Composition for treatment of scars skin disease

Composition for treating skin diseases including scars

The present invention relates to a method for treating scars, and in particular, to a method for improving the size and appearance of scar tissue. The invention also relates to novel topical compositions for the treatment of scars and other skin symptoms and diseases.

BACKGROUND OF THE INVENTION When the skin or epidermis is cut or burned, scar tissue will form. In most cases, a small cut or burned area will result in a correspondingly small amount of scar tissue, which is usually not easily noticeable to an inadvertent observer. In other cases, when the wound area is large and/or too long, both the scar and scar tissue are obvious to the casual observer. This is not only embarrassing for patients with scars, but also uncomfortable for casual observers. This problem becomes more serious over time, and scar tissue tends to darken, thicken and bulge outward from the surface of the skin, so it becomes more obvious.

In the normal wound-healing or ulcer-healing process, there is abundant vascular network regeneration in the mature stage of the wound or ulcer, and collagen fibers gather into large bundles. If the shape of the connective tissue matrix changes during growth, development, and repair during wound and ulcer healing, a fine balance between collagen synthesis and degradation is required. Under normal circumstances, the synthesis and degradation of collagen are balanced. However, sometimes this maturation process cannot occur, so the scar tissue remains under the epithelial cells for a relatively long period of time, and even develops and becomes large. This is the clinical feature of hypertrophic scars.

Although the balance of scar formation and remodeling during skin wound healing is the basic process, excessive scar formation disorders are also very common and are a clinical problem that is difficult to control. Hypertrophic scars are excessive scars, which are defined as scars that grow larger than those required for normal wound healing. Hypertrophic scars can appear in many types of trauma, such as burns and sharp cuts. Hypertrophic scars increase, redness and itching increase. Scars can be sensitive to touch and other external pressures, and can form in every painful part of the body.

Hypertrophic scars often persist for a long time, sometimes even torturing a person's entire life. In the case of adults, hypertrophic scars usually transform into typical soft and pale scars in about a year. In addition to itching and relatively unsightly, if hypertrophic scars happen to extend to bones and joints, joint movement is often painful and restricted. In the past, this complication was overcome by covering with clothing, cosmetics, or avoiding contact with other people. This method is usually impossible and undesirable. Scar tissue and neighboring tissues usually become overly sensitive when in contact with clothing, and patients often do not cover the scar tissue, which damages their social image. In some cases, patients may not tolerate the use of cosmetics to cover scar tissue, which can also damage their social image. In other cases, the patient may need to wear a certain type or style of clothing that cannot cover the location of the scar tissue.

Many medical staff have recognized the problems associated with scar tissue, and currently treat the scar tissue as part of the overall treatment of the patient.

Many techniques for improving scars have been recommended. These include application of stress and treatment with, for example, hydrocortisone, collagen, vitamins such as vitamins E and A, and extracts of plant and animal origin. Some of these treatments have some effect, but all of these treatments are troublesome, inconvenient and even painful.

The use of pressure dressings is considered the most effective scar treatment method. Application of pressure significantly increases the activity of collagenase, which is capable of degrading and remodeling scar tissue, and is used in the body to maintain the balance between the formation and degradation of collagen during wound healing. However, the pressure dressing is bulky, making it very uncomfortable for the wearer, and it is often inconvenient to keep it in a location with scar tissue.

The use of steroids, such as cortisone, can also enhance the collagen degrading activity of collagenase. For large amounts of excessive scar tissue, such as hypertrophic scars or keloids, depending on the severity, doctors often recommend cortisone injections. In less severe cases, cortisone ointment or cortisone plaster shows a moderate effect. However, the ointment is often inconvenient to use because it gets very dirty, sticks to the clothes and causes the clothes to fade. There are also disadvantages to the use of tape, because it often makes the diseased area wet and fall from the area. In addition, cortisone ointment needs to be rubbed or massaged on the scar. It may be painful for some people. Cortisone injections are also painful for patients.

