair damaged skin, protect skin barriers, reduce the occurrence of hormone-dependent dermatitis caused by improper hormone external use, and improve the treatment effect.
(2) The tiliroside and the bletilla polysaccharide in the pharmaceutical composition have antibacterial and anti-inflammatory activities, and the dosage of glucocorticoid in the pharmaceutical preparation can be reduced on the basis of achieving the same treatment effect by compounding the tiliroside, the bletilla polysaccharide and the glucocorticoid, and the prepared pharmaceutical preparation has good spreadability on skin and good moisturizing performance.
(3) Fluocinonide is difficult to dissolve, dimethyl sulfoxide is usually adopted as a solvent for dissolving, but dimethyl sulfoxide is toxic, and the dimethyl sulfoxide can enter the skin after contacting the skin, so that the harm is caused to the human body; moreover, when the dimethyl sulfoxide contacts the skin, the dimethyl sulfoxide easily burns the skin and causes the skin to feel stabbing pain, and is not beneficial to the treatment of skin inflammation and the recovery of wound surfaces. When the medicinal preparation for treating dermatitis is prepared, the Transcutol P is adopted to dissolve fluocinonide, tiliroside and bletilla polysaccharide, the fluocinonide can be well dissolved in the Transcutol P, and the Transcutol P has low toxicity, no stimulation to skin and safe use. In addition, the invention adopts Solutol HS15 as an emulsifying dispersant, Transcutol P and Solutol HS15 can be mutually soluble, and through the interaction of Transcutol P and Solutol HS15, the dispersion of fluocinonide, tiliroside and bletilla polysaccharide in the cream pharmaceutical preparation can be well realized, and the cream pharmaceutical preparation has no stimulation to skin and can improve the transdermal effect of the drugs.
Detailed Description
The present invention will be described in further detail with reference to specific examples. Materials and chemical reagents used in the examples are all conventional commercial products unless otherwise specified, and the technical means used are conventional means known to those skilled in the art.
Example 1:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 10:8: 1. The glucocorticoid is fluocinonide.
Example 2:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 15:3: 1. The glucocorticoid is fluocinonide.
Example 3:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 5:12: 1. The glucocorticoid is fluocinonide.
Example 4:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 8:10: 1. The glucocorticoid is fluocinonide.
Example 5:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 6:9: 1. The glucocorticoid is fluocinonide.
Example 6:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 12:5: 1. The glucocorticoid is fluocinolone acetonide.
Example 7:
a pharmaceutical composition comprises tiliroside, bletilla striata polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla striata polysaccharide to glucocorticoid in the pharmaceutical composition is 10:12: 1. The glucocorticoid is fluocinonide.
Example 8:
the pharmaceutical preparation for treating dermatitis is cream, and comprises the following components in parts by weight: 0.24g of pharmaceutical composition, 1g of Transcutol P, 7g of Solutol HS 152 g, stearic acid, 10g of white vaseline, 8g of liquid paraffin, 8g of glycerol, 0.16g of ethylparaben and 63.6g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the medicinal preparation for treating dermatitis comprises the following specific steps:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 65 ℃ to obtain an aqueous phase solution;
(2) dissolving the medicinal composition in Transcutol P to obtain a medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 70 deg.C to obtain oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation for treating dermatitis.
Example 9:
the pharmaceutical preparation for treating dermatitis is cream, and comprises the following components in parts by weight: 0.5g of pharmaceutical composition, 0.8g of Transcutol P, 0.2g of Solutol HS152.2g, 6g of stearic acid, 12g of white vaseline, 10g of liquid paraffin, 10g of glycerol, 0.5g of ethylparaben and 58g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the medicinal preparation for treating dermatitis comprises the following specific steps:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 60 ℃ to obtain an aqueous phase solution;
(2) dissolving the medicinal composition in Transcutol P to obtain a medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 75 deg.C to obtain oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation for treating dermatitis.
Example 10:
the pharmaceutical preparation for treating dermatitis is cream, and comprises the following components in parts by weight: 0.01g of pharmaceutical composition, 0.5g of Transcutol P, 152.6 g of Solutol HSS, 8g of stearic acid, 12g of white vaseline, 10g of liquid paraffin, 12g of glycerol, 0.09g of ethylparaben and 54.8g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the medicinal preparation for treating dermatitis comprises the following specific steps:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 70 ℃ to obtain an aqueous phase solution;
(2) dissolving the medicinal composition in Transcutol P to obtain a medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 65 ℃ to obtain an oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation for treating dermatitis.
