WO2017036241A1 - 一种祛痘中药组合物及其制备方法 - Google Patents

一种祛痘中药组合物及其制备方法 Download PDF

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Publication number
WO2017036241A1
WO2017036241A1 PCT/CN2016/087101 CN2016087101W WO2017036241A1 WO 2017036241 A1 WO2017036241 A1 WO 2017036241A1 CN 2016087101 W CN2016087101 W CN 2016087101W WO 2017036241 A1 WO2017036241 A1 WO 2017036241A1
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ethanol
preparation
aqueous solution
acne
chinese medicine
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English (en)
French (fr)
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刘光荣
邓文娟
唐健
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Infinitus China Co Ltd
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Infinitus China Co Ltd
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Priority to EP16840670.0A priority Critical patent/EP3342419B1/en
Priority to US15/538,104 priority patent/US9993510B2/en
Priority to JP2017537360A priority patent/JP6400851B2/ja
Publication of WO2017036241A1 publication Critical patent/WO2017036241A1/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • 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
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61P17/10—Anti-acne agents
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18

Definitions

  • the invention belongs to the field of traditional Chinese medicine, and particularly relates to a acne Chinese medicine composition and a preparation method thereof.
  • Acne also known as acne, acne, acne vulgaris, acne
  • Acne is a common skin disease that can cause inflammation of the sebaceous glands or hair follicles on human skin. When local lesions occur, it can produce white or milky white rice powder. Stinging pimples. The occurrence of acne is mainly related to factors such as excessive sebum secretion, clogging of hair follicle sebaceous gland ducts, bacterial infection and inflammatory reaction. After entering puberty, the levels of androgens, especially testosterone, increase rapidly, promoting the development of sebaceous glands and producing a large amount of sebum.
  • the abnormal keratinization of the hair follicle sebaceous gland duct causes the catheter to be blocked, and the sebum is discharged, forming a horny plug, that is, micro-acne.
  • Men and women with acne occur in adolescence, men are slightly more than women, but women are older than men. Hemorrhoids occur in the cheeks, forehead, cheeks, and nasolabial folds, followed by the chest, back, and shoulders. Acne skin lesions generally have no symptoms, inflammation can be accompanied by pain, can be divided into acne, papules, pustules, cyst nodules. 80-90% of adolescents have acne, which often declines or heals naturally after puberty, and individual patients can be extended to over 30 years of age. Although acne is a disease with self-healing tendency, the acne itself and the scar caused by the treatment of acne can seriously affect the quality of life of the patient, causing mental stress and economic burden of the patient, which needs attention.
  • Topical topical drugs vitamin A acid (vitamin A cream, adapalene gel, tazarotene gel), benzoyl peroxide, antibiotics (clindamycin, erythromycin, Chloramphenicol, etc.), azelaic acid, sulfur lotion, etc.;
  • oral antibiotics preferred tetracyclines (minocycline, doxycycline, etc.), followed by macrolides (erythromycin), avoid the choice of antibiotics commonly used to treat systemic infections such as levofloxacin, antibiotics Usually 6 to 12 weeks;
  • Oral isotretinoin is the standard treatment for severe acne, and it is also the most effective method for treating acne. The course of treatment is to achieve the minimum cumulative dose of 60mg/kg;
  • anti-androgen therapy such as oral contraceptive compound cyproterone acetate tablets (commercial name Da Ying -35), suitable for women with moderate and severe acne, accompanied by excessive androgen levels (such as hairy, sebum Oral contraceptives may also be considered in women with polycystic ovary syndrome, delayed acne, and significant exacerbations of acne before menstruation.
  • Oral glucocorticoids mainly used for fulminant or polymeric acne, following the principles of short-term, low-dose, combined with other methods;
  • the treatment of hemorrhoids also requires graded treatment: Grade 1: general topical treatment, preferred topical vitamin A acid preparation; Grade 2: combined with topical vitamin A acid and benzoyl peroxide or antibiotics, if necessary combined with oral antibiotics; : Combination therapy is often required, and oral antibiotics combined with topical benzoyl peroxide and/or retinoic acid are preferred.
  • Female patients with indications may also consider anti-androgen therapy; Level 4: Oral isotretinoin is the most effective treatment and can be used as first-line treatment. For patients with more inflammatory papules and pustules, antibiotics combined with topical benzoyl peroxide may be used first. After the lesions are significantly improved, oral isotretinoin sequential treatment is used.
  • an object of the present invention is to provide a acne Chinese medicine composition and a preparation method thereof.
  • the traditional Chinese medicine composition has obvious curative effect, high cure, natural mildness and long-term use in treating acne.
  • the present invention adopts the following technical solutions:
  • An acne Chinese medicine composition prepared from the following raw materials by weight:
  • the traditional Chinese medicine composition of the invention is made of mangosteen peel, thyme and clam shell, and the traditional Chinese medicines in the traditional Chinese medicine composition interact with each other, synergistically, antibacterial and anti-inflammatory.
  • mangosteen is Garcinia mangostana L., also known as hawthorn, mangosteen, and scorpion.
  • Mangosteen fruit is flat and sweet, can spleen and stimulate the body, and also has the effect of stopping diarrhea, while mangosteen peel is cool and bitter, and has anti-inflammatory and analgesic effects.
  • Thyme is known as ground pepper and thyme for the thyme thyme and the ground pepper (Xingkai thyme), which is used as a whole herb.
  • the clam shell is the dried immature fruit of the Citrus aurantium L. and its cultivar. When the peel is still green in July, it is cut into two halves from the middle, dried or dried at low temperature. Clam shell bitter, pungent, sour, warm, with the effect of wide qi, stagnation and swelling, attending chest qi stagnation, fullness of pain, food, sputum stop, stomach ptosis, rectal prolapse, sub-prolapse And other illnesses.