Vitamins such as vitamin E treatment are believed to reduce collagen adhesion during wound healing and have been used to soften scars. Cutting through the half of the vitamin E capsule and squeezing out the oil is the most common way to apply vitamin E to the wound. Obviously, vitamin E oil will stain the surroundings and it is annoying to cut the capsule in the middle. It is also known to add vitamins A and E to creams and lotions, but these creams and lotions are often oily to the touch and do not dry out, so they often remain oily or take a long time to go Rub thoroughly into the skin. Furthermore, rubbing or massaging creams or oils on and/or within a certain scar tissue can be painful for some people.

In recent years, it has been found that applying silicone film or membrane to scars can increase the shrinkage of hypertrophic scars. However, the precise mechanism of the interaction of silicone glue with such scars is still unclear. Many commercially available products are used for this purpose, such as Dow Corning Silastic (Dow Corning Silastic) tablets, Cica-Care (Smith & Nephew), Epi-Derm (Biodermis), Nagosil (Nagor) and other products. These products are in the form of a molded silicone film with a thickness of 2-4 mm. In the treatment of hypertrophic scars, these membranes are placed on the scar and worn for a relatively long time, usually 3-12 months, until the scar neither shrinks nor regenerates. Recently published patents for this type of silicone adhesive film include US Patent Nos. 5,759,560; 5,891,076; 5,895,656 and 5,919,476.

The known silicone adhesive film is relatively hard and does not have sufficient adhesive force after being attached to the scar, so it is difficult to keep it fixed in place without some auxiliary forms. As a result, fixation, stockings, bandages, self-adhesive tapes or some devices are required to firmly stick these films to the skin. These membranes often absorb too much moisture and cause irritation of the diseased area. The silicone glue type film is sticky to the touch, in the inner main body, the contact surface and the outer surface of the main body. It is advantageous and desirable to make the contact surface of the main body sticky to the touch. However, it is undesirable that the outer surface of the main body feels sticky. The unfavorable reason for external stickiness is that clothes tend to stick to the adhesive film. There are several problems. One problem is that it often appears that the force of the adhesive film adhering to clothing is greater than the force of adhering to the skin. Therefore, when the clothes are taken off, the adhesive film also comes off the body. Another problem is that the clothes stick to the film and hinder the normal range of movement. Another problem with adhesive films that are tacky to the touch is that they can easily get dirty quickly.

Other physical treatments available include surgery, X-ray therapy, and cryotherapy. This type of treatment is expensive or potentially dangerous, and is generally not recommended.

Therefore, physical therapy, compositions and/or articles containing medicaments that have a moderate effect in reducing, softening and reducing hypertrophic scars, these existing methods are expensive, inconvenient to use, difficult to apply, or just to obtain There is no obvious effect on the desired purpose.

SUMMARY OF THE INVENTION As mentioned above, the existing treatments for hypertrophic scars and keloids include surgery, mechanical compression, X-ray irradiation, cryotherapy, and various drugs such as steroids, vitamins, and the application of plant and animal extracts. Each of these methods has many disadvantages. Therefore, surgical removal of scar tissue is often incomplete, and may lead to the development of hypertrophic scars and keloids at the incision and suture point. X-ray therapy is the only effective therapy predicted so far. However, due to its potential to induce cancer, X-ray therapy is generally not recommended or accepted. The most commonly used treatment to control hypertrophic scars and keloids is to apply pressure, which seems to be effective in many cases. However, the usefulness of this therapy is limited because it generally depends on the size and location of the scar tissue on the body. Steroid injections are uncertain and often cause skin discoloration. The application of silicone-containing gels such as silicone films generally causes improvements in the appearance and size of the treated scars, but the mechanism of this healing is unclear, and as discussed above, this silicone gel film is not Convenience.

Therefore, the main objective of the present invention is to provide an effective and convenient composition that can improve the size and appearance of scars, especially hypertrophic scars.