Example 11:
the pharmaceutical preparation for treating dermatitis is a cream, and comprises the following components in parts by weight: 0.1g of pharmaceutical composition, 0.6g of Transcutol P, 0.4 g of Solutol HS151.4g, 6g of stearic acid, 15g of white vaseline, 12g of liquid paraffin, 12g of glycerol, 0.1g of ethylparaben and 52.8g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the pharmaceutical preparation for treating dermatitis is the same as that of example 8.
Example 12:
the pharmaceutical preparation for treating dermatitis is cream, and comprises the following components in parts by weight: 0.8g of pharmaceutical composition, 1.2g of Transcutol P, 152.0 g of Solutol HSS, 12g of stearic acid, 12g of white vaseline, 5g of liquid paraffin, 2g of glycerol, 0.5g of ethylparaben and 64.5g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the pharmaceutical preparation for treating dermatitis is the same as that of example 8.
Example 13:
the pharmaceutical preparation for treating dermatitis is cream, and comprises the following components in parts by weight: 1g of pharmaceutical composition, 1.6g of Transcutol P, 150.8 g of Solutol HSS, 8g of stearic acid, 10g of white vaseline, 8g of liquid paraffin, 12g of glycerol, 0.6g of ethylparaben and 58g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the pharmaceutical preparation for treating dermatitis is the same as that of example 8.
Example 14:
the pharmaceutical preparation for treating dermatitis is cream, and comprises the following components in parts by weight: 0.3g of pharmaceutical composition, 1.2g of Transcutol P, Solutol HS 152 g, 12g of stearic acid, 15g of white vaseline, 12g of liquid paraffin, 12g of glycerol, 0.5g of ethylparaben and 46g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The preparation method of the pharmaceutical preparation for treating dermatitis is the same as that of example 8.
Example 15:
example 15 is substantially the same as example 8 except that: the pharmaceutical composition adopted in the pharmaceutical preparation for treating dermatitis is the pharmaceutical composition described in example 2.
Example 16:
the contents of example 16 are substantially the same as those of example 9, except that: the pharmaceutical composition adopted in the pharmaceutical preparation for treating dermatitis is the pharmaceutical composition described in example 3.
Example 17:
example 17 is substantially the same as example 8 except that: the pharmaceutical composition adopted in the pharmaceutical preparation for treating dermatitis is the pharmaceutical composition described in example 4.
Example 18:
the contents of example 18 are substantially the same as those of example 8, except that: the pharmaceutical composition adopted in the pharmaceutical preparation for treating dermatitis is the pharmaceutical composition described in example 5.
Example 19:
example 19 is substantially the same as example 8 except that: the pharmaceutical composition adopted in the pharmaceutical preparation for treating dermatitis is the pharmaceutical composition described in example 6.
Example 20:
example 20 is substantially the same as example 9 except that: the pharmaceutical composition adopted in the pharmaceutical preparation for treating dermatitis is the pharmaceutical composition described in example 7.
Example 21:
the pharmaceutical preparation for treating dermatitis is a solution, and comprises the following components in parts by weight: 1g of medicine composition, 1.0g of Transcutol P, 152.0 g of Solutol HS152, 0.2g of ethylparaben and 96.8g of water. Wherein the pharmaceutical composition is the pharmaceutical composition of example 1.
The efficacy verification experiment of the medicinal preparation for treating dermatitis comprises the following steps:
an efficacy verification experiment was performed using the pharmaceutical preparation for treating dermatitis prepared in example 8 of the present invention as an example. Meanwhile, in order to compare with the pharmaceutical preparation for treating dermatitis of the present invention, the present invention also carried out comparative tests, the details of which are shown in comparative examples 1 to 3.
Comparative example 1:
a pharmaceutical preparation is a cream, and comprises the following components in parts by weight: tiliroside 0.126g, Transcutol P1 g, Solutol HS 152 g, stearic acid 7g, white vaseline 10g, liquid paraffin 8g, glycerol 8g, ethylparaben 0.16g, and water 63.714 g.
The preparation method of the medicinal preparation comprises the following specific steps:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 65 ℃ to obtain an aqueous phase solution;
(2) dissolving tilianin in Transcutol P to obtain medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 70 deg.C to obtain oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation.
Comparative example 2:
a pharmaceutical preparation is a cream, and comprises the following components in parts by weight: 0.1g of bletilla polysaccharide, 1g of Transcutol P, 152 g g of Solutol HS, 7g of stearic acid, 10g of white vaseline, 8g of liquid paraffin, 8g of glycerol, 0.16g of ethylparaben and 63.74g of water.