  • mangosteen peel, thyme and clam shell described in the present invention are well known to those skilled in the art. It can be purchased commercially from a pharmaceutical store or cultivated and harvested by the methods disclosed in the prior art, and the specifications are in accordance with national or industry standards.
  • the invention also provides a preparation method of the acne traditional Chinese medicine composition, which comprises 60-80 parts by weight of mangosteen peel, 10-20 parts by weight of thyme, 10-20 parts by weight of clam shell, ethanol extraction, and the extract is collected and purified.
  • the ethanol extraction is carried out by heating under reflux with 8-12 times by weight of a 76%-95% aqueous solution of ethanol for 1 h to 2.5 h.
  • the purifying comprises specifically the following steps:
  • the extract is filtered and concentrated, and the aqueous solution of ethanol is dissolved and refrigerated overnight;
  • the concentration in step a is preferably concentrated to a specific gravity of from 1.05 to 1.1.
  • the volume ratio of the ethanol in the aqueous solution of ethanol in step a is from 70% to 80%.
  • the aqueous solution of ethanol in step a is used in an amount from 4 to 6 times the weight of the concentrate.
  • the aqueous solution of the step a of ethanol is dissolved at a temperature of from 50 ° C to 80 ° C and a dissolution time of from 0.5 h to 2 h.
  • the refrigerating is placed at 0 to 4 ° C for 12 to 18 hours.
  • the eluent of step b is eluted as an aqueous solution of water, 20%-40% ethanol, and an aqueous solution of 60%-80% ethanol.
  • the eluate of the eluted portion of the aqueous solution of 60%-80% ethanol was collected.
  • the amount of water used is 1BV-2BV
  • the amount of aqueous solution of 20%-40% ethanol is 1BV-2BV
  • the amount of 60%-80% ethanol is 2BV-4BV;
  • the eluent in step b is eluted as water, 40% in sequence.
  • An aqueous solution of ethanol and an aqueous solution of 80% ethanol were eluted, and an eluate of an eluted portion of an aqueous solution of 80% ethanol was collected.
  • step b concentrates the eluate from which the aqueous portion of the aqueous solution of 60%-80% ethanol is collected and is dried.
  • the solution is concentrated to a specific gravity of 1.05-1.1 and then spray dried.
  • the filtering after step b further comprises the step of concentrating the solution.
  • the concentration is preferably up to a specific gravity of from 1.05 to 1.1.
  • the concentration in the preparation method of the present invention can be carried out by any known method.
  • the concentration in the preparation process of the invention is preferably concentrated under reduced pressure.
  • the specific conditions are temperature 60-80 ° C, vacuum degree ⁇ 0.08 Mpa.
  • the present invention also provides the invention also provides a prepared Chinese medicine composition.
  • the invention also provides a formulation of the traditional Chinese medicine composition.
  • the preparation may be a medicine or a skin care product.
  • the pharmaceutical preparation may be an external preparation known in the art, such as an elixir, an ointment, an emulsion, a paste, a film, a coating agent, a gel, an aerosol, a spray, a patch, and the like.
  • the skin care product can be of a type well known in the art, such as creams, lotions, serums, masks, eye creams, stock solutions, and the like.
  • the preparation of the traditional Chinese medicine composition of the present invention is a cream and a cream, which is easy to use, has strong pertinence, and has obvious curative effect.
  • the dosage and method of use of the pharmaceutical compositions and preparations of the present invention depend on a number of factors including the age, weight, sex, natural health status, nutritional status of the compound, the activity intensity of the compound, the time of use, the rate of metabolism, and the severity of the disease. And the subjective judgment of the doctor.
  • the dosage of the pharmaceutical composition preparation and the method of use can be easily determined by those skilled in the art based on the above factors.
  • the invention provides a acne Chinese medicine composition and a preparation method thereof.
  • the pharmaceutical composition is prepared from mangosteen peel, thyme and clam shell.
  • the traditional Chinese medicine composition of the present invention has good acne propionate.
  • the bactericidal effect and the anti-inflammatory effect of the bacillus, and the three medicinal materials have a synergistic effect on the anti-inflammatory effect, and the effect is fast and the effect is good.
  • the traditional Chinese medicine composition of the invention has natural raw materials, no pigment, preservative and any other auxiliary and functional additives. It is safe, mild, non-irritating, has no side effects, and can be used for a long time.
  • the preparation method of the traditional Chinese medicine composition of the invention does not use a toxic organic solvent, and only uses water and ethanol for extraction and dissolution steps, and the solvent can be repeatedly recovered and reused in the process, thereby saving cost and environmental protection effects.
  • the equipment used in the preparation method of the traditional Chinese medicine composition of the present invention for reflux extraction, filtration, concentration under reduced pressure, resin adsorption elution, spray drying is a simple equipment commonly used in traditional Chinese medicine preparations, and the process steps are easy to operate, and the product is The yield and the yield of active ingredients are high, which is suitable for industrial production.