The preparation method of the medicinal preparation comprises the following specific steps:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 65 ℃ to obtain an aqueous phase solution;
(2) dissolving rhizoma bletilla polysaccharide in Transcutol P to obtain medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 70 ℃ to obtain an oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation.
Comparative example 3:
comparative example 3 is substantially the same as example 8 except that the formulation does not contain a pharmaceutical composition.
1. Experiment for inhibiting mouse auricle swelling caused by paraxylene by using medicinal preparation for treating dermatitis
(1) Experimental drugs: the pharmaceutical preparation for treating dermatitis prepared in example 8 of the present invention, the pharmaceutical preparations prepared in comparative experiments 1 to 3, and the fluocinolone acetonide cream commercially available (the specification is 10g, and the amount of fluocinolone acetate in 10g of fluocinolone acetate cream is 2.5 mg).
(2) Test animals: SPF grade ICR mice were 48, male, and weighed 18-22 g.
(3) The test method comprises the following steps: the 48 mice were randomly divided into a blank control group, an experimental group, a control group 1, a control group 2, a control group 3 and a positive control group, 8 mice per group. The right ear of each group of mice was smeared with the corresponding drug according to the group of mice in Table 1, 0.1g each time, and the drug was applied in the morning and evening in turn each day for 4 days. Coating 30 mu l of dimethylbenzene on the front and back surfaces of the right auricle of the mouse 40min after the last coating, dislocating the cervical vertebra after 1h to kill the mouse, taking down the round lug plate from the consenting part of the left and right auricles of the mouse by a puncher (with the diameter of 7mm) and weighing, calculating the inhibition rate of different medicinal preparations on auricle swelling by taking the weight difference of the left and right lug plates as an index of the swelling degree, and performing significance determination and comparison with a model group by adopting an inter-group t test method. Specific results are shown in table 1. Wherein, swelling degree is right ear weight-left ear weight; inhibition rate ═ 100% of (swelling degree of blank control group-swelling degree of administration group)/blank control group.
TABLE 1 Effect of each pharmaceutical preparation on swelling of mouse auricle caused by Paralyne
| Group of | Smearing medicine | Inhibition rate |
| Blank control group | Distilled water | -- |
| Experimental group | Pharmaceutical preparation prepared in example 8 | 73.35％ |
| Control group 1 | Pharmaceutical preparation prepared in comparative example 1 | 38.57％ |
| Control group 2 | Pharmaceutical preparation prepared in comparative example 2 | 40.05％ |
| Control group 3 | Pharmaceutical preparation prepared in comparative example 3 | 1.28％ |
| Positive control group | Fluoroprednisone acetate cream on the market | 75.42％ |
As can be seen from Table 1, the pharmaceutical preparation prepared by the invention has a good inhibition effect on mouse auricle swelling caused by xylene, the inhibition effect is close to that of a commercially available fluocinolone acetonide cream, and the inhibition effect is obviously higher than that of a preparation which takes tiliroside and bletilla striata polysaccharide as active medicaments, so that the combination of tiliroside, bletilla striata polysaccharide and fluocinolone acetonide plays a role in synergy. In addition, the content of fluocinolone acetonide in the pharmaceutical preparation is obviously lower than that of the commercially available fluocinolone acetonide cream; therefore, the pharmaceutical preparation of the invention can effectively reduce the dosage of hormone and can effectively avoid symptoms such as dependent dermatitis and the like which are caused by long-term use.
2. Inhibition experiment of mouse abdominal capillary permeability increase caused by paraxylene by medicinal preparation for treating dermatitis
(1) Experimental drugs: the pharmaceutical preparation for treating dermatitis prepared in example 8 of the present invention, the pharmaceutical preparations prepared in comparative experiments 1 to 3, and the fluocinolone acetonide cream commercially available (the specification is 10g, and the amount of fluocinolone acetate in 10g of fluocinolone acetate cream is 2.5 mg).
(2) Test animals: SPF grade ICR mice were 48, male, and weighed 18-22 g.