  • Example 1 The acne Chinese medicine composition of the present invention
  • the mangosteen peel, thyme and clam shell are crushed separately, passed through a 60 mesh sieve, and mixed according to the mangosteen peel 80g, the thyme 20g, and the clam shell 20g ratio;
  • the above extract is filtered with a 100 mesh filter cloth to remove the dregs, concentrated under reduced pressure (temperature 60 ⁇ 80 ° C, vacuum ⁇ 0.08Mpa, the same below), to obtain a concentrate specific gravity of 1.08, weight 72g;
  • the concentration of the recovered ethanol-water solution is 80%, and the concentration of the ethanol-water solution: concentrate is 6:1, the solution is added to the concentrate, stirred at 80 ° C for 2 h, and refrigerated at 4 ° C for 18 h;
  • the cold storage liquid is filtered, and the filtrate is concentrated under reduced pressure to a specific gravity of 1.08, and the weight is 40 g;
  • the above concentrated liquid is adsorbed by using a polyamide resin, and is sequentially eluted with water, an aqueous solution of 40% ethanol, and an aqueous solution of 80% ethanol, and the amount of water used is 1 BV; the aqueous solution of 40% ethanol is used as 1 BV; 80% ethanol The amount of aqueous solution used is 4BV;
  • Example 2 The acne Chinese medicine composition of the present invention
  • mangosteen peel, thyme and clam shell are crushed separately, passed through 60 mesh sieve, and mixed according to mangosteen peel 60g, thyme 10g, clam shell 10g ratio;
  • the above extract is reduced by 100 mesh filter cloth to remove the dregs, concentrated under reduced pressure (temperature 60 ⁇ 80 ° C, vacuum ⁇ 0.08Mpa, the same below), to obtain a concentrate specific gravity of 1.08, weight 106g;
  • the recovered ethanol-water solution is prepared at a concentration of 60%, added to the concentrate according to the ratio of ethanol-aqueous solution: concentrate volume ratio of 4:1, stirred and dissolved at 50 ° C for 0.5 h, and refrigerated at 0 ° C for 12 h;
  • the cold storage liquid is filtered, and the filtrate is concentrated under reduced pressure to a specific gravity of 1.08, and the weight is 76 g;
  • the above concentrated liquid is adsorbed by using a polyamide resin, and sequentially eluted with water, an aqueous solution of 40% ethanol, and an aqueous solution of 80% ethanol, and the amount of water used is 2 BV; the aqueous solution of 40% ethanol is used as 2 BV; 80% ethanol The amount of aqueous solution used is 2BV;
  • Example 3 The acne Chinese medicine composition of the present invention
  • the above extract is reduced by 100 mesh filter cloth to remove the dregs, concentrated under reduced pressure (temperature 60 ⁇ 80 ° C, vacuum ⁇ 0.08Mpa, the same below), to obtain a concentrate specific gravity of 1.06, weight 106g;
  • the recovered ethanol-water solution is prepared at a concentration of 70%, and is added to the concentrated liquid according to the ratio of the ethanol-aqueous solution: the concentrated liquid is 5:1; the mixture is stirred and dissolved at 60 ° C for 1.5 hours, and refrigerated at 2 ° C for 15 hours;
  • the cold storage liquid is filtered, and the filtrate is concentrated under reduced pressure to a specific gravity of 1.08, and the weight is 76 g;
  • the above concentrated liquid is adsorbed by using a polyamide resin; the water is used in an aqueous solution of 40% ethanol and an aqueous solution of 80% ethanol, and the amount of water used is 1 BV; the aqueous solution of 40% ethanol is used as 2 BV; 80% ethanol The amount of aqueous solution used is 3BV;
  • the above extract is reduced by 100 mesh filter cloth to remove the dregs, concentrated under reduced pressure (temperature 60 ⁇ 80 ° C, vacuum ⁇ 0.08Mpa, the same below), to obtain a concentrate specific gravity of 1.06, weight 62g;
  • the recovered ethanol-water solution is prepared at a concentration of 70%, and is added to the concentrated liquid according to the ratio of the ethanol-aqueous solution: the concentrated liquid is 5:1; the mixture is stirred and dissolved at 60 ° C for 1.5 hours, and refrigerated at 2 ° C for 15 hours;
  • the above concentrated liquid is adsorbed by using a polyamide resin, and sequentially eluted with water, an aqueous solution of 40% ethanol, and an aqueous solution of 80% ethanol, and the amount of water used is 1 BV; the aqueous solution of 40% ethanol is used as 2 BV; 80% ethanol The amount of aqueous solution used is 3BV;
  • the above extract is reduced by 100 mesh filter cloth to remove the dregs, concentrated under reduced pressure (temperature 60 ⁇ 80 ° C, vacuum ⁇ 0.08Mpa, the same below), to obtain a concentrate specific gravity of 1.06, weight 52g;
  • the recovered ethanol-water solution is prepared at a concentration of 70%, and is added to the concentrated liquid according to the ratio of the ethanol-aqueous solution: the concentrated liquid is 5:1; the mixture is stirred and dissolved at 60 ° C for 1.5 hours, and refrigerated at 2 ° C for 15 hours;
  • the cold storage liquid is filtered, and the filtrate is concentrated under reduced pressure to a specific gravity of 1.08, and the weight is 38 g;
  • the above concentrated liquid is adsorbed by using a polyamide resin, and sequentially eluted with water, an aqueous solution of 40% ethanol, and an aqueous solution of 80% ethanol, and the amount of water used is 1 BV; the aqueous solution of 40% ethanol is used as 2 BV; 80% ethanol The amount of aqueous solution used is 3BV;
  • the above extract is reduced by 100 mesh filter cloth to remove the dregs, concentrated under reduced pressure (temperature 60 ⁇ 80 ° C, vacuum ⁇ 0.08Mpa, the same below), to obtain a concentrate specific gravity of 1.06, weight 70g;
  • the recovered ethanol-water solution is prepared at a concentration of 70%, and is added to the concentrated liquid according to the ratio of the ethanol-aqueous solution: the concentrated liquid is 5:1; the mixture is stirred and dissolved at 60 ° C for 1.5 hours, and refrigerated at 2 ° C for 15 hours;
  • the cold storage liquid is filtered, and the filtrate is concentrated under reduced pressure to a specific gravity of 1.08, and the weight is 58 g;
  • the above concentrated liquid is adsorbed by using a polyamide resin, and sequentially eluted with water, an aqueous solution of 40% ethanol, and an aqueous solution of 80% ethanol, and the amount of water used is 1 BV; the aqueous solution of 40% ethanol is used as 2 BV; 80% ethanol The amount of aqueous solution used is 3BV;
  • test strain is Propionibacterium acnes (ATCC 6919).
  • D1 to D6 correspond to the products prepared in Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3, respectively.
  • medium P. acnes culture medium
  • the pH is adjusted to 6.6 ⁇ 7.0.
  • Agar 15g/L was added to the solid medium.