(3) The test method comprises the following steps: the 48 mice were randomly divided into a blank control group, an experimental group, a control group 1, a control group 2, a control group 3 and a positive control group, 8 mice each. The same abdominal area of each group of mice had hair scraped off (area 2 x 2 cm)2) The corresponding medicaments of each group of mice in the table 2 are applied to the skin of the unhaired part of the abdomen of each group of mice 0.1g each time, and are sequentially applied in the morning and evening every day for continuous administration for 4 days. Injecting 0.5% Evans blue victory saline solution (0.1ml/10g B.W.) through tail vein of mouse 40min after the last drug application, immediately coating 30 μ l xylene on the skin with hair removed from mouse abdomen, treating with reagent 20min later, measuring absorbance value after 3 days, calculating inhibition rate of different drug preparations on mouse abdomen capillary permeability according to the absorbance value, and performing significance determination and comparison with model group by using t test method between groups. Specific results are shown in table 2. Wherein, the inhibition rate (blank control group absorbance value-administration group absorbance value)/blank control group is 100％。
TABLE 2 Effect of each pharmaceutical preparation on the permeability of mouse abdominal capillaries to xylene
| Group of | Smearing medicine | Inhibition rate |
| Blank control group | Distilled water | -- |
| Experimental group | Pharmaceutical preparation prepared in example 8 | 72.62％ |
| Control group 1 | Pharmaceutical preparation prepared in comparative example 1 | 42.39％ |
| Control group 2 | Pharmaceutical preparation prepared in comparative example 2 | 36.07％ |
| Control group 3 | Pharmaceutical preparation prepared in comparative example 3 | 1.45％ |
| Positive control group | Fluoroprednisone acetate cream on the market | 73.18％ |
As can be seen from Table 2, the inhibition effect of the pharmaceutical preparation prepared by the invention on the increase of permeability of capillary vessels in mouse abdomen caused by xylene is close to that of the commercially available fluocinolone acetonide cream, and the inhibition effect is obviously higher than that of the preparation which takes tiliroside and bletilla striata polysaccharide as active drugs alone, which indicates that the invention has a synergistic effect by compounding the tiliroside, the bletilla striata polysaccharide and the fluocinolone acetonide.
3. The medicinal preparation for treating dermatitis has the treatment effect on the pruritus of guinea pigs caused by histamine phosphate
(1) Experimental drugs: the pharmaceutical preparation for treating dermatitis prepared in example 8 of the present invention, the pharmaceutical preparations prepared in comparative experiments 1 to 3, and the fluocinolone acetonide cream commercially available (the specification is 10g, and the amount of fluocinolone acetate in 10g of fluocinolone acetate cream is 2.5 mg).
(2) The test method comprises the following steps: 30 guinea pigs (weighing 210-. The hair was scraped off from the same area of the dorsum of the right hind foot of each guinea pig group (area about 2 x 2 cm)2) The hair removal agent is cleaned and wiped dry, 0.1g of the agent corresponding to each group of guinea pigs in table 3 is applied to the skin of the hair removal part of each group of guinea pigs, and the agent is applied once in the morning and afternoon every day for 4 days. 2h after the application of the medicine on the 4 th day, the unhairing part is abraded to be red (without bleeding) by using sand paper, then the corresponding medicine is applied to the abraded part, and the corresponding medicine is applied again after 2h intervals; after the last application of the medicine, the wound surface is coated with 0.01% of histamine phosphate (50 mul/wound) for 15min, the subsequent dose is 50 mul/wound with increasing concentrations of 0.02%, 0.03% and 0.04% every 3min, and the total amount of histamine phosphate administered until the guinea pig licks the right foot back is the scratchiness threshold.
TABLE 3 Effect of the pharmaceutical formulations on histamine-phosphate-induced itching response
| Group of | Smearing medicine | Itch threshold (mug) |
| Blank control group | Distilled water | 0.18±0.14 |
| Experimental group | Pharmaceutical preparation prepared in example 8 | 0.86±0.23 |
| Control group 1 | Pharmaceutical preparation prepared in comparative example 1 | 0.37±0.09 |
| Control group 2 | Pharmaceutical preparation prepared in comparative example 2 | 0.46±0.32 |
| Control group 3 | Pharmaceutical preparation prepared in comparative example 3 | 0.19±0.19 |
| Positive control group | Fluoroprednisone acetate cream on the market | 0.91±0.16 |
As can be seen from Table 3, the itch threshold of the pharmaceutical preparation prepared by the invention is close to that of the commercially available fluocinonide cream, and is obviously higher than that of the preparation which takes tiliroside and bletilla striata polysaccharide as active medicines.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the present invention, but rather as the following description is intended to cover all modifications, equivalents and improvements falling within the spirit and scope of the present invention.
Claims (9)
1. A pharmaceutical composition is characterized by comprising tiliroside, bletilla polysaccharide and glucocorticoid, wherein the weight ratio of tiliroside to bletilla polysaccharide to glucocorticoid is (5-15): 3-12): 1.
2. The pharmaceutical composition of claim 1, wherein the weight ratio of tiliroside, bletilla polysaccharide and glucocorticoid is 10:8: 1.
3. the pharmaceutical composition of claim 1, wherein the glucocorticoid is fluocinolone acetonide or fluocinolone acetonide.
4. Use of a pharmaceutical composition according to any one of claims 1 to 3 for the manufacture of a medicament for the treatment of dermatitis.
5. A pharmaceutical preparation for treating dermatitis, which is prepared from the pharmaceutical composition of any one of claims 1 to 3 and pharmaceutically acceptable excipients.
6. The pharmaceutical formulation for treating dermatitis according to claim 5, wherein the pharmaceutical formulation is a cream, a solution, a gel, a liniment or a lotion.
7. The pharmaceutical preparation for treating dermatitis according to claim 6, wherein the pharmaceutical preparation is a cream, and the pharmaceutical preparation comprises the following components in parts by weight: 0.01-1 part of pharmaceutical composition, 0.5-1.6 parts of Transcutol P, 150.8-2.6 parts of Solutol HS, 6-12 parts of stearic acid, 6-15 parts of white vaseline, 5-12 parts of liquid paraffin, 2-12 parts of glycerol, 0.01-0.6 part of ethylparaben and 46-65 parts of water.
8. The dermatitis treatment preparation according to claim 7, wherein the pharmaceutical preparation comprises the following components in parts by weight: 0.24 part of pharmaceutical composition, 1 part of Transcutol P, 152 parts of Solutol HS, 7 parts of stearic acid, 10 parts of white vaseline, 8 parts of liquid paraffin, 8 parts of glycerol, 0.16 part of ethylparaben and 63.6 parts of water.
9. A method for preparing a pharmaceutical formulation for the treatment of dermatitis as claimed in claim 7 or 8, comprising the steps of:
(1) adding Solutol HS15, glycerol and ethylparaben into water in sequence, stirring and mixing uniformly, and heating to 60-70 ℃ to obtain an aqueous phase solution;
(2) dissolving the medicinal composition in Transcutol P to obtain a medicinal solution;
(3) mixing stearic acid, white vaseline and liquid paraffin, and heating to 65-75 deg.C to obtain oil phase solution;
(4) and (3) adding the oil phase solution obtained in the step (3) into the water phase solution, uniformly stirring, adding the medicinal solution prepared in the step (2), uniformly mixing, and condensing into paste to obtain the medicinal preparation for treating dermatitis.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114886823A (en) * | 2022-06-27 | 2022-08-12 | 珀莱雅化妆品股份有限公司 | Composition with anti-aging effect, glucide and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101795733A (en) * | 2007-08-13 | 2010-08-04 | 默克专利股份有限公司 | tyrosinase inhibitors |
| CN102379878A (en) * | 2011-07-15 | 2012-03-21 | 吉林敖东集团大连药业股份有限公司 | Pharmaceutical composition for treating dermatitis and eczema and preparation method thereof |
| WO2013138744A1 (en) * | 2012-03-16 | 2013-09-19 | M. Alphabet 1, Llc | Compositions for the treatment of skin disorders |
| US20170049807A1 (en) * | 2015-08-21 | 2017-02-23 | Cosmederm Bioscience, Inc. | Strontium based compositions and formulations for pain, pruritus, and inflammation |
-
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- 2021-12-30 CN CN202111681747.4A patent/CN114452297B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101795733A (en) * | 2007-08-13 | 2010-08-04 | 默克专利股份有限公司 | tyrosinase inhibitors |
| CN102379878A (en) * | 2011-07-15 | 2012-03-21 | 吉林敖东集团大连药业股份有限公司 | Pharmaceutical composition for treating dermatitis and eczema and preparation method thereof |
| WO2013138744A1 (en) * | 2012-03-16 | 2013-09-19 | M. Alphabet 1, Llc | Compositions for the treatment of skin disorders |
| US20170049807A1 (en) * | 2015-08-21 | 2017-02-23 | Cosmederm Bioscience, Inc. | Strontium based compositions and formulations for pain, pruritus, and inflammation |
Non-Patent Citations (2)
| Title |
|---|
| 仲维兰等: "银椴苷抑制人胰腺癌细胞增殖的作用及机制研究", 《中国药理学通报》, vol. 34, no. 12, pages 1679 * |
| 黄建: "妇康宁栓剂抗炎、抗菌试验的研究", 《国际医药卫生导报》, vol. 11, no. 10, pages 8 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114886823A (en) * | 2022-06-27 | 2022-08-12 | 珀莱雅化妆品股份有限公司 | Composition with anti-aging effect, glucide and preparation method thereof |
| CN114886823B (en) * | 2022-06-27 | 2023-10-13 | 珀莱雅化妆品股份有限公司 | Composition with anti-aging effect, and glycosyl body and preparation method thereof |
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| CN114452297B (en) | 2024-03-12 |
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