  • 0.1 ml of the frozen-preserved bacterial suspension was taken in 5 ml of P. acnes liquid medium, and cultured at 37 ° C for 2 days under anaerobic conditions to obtain an experimental bacterial suspension.
  • D1, D2, D3, D4, D5, and D6 were diluted with physiological saline to a test concentration of 0.1%, respectively, and then diluted by a gradient.
  • the gradient dilutions of the first test were 100% (sample stock), 50%, 25%, 12.5%, 6.25%, 3.125%, 1.56%, 0.78%, respectively.
  • the gradient dilution concentrations were 10%, 8%, 6%, 4%, and 2%, respectively.
  • the bacterial suspension was diluted with P. acnes liquid medium to a final bacterial concentration of 10 6 CFU/ml.
  • the effect of inhibiting P. acnes can be substantially achieved by adding at least 0.01% of the finished product of the traditional Chinese medicine composition of the present invention, and the traditional Chinese medicine of the present invention
  • the composition has a stronger bacteriostatic effect than the use of a single medicinal herb.
  • Test Example 2 Anti-inflammatory efficacy test of mouse dermatitis model
  • mice Balb/c mice, female, 8 weeks old, weighing 20-25 g, purchased from Shanghai Slack Laboratory Animals Co., Ltd., license number SCXK (Shanghai) 2007-9005.
  • mice in each group were depilated on the back, the area was about 2 cm ⁇ 2 cm, and 100 ⁇ L of 7% DNCB acetone solution was applied to the back of the mouse to be sensitized with the sampler, starting at d5, in the right ear of the mouse.
  • the internal test was applied with 20 ⁇ L of 0.1% DNCB solution and challenged once every 3 days for 5 times to induce chronic dermatitis.
  • different concentrations of D1-D6 dilutions or solvents were applied to the right ear and back skin sensitization area after the first challenge, twice daily, after each challenge.
  • mice were sacrificed 48 h after the last challenge, and the left and right ears (about 8 mm in diameter) were removed with a puncher. The mass was weighed on the analytical balance, and the difference in mass between the ears was calculated to indicate ear swelling.
  • mice were randomly divided into groups of 4, and each experiment was set up with 5 experimental groups, which were normal control groups: the back shearing area and the right ear were only coated with acetone; the solvent control group: the back shearing area and the right ear.
  • Applying DNCB acetone solution to induce dermatitis the solvent for applying the test component after the first challenge (distributing D1-D6 to 0.1% aqueous solution); 5%, 10% and 15% D1-D6 dilution component administration group: back shearing
  • the area and right ear were coated with DNCB acetone solution to induce dermatitis.
  • the components to be tested were applied at concentrations of 5%, 10% and 15%, respectively.
  • the acne Chinese medicine composition according to the embodiment 1 of the present invention is added to a common matrix cream according to 0.1%, and is applied to the affected part of the subject, and the marked redness is relieved in 0.5-1 hour, and the 4-6 hour is no longer used. There is a feeling of swelling and tingling and other bad feelings caused by hemorrhoids, and there are wounds that are scarred within 24 hours. After prolonged use of acne sufferers, the distribution of acne on the face is greatly reduced, and the inflammation is milder than that of the general population.
  • the clinical effects of the acne Chinese herbal composition described in Example 2 and Example 3 were comparable to those of Example 1.

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Abstract

一种祛痘中药组合物及其制备方法，所述中药组合物由山竹果皮、百里香和枳壳为原料，经过乙醇提取、大孔树脂等步骤，收集60%-80%乙醇洗脱部分制成，所述三种药材在抗炎功效上有协同作用。

Description

一种祛痘中药组合物及其制备方法
本申请要求于2015年8月28日提交中国专利局、申请号为201510540785.6、发明名称为“一种祛痘中药组合物及其制备方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明属于中医药领域，具体涉及一种祛痘中药组合物及其制备方法。
背景技术
痤疮(又叫青春痘、粉刺、寻常性痤疮、暗疮)，是一种常见皮肤疾病，能造成人体皮肤上皮脂腺或毛囊的发炎，局部病变时会产生能挤出白色或乳白色碎米样粉汁的刺状丘疹。痤疮的发生主要与皮脂分泌过多、毛囊皮脂腺导管堵塞、细菌感染和炎症反应等因素密切相关。进入青春期后人体内雄激素特别是睾酮的水平迅速升高，促进皮脂腺发育并产生大量皮脂。同时毛囊皮脂腺导管的角化异常造成导管堵塞，皮脂排出障碍，形成角质栓即微粉刺。毛囊中多种微生物尤其是痤疮丙酸杆菌大量繁殖，痤疮丙酸杆菌产生的脂酶分解皮脂生成游离脂肪酸，同时趋化炎症细胞和介质，最终诱导并加重炎症反应。
痤疮好发于青春期的男性和女性，男性略多于女性，但女性发病早于男性。痤疮好发于面颊、额部、颊部和鼻唇沟，其次是胸部、背部和肩部。痤疮皮损一般无自觉症状，炎症明显时可伴有疼痛，可分为粉刺、丘疹、脓疱、囊肿结节。有80-90％的青少年患过痤疮，青春期后往往能自然减退或痊愈，个别患者也可延长到30岁以上。虽然痤疮是有自愈倾向的疾病，但是痤疮本身以及痤疮治疗不及时引起的瘢痕可以严重影响患者的生活质量，造成患者的精神压力和经济负担，需引起关注。
痤疮治疗的常用方法有六种：
(1)局部外用药物：维A酸类(维A酸乳膏、阿达帕林凝胶、他扎罗汀凝胶)、过氧化苯甲酰、抗生素类(克林霉素、红霉素、氯霉素等)、壬二酸、硫磺洗剂等；
(2)口服抗生素：首选四环素类(米诺环素、多西环素等)，其次为大环内酯类(红霉素)，避免选择常用于治疗系统感染的抗生素如左氧氟沙星等，抗生素疗程通常6～12周；
(3)口服异维A酸：对于严重的痤疮，口服异维A酸是标准疗法，也是目前治疗痤疮最有效的方法，疗程以达到最小累积剂量60mg/kg为目标；
(4)抗雄激素治疗：如口服避孕药复方醋酸环丙孕酮片(商品名达英-35)，适用于女性中、重度痤疮患者，伴有雄激素水平过高表现(如多毛、皮脂溢出等)或多囊卵巢综合征，迟发型痤疮及月经期前痤疮显著加重的女性患者也可考虑应用口服避孕药，
(5)口服糖皮质激素：主要用于暴发性或聚合性痤疮，遵循短期、小剂量、与其他方法联合应用的原则；
(6)其他：对于不能耐受或不愿接受药物治疗的患者，还可考虑物理治疗，如光动力疗法(PDT)、果酸疗法、激光治疗等。
痤疮的治疗还需要分级治疗：1级：一般采用局部治疗，首选外用维A酸类制剂；2级：联合外用维A酸类及过氧化苯甲酰或抗生素，必要时联合口服抗生素；3级：常常需要联合治疗，口服抗生素联合外用过氧化苯甲酰和/或维A酸类药物为首选。有指征的女性患者也可考虑抗雄激素治疗；4级：口服异维A酸是最有效的治疗方法，可作为一线治疗。对于炎性丘疹和脓疱较多者，也可先系统应用抗生素联合外用过氧化苯甲酰，待皮损明显改善后再改用口服异维A酸序贯治疗。
然而目前各种用于治疗痤疮的药物中，西药占据了极大的比重，这类药虽然能达到祛痘的效果，但是其副作用也相对较大，不宜长期使用，且其使用量也不宜过大。对于青春期到成人这个年龄段痤疮多 发、反复发作的人群来说，更需要天然温和，副作用小，可以长期使用的祛痘产品。
发明内容
有鉴于此，本发明的目的在于提供一种祛痘中药组合物及其制备方法。所述中药组合物治疗痤疮疗效显著、治愈高，天然温和，可以长期使用。
为实现本发明的目的，本发明采用如下技术方案：
一种祛痘中药组合物，由如下重量份的原料制成：
山竹果皮  60份-80份
百里香    10份-20份
枳壳      10份-20份。
本发明所述中药组合物选用山竹果皮、百里香和枳壳三味药材制成，所述中药组合物中各味中药相互影响，协同作用，抗菌、消炎。
其中，山竹学名莽吉柿(Garcinia mangostana L.)，又名山竺、山竹子、倒捻子。山竹果性平味甘酸，能够健脾生津，还具有止泻的作用，而山竹果皮则性凉味苦，具有消炎止痛的作用。
百里香别名地椒、麝香草为唇形科百里香属植物百里香和地椒(兴凯百里香)，以全草入药。夏季枝叶茂盛时采收，拔起全株，洗净，剪去根部(可供栽培繁殖)，切段，鲜用或晒干。性微温，味辛，具有祛风解表、行气止痛、止咳、降压之功效，主要用于感冒、咳嗽、头痛、牙痛、消化不良、急性胃肠炎和高血压病。
枳壳为芸香科植物酸橙Citrus aurantium L.及其栽培变种的干燥未成熟果实。7月果皮尚绿时采收，自中部横切为两半，晒干或低温干燥。枳壳性苦、辛、酸、温，具有理气宽中、行滞消胀的功效，主治胸胁气滞、胀满疼痛、食积不化、痰饮内停、胃下垂、脱肛、子官脱垂等病症。
本发明中所述的山竹果皮、百里香和枳壳是本领域技术人员公知 的，可以通过商业途径从医药商店购买得到或通过现有技术中公开的方法栽培、采收得到，其规格符合国家或行业标准即可。
本发明还提供了所述祛痘中药组合物的制备方法，取60-80重量份山竹果皮、10-20重量份百里香、10-20重量份枳壳混合，乙醇提取，收集提取液，纯化。
按照本发明，在一些实施方案中，本发明所述制备方法中，所述乙醇提取为用8-12倍重量的76％-95％乙醇水溶液加热回流提取1h-2.5h。
按照本发明，在一些实施方案中，本发明所述制备方法中，所述纯化具体为包括以下步骤：
a、提取液过滤后浓缩，乙醇的水溶液溶解后冷藏放置过夜；
b、过滤，滤液大孔树脂吸附，洗脱液洗脱。
其中，在一些实施方案中，步骤a所述浓缩优选为浓缩至比重1.05～1.1。
在一些实施方案中，步骤a所述乙醇的水溶液中所述乙醇的体积比为70％-80％。
进一步的，在一些实施方案中，步骤a所述乙醇的水溶液的使用的量为浓缩液重量的4倍-6倍。
在一些实施方案中，步骤a乙醇的水溶液溶解浓缩液的溶解温度为50℃-80℃，溶解时间为0.5h-2h。
在一些实施方案中，步骤a所述冷藏放置过夜为0～4℃放置12h～18h。
按照本发明，在一些实施方案中，本发明所述制备方法中，步骤b所述洗脱液洗脱为依次用水、20％-40％乙醇的水溶液、60％-80％乙醇的水溶液洗脱，收集60％-80％乙醇的水溶液洗脱部分的洗脱液。
其中，水的使用量为1BV-2BV，20％-40％乙醇的水溶液的使用量为1BV-2BV；60％-80％乙醇的使用量为2BV-4BV；
在一些具体实施例中，步骤b所述洗脱液洗脱为依次用水、40％ 乙醇的水溶液、80％乙醇的水溶液洗脱，收集80％乙醇的水溶液洗脱部分的洗脱液。
按照本发明，在一些实施方案中，本发明所述制备方法中，步骤b将收集60％-80％乙醇的水溶液洗脱部分的洗脱液浓缩后干燥。在一些具体实施例中，浓缩至比重1.05-1.1后进行喷雾干燥。
在一些优选实施方案中，步骤b所述过滤后还包括对溶液进行浓缩的步骤。所述浓缩优选至比重1.05～1.1。
本领域技术人员可以理解，本发明所述制备方法中所述浓缩可以采用任何已知的方法进行。在一些具体实施例中，本发明所述制备方法中所述浓缩优选为减压浓缩。具体条件为温度60～80℃，真空度≥0.08Mpa。
本发明还提供了发明还提供了制备的中药组合物。
本发明还提供了所述中药组合物的制剂。其中，所述制剂可以为药物或护肤品。所述药品可以本领域公知的外用制剂，如搽剂、软膏剂、乳剂、糊剂、膜剂、涂膜剂、凝胶剂、气雾剂、喷雾剂、贴剂等等。所述护肤品可以本领域公知的类型，如面霜，乳液、精华液、面膜、眼霜、原液等等。
本领域技术人员可以根据不同使用者的需求将本发明所述中药组合物加入制备不同剂型是所需的各种常规的辅料，以常规制剂方法，经常规加工制成上述常用制剂。
优选的，本发明所述中药组合物的制剂为膏剂和霜剂，易于使用，针对性强，疗效明显。
本发明的药物组合物及制剂的使用剂量和使用方法取决于诸多因素，包括使用者的年龄、体重、性别、自然健康状况、营养状况、化合物的活性强度、使用时间、代谢速率、病程严重程度以及诊治医师的主观判断。本领域的技术人员根据上述因素可以容易地决定药物组合物制剂的使用剂量和使用方法。
本发明提供了一种祛痘中药组合物及其制备方法。本发明所述中 药组合物由山竹果皮、百里香和枳壳为原料制备而成，经过小鼠皮炎模型抗炎功效测试以及痤疮丙酸杆菌的抑菌实验，证明本发明所述中药组合物具有良好的痤疮丙酸杆菌抑制效果以及抗炎功效，且这三种药材在抗炎功效上具有协同作用，起效快、效果好。本发明所述中药组合物原料药材天然，不含色素、防腐剂以及其他任何辅助类和功效性添加剂，安全温和、无刺激性，无副作用，可以长期使用，广泛适用于青春期或成年期长期受到痤疮困扰的人群。本发明所述中药组合物的制备方法不使用有毒的有机溶剂，仅使用水和乙醇进行提取和溶解等步骤，在过程中还可反复回收再利用溶剂，起到节约成本和环保的效果。本发明所述中药组合物的制备方法中所使用的回流提取、过滤、减压浓缩、树脂吸附洗脱、喷雾干燥所用的设备均是中药制剂常用的简单设备，且工艺步骤容易操作，产品的得率以及有效成分的得率高，适合产业化生产。
具体实施方式
下面将结合本发明实施例，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
为了进一步理解本发明，下面结合实施例对本发明提供进行详细说明。
实施例1：本发明所述祛痘中药组合物
1、将山竹果皮、百里香、枳壳分别粉碎，过60目筛，按山竹果皮80g，百里香20g，枳壳20g比例混合；
2、用12倍药材重量的95％乙醇-水溶液回流提取2.5h；
3、将上述提取液用100目滤布滤去药渣，减压浓缩(温度60～80℃，真空度≥0.08Mpa，下同)，得到浓缩液比重1.08，重量72g；
4、将回收的乙醇-水溶液配制浓度为80％，按乙醇-水溶液：浓缩液的体积比为6:1的比例加入浓缩液中，80℃搅拌溶解2h，4℃冷藏过夜18h；
5、冷藏液过滤，滤液减压浓缩至比重1.08，重量为40g；
6、使用聚酰胺树脂对上述浓缩液进行吸附，依次用水、40％乙醇的水溶液、80％乙醇的水溶液洗脱，水的使用量为1BV；40％乙醇的水溶液使用量为1BV；80％乙醇的水溶液使用量为4BV；
7、收集80％乙醇的水溶液洗脱的洗脱液，减压浓缩至比重1.06，喷雾干燥得5.04g。
实施例2：本发明所述祛痘中药组合物
1、将山竹果皮、百里香、枳壳分别粉碎，过60目筛，按山竹果皮60g，百里香10g，枳壳10g比例混合；
2、用8倍药材重量的60％乙醇-水溶液回流提取1h；
3、将上述提取液减用100目滤布滤去药渣，减压浓缩(温度60～80℃，真空度≥0.08Mpa，下同)，得到浓缩液比重1.08，重量106g；
4、将回收的乙醇-水溶液配制浓度为60％，按乙醇-水溶液：浓缩液的体积比为4:1的比例加入浓缩液中，50℃搅拌溶解0.5h，0℃冷藏过夜12h；
5、冷藏液过滤，滤液减压浓缩至比重1.08，重量为76g；
6、使用聚酰胺树脂对上述浓缩液进行吸附，依次用水、40％乙醇的水溶液、80％乙醇的水溶液洗脱，水的使用量为2BV；40％乙醇的水溶液使用量为2BV；80％乙醇的水溶液使用量为2BV；
7、收集80％乙醇的水溶液洗脱的洗脱液，减压浓缩至比重1.06，喷雾干燥得3.2g。
实施例3：本发明所述祛痘中药组合物
1、将山竹果皮、百里香、枳壳分别粉碎，过60目筛，按山竹果 皮80g，百里香10g，枳壳10g比例混合；
2、用10倍药材重量的75％乙醇-水溶液回流提取2h；
3、将上述提取液减用100目滤布滤去药渣，减压浓缩(温度60～80℃，真空度≥0.08Mpa，下同)，得到浓缩液比重1.06，重量106g；
4、将回收的乙醇-水溶液配制浓度为70％，按乙醇-水溶液：浓缩液的体积比为5:1的比例加入浓缩液中，60℃搅拌溶解1.5h，2℃冷藏过夜15h；
5、冷藏液过滤，滤液减压浓缩至比重1.08，重量为76g；
6、使用聚酰胺树脂对上述浓缩液进行吸附；依次用水、40％乙醇的水溶液、80％乙醇的水溶液洗脱，水的使用量为1BV；40％乙醇的水溶液使用量为2BV；80％乙醇的水溶液使用量为3BV；
7、收集80％乙醇的水溶液洗脱的洗脱液，减压浓缩至比重1.06，喷雾干燥得4.4g。
对比例1
1、将山竹果皮100g粉碎，过60目筛；
2、用10倍药材重量的75％乙醇-水溶液回流提取2h；
3、将上述提取液减用100目滤布滤去药渣，减压浓缩(温度60～80℃，真空度≥0.08Mpa，下同)，得到浓缩液比重1.06，重量62g；
4、将回收的乙醇-水溶液配制浓度为70％，按乙醇-水溶液：浓缩液的体积比为5:1的比例加入浓缩液中，60℃搅拌溶解1.5h，2℃冷藏过夜15h；
5、冷藏液过滤，滤液减压浓缩至比重1.08，重量为54g；
6、使用聚酰胺树脂对上述浓缩液进行吸附，依次用水、40％乙醇的水溶液、80％乙醇的水溶液洗脱，水的使用量为1BV；40％乙醇的水溶液使用量为2BV；80％乙醇的水溶液使用量为3BV；
7、收集80％乙醇的水溶液洗脱的洗脱液，减压浓缩至比重1.08，喷雾干燥4.0。
对比例2
1、将百里香皮100g粉碎，过60目筛；
2、用10倍药材重量的75％乙醇-水溶液回流提取2h；
3、将上述提取液减用100目滤布滤去药渣，减压浓缩(温度60～80℃，真空度≥0.08Mpa，下同)，得到浓缩液比重1.06，重量52g；
4、将回收的乙醇-水溶液配制浓度为70％，按乙醇-水溶液：浓缩液的体积比为5:1的比例加入浓缩液中，60℃搅拌溶解1.5h，2℃冷藏过夜15h；
5、冷藏液过滤，滤液减压浓缩至比重1.08，重量为38g；
6、使用聚酰胺树脂对上述浓缩液进行吸附，依次用水、40％乙醇的水溶液、80％乙醇的水溶液洗脱，水的使用量为1BV；40％乙醇的水溶液使用量为2BV；80％乙醇的水溶液使用量为3BV；
7、收集80％乙醇的水溶液洗脱的洗脱液，减压浓缩至比重1.06，喷雾干燥得1.2g。
对比例3
1、将枳壳100g粉碎，过60目筛；
2、用10倍药材重量的75％乙醇-水溶液回流提取2h；
3、将上述提取液减用100目滤布滤去药渣，减压浓缩(温度60～80℃，真空度≥0.08Mpa，下同)，得到浓缩液比重1.06，重量70g；
4、将回收的乙醇-水溶液配制浓度为70％，按乙醇-水溶液：浓缩液的体积比为5:1的比例加入浓缩液中，60℃搅拌溶解1.5h，2℃冷藏过夜15h；
5、冷藏液过滤，滤液减压浓缩至比重1.08，重量为58g；
6、使用聚酰胺树脂对上述浓缩液进行吸附，依次用水、40％乙醇的水溶液、80％乙醇的水溶液洗脱，水的使用量为1BV；40％乙醇的水溶液使用量为2BV；80％乙醇的水溶液使用量为3BV；
7、收集80％乙醇的水溶液洗脱的洗脱液，减压浓缩至比重1.05，喷雾干燥得1.8g。
试验例1：抑菌效果：
1、材料
1.1、试验菌株为痤疮丙酸杆菌(ATCC6919)。
1.2、中药组合物样品：D1、D2、D3、D4、D5、D6样品，4℃存放备用。其中D1至D6依次对应实施例1、2、3和对照例1、2、3制备的产品。
1.3、培养基：痤疮丙酸杆菌培养基，调节pH为6.6～7.0。其中固体培养基中加入琼脂15g/L。
2、方法
2.1、菌悬液制备及接种
取冷冻保藏菌悬液0.1ml于5ml痤疮丙酸杆菌液体培养基中，于37℃厌氧条件培养2d，为实验菌悬液。
2.2、药液制备：将D1、D2、D3、D4、D5、D6分别用生理盐水稀释成试验浓度0.1％，然后分别梯度稀释。第一次试验梯度稀释浓度分别为100％(样品原液)、50％、25％、12.5％、6.25％、3.125％、1.56％、0.78％。第二次试验复测梯度稀释浓度分别为10％、8％、6％、4％、2％。
2.3、菌液制备
用痤疮丙酸杆菌液体培养基稀释菌悬液，使其最终菌浓度为l06CFU/ml。
2.4、培养及结果判读：在微孔中加入菌液100μL和药液100μL，同时设不加菌的阴性对照和不加药液的正常生长对照，每种药做3个平行，取平均值。置37℃厌氧孵育，48h后观察结果。采用肉眼判断有无浑浊，采用直接法读取数据。结果判断的前提是生长对照良好，空白对照无菌生长清晰，其它孔随药物浓度梯度升高而菌的生长受到抑 制。
表1 第一次抑菌梯度试验结果
浓度梯度 D1 D2 D3 D4 D5 D6
50％ - - - - - -
25％ - - - - + +
12.5％ - - - + + +
6.25％ + + + + + +
3.125％ + + + + + +
1.56％ + + + + + +
0.78％ + + + + + +
注：其中+代表有菌生长，-代表无。
表2 第二次抑菌梯度试验结果
浓度梯度 D1 D2 D3 D4
10％ - - - +
8％ - + - +
6％ + + + +
4％ + + + +
2％ + + + +
1％ + + + +
注：其中+代表有菌生长，-代表无。
2.5、结果：
从表1结果可见，3组实施例0.1％的溶液，均在其稀释至12.5％浓度及以上，对痤疮丙酸杆菌有良好抑制作用，而对照例中D4在25％稀释液及以上才能达到效果，D5及D6则需要50％浓度以上。从表2结果可见，经过验证，D1、D3的抑菌浓度可在8％稀释液达到，而D2也在10％的浓度达到了抑菌效果。
由上述结果可知，最低添加本发明所述中药组合物成品约0.01％，即可基本达到抑制痤疮丙酸杆菌的效果，且本发明所述中药 组合物比单味药材使用具有更强的抑菌效果。
试验例2：小鼠皮炎模型抗炎功效测试
1、实验材料和方法：
1.1、实验动物：Balb/c小鼠，雌性，8周龄，体重20-25g，购自上海斯莱克实验动物有限责任公司，许可证号为SCXK(沪)2007-9005。
1.2、主要实验试剂:2，4-二硝基氯苯(2，4-dinitrochlorobenzene,DNCB)，分析纯，购自上海顺强生物科技有限公司；丙酮(acetone)，分析纯，购自国药集团化学试剂有限公司。
2、DNCB诱导的慢性皮炎湿疹小鼠模型和药物治疗方法：
实验开始当天(d0)，将各组小鼠背部去毛，面积约2cm×2cm，用加样器量取7％DNCB丙酮溶液100μL涂抹于小鼠背部剪毛区致敏，d5开始，在鼠右耳内测涂抹0.1％DNCB溶液20μL激发，每3日激发1次，共5次，诱导慢性皮炎。为评价D1-D6的抗皮炎效应，分别于首次激发后开始将不同浓度的组分D1-D6稀释液或溶剂涂于右耳和背部皮肤致敏区，每日2次，于每次激发后48h观察皮炎模型组和药物治疗组小鼠背部致敏区皮损情况。于末次激发后48h处死全部小鼠，用打孔器取下左右耳片(直径8mm左右)，在分析天平上称量质量，计算两耳质量差表示耳肿胀度。
3、实验结果：
3.1、D1-D6抗皮炎效应的初步评价结果：
将小鼠随机分组，每组4只，每个组分的评价实验设置5个实验组，分别为正常对照组：背部剪毛区和右耳仅涂抹丙酮；溶剂对照组：背部剪毛区和右耳涂抹DNCB丙酮溶液诱发皮炎，首次激发后涂抹待测组分的溶剂(将D1-D6配置为0.1％水溶液)；5％，10％和15％D1-D6稀释液组分给药组：背部剪毛区和右耳涂抹DNCB丙酮溶液诱发皮炎，首次激发后涂抹待测组分，浓度分别为5％，10％和15％。 于每次激发后48h观察各实验组小鼠背部致敏区皮损情况，拍摄照片。结果表明组分D5和组分D6在5-15％剂量范围内基本没有缓解皮炎的药理效应，而组分D1-D4在15％剂量时具有一定的缓解皮炎的药理效应，结果如表3。
表3 D1-D6稀释液小鼠模型耳肿胀数据表
Figure PCTCN2016087101-appb-000001
从表3数据可知D1-D4 0.1％的溶液，其不同浓度均有缓解验证的作用，但是5％浓度效果不明显，10％浓度略有起效，15％浓度效果较明显。纵向比较，D1、D2、D3效果整体相近，比D4略好，而D5、D6因背部炎症没有明显缓解，不做比较。
由抑菌实验结果可见，D3最低使用浓度可达8％，而D4最低使用浓度要高于12.5％；在小鼠炎症模型耳肿胀差量数据表中可以看出，D3和D4两组溶液在5％浓度时缓解炎症效果相近，但是在10％和15％浓度时，D3的数据明显小于D4，其差值高于20％，说明了D3的抗炎效果在同浓度远胜于D4，表明山竹果皮、百里香、枳壳3种中药在抑菌、舒缓炎症上有协同作用。
试验例3：临床实验
将本发明实施例1所述祛痘中药组合物按照0.1％添加至普通基质膏霜中，涂抹在受测者的患处，明显红肿的在0.5-1小时即缓解症状，4-6小时不再有肿胀感和刺痛感等痤疮带来的不良感觉，有创口的在24小时内均结痂。长期受到痤疮困扰的受试者在长期使用后，痤疮在脸部的分布密度大大下降，且发病时其炎症较普通人群轻。而实施例2和实施例3所述祛痘中药组合物的临床效果与实施例1相当。

Claims (10)

  1. 一种祛痘中药组合物，由如下重量份的原料制成：
    山竹果皮  60份-80份
    百里香    10份-20份
    枳壳      10份-20份。
  2. 一种祛痘中药组合物的制备方法，取60-80重量份山竹果皮、10-20重量份百里香、10-20重量份枳壳混合，乙醇提取，收集提取液，纯化。
  3. 根据权利要求2所述的制备方法，所述乙醇提取为用8-12倍重量的76％-95％乙醇水溶液加热回流提取1h-2.5h。
  4. 根据权利要求2或3所述的制备方法，所述纯化具体为包括以下步骤
    a、提取液过滤后浓缩，乙醇的水溶液溶解后冷藏放置过夜；
    b、过滤，滤液大孔树脂吸附，洗脱液洗脱。
  5. 根据权利要求4所述的制备方法，步骤a所述浓缩为浓缩至比重1.05～1.1。
  6. 根据权利要求4或5所述的制备方法，步骤a所述乙醇的水溶液中所述乙醇的体积比为70％-80％。
  7. 根据权利要求4-6任意一项所述的制备方法，步骤a所述冷藏放置过夜为0～4℃放置12h～18h。
  8. 根据权利要求4-7任意一项所述的制备方法，步骤b所述洗脱液洗脱为依次用水、20％-40％乙醇的水溶液、60％-80％乙醇的水溶液洗脱，收集60％-80％乙醇的水溶液洗脱部分的洗脱液。
  9. 权利要求2-8所述制备方法制备的中药组合物。
  10. 一种祛痘的制剂，其特征在于，由权利要求1或9所述的中药组合物及可接受的辅料制成。
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