In its broadest aspect, the present invention relates to a method for treating hypertrophic scars using an agent capable of reducing the size of a scar or improving its appearance, wherein the agent is contained in a membrane-forming carrier, which can be It is applied accurately and directly on the scar tissue of the lesion, and after drying, it becomes a substantially transparent film, so that the medicine stays in place. The film forming carrier of the present invention includes collodion, which includes a solution of collodion (nitrocellulose) in a 25/75 mixture of ethanol and ether, or an elastic collodion comprising a mixture of collodion, camphor and castor oil glue. This film-forming carrier is not oily or fatty. It is characterized in that the carrier is used together with vitamins or other plant or animal extracts or steroids. The film-forming carrier of the present invention can be directly applied to the application without friction or pressure. On the treated scars, this is different from the application of oily or fatty carriers that often cause pain in patients undergoing scar treatment.

Another aspect of the present invention is to provide a composition that can effectively reduce the size and appearance of hyperplastic scars, and can be easily and accurately applied directly to scars without oil and grease, or problems related to dressing and membranes , Only apply pressure or contact with silicone glue during application. In this aspect of the present invention, a carrier including collodion or elastic collodion film forming carrier is provided. This carrier includes a dermatologically effective steroid such as corticosteroid, which can be directly applied to scar tissue and dried. A transparent film containing the steroid agent is formed.

In another composition of the present invention described above, corticosteroids, silicone gum or vitamin E, or their mixtures are provided in a collodion or elastic collodion film forming carrier, and used to treat not only scars It also includes many skin symptoms and diseases.

Another aspect of the present invention is that a composition for treating hyperplastic scars to reduce the size of scars and improve its appearance is achieved by combining with dermatologically effective steroids such as hydrocortisone, silicone gum, and optional Vitamin E is combined into a single carrier, which can be directly applied to scar tissue, and for the first time appears as a multi-component pharmaceutical composition combined with the effective properties of the components that have been used alone. It has been found that steroids, silicone gum and vitamin E can be effectively mixed into membrane-forming carriers such as collodion or elastic collodion, and the composition does not need to be rubbed into the scar and directly applied to the scar tissue in a convenient manner . The composition forms a transparent film after drying, does not require dressing, tape, and does not have the disadvantages of oily or greasy agents that cause clothing to fade and need to be rubbed or massaged into the scar and remain on the treated area.

DETAILED DESCRIPTION OF THE INVENTION The method of the present invention is a method involving the application of a membrane-forming carrier to diseased scar tissue. The membrane-forming carrier contains one or more drugs (active ingredients) that can be applied to scar tissue and held in place by the membrane-forming carrier, and can reduce the size of hypertrophic scar tissue and/or improve its appearance. Therefore, the method of the present invention is a method of applying a membrane-forming carrier and one or more effective scar treatment drugs to hyperplastic scars. When the film-forming carrier dries, it forms a protective film on the place where the drug is applied to keep the active ingredient in contact with the scar and prevent the active ingredient from moving away from the original. The film former used in the method of the present invention is preferably collodion or elastic collodion. Collins is a solution of 4 grams of collodion (mainly nitrocellulose) in a mixture of 100 ml of 25 ml of ethanol and 75 ml of ether. Colloid gum is a colorless or light yellow, transparent or light milky white syrup-like liquid. The elastic collodion includes single collodion plus camphor and 3% castor oil (by weight). The elastic collodion is light yellow and contains a syrup-like liquid of 67% ether and approximately 22% absolute ethanol (by volume). When collodion or elastic collodion evaporates, a tough and colorless film is formed. The topical composition of the present invention also includes a solvent added to the carrier to dissolve the active ingredient. An example of a solvent that can be used is acetone.

In the method of the present invention, the active ingredient that can effectively treat hyperplastic scars is contained in the collodion or elastic collodion film forming carrier. Any effective, currently known or unknown active ingredient can be used in the method of the present invention. Such active ingredients include dermatologically active steroids, such as corticosteroids, vitamins and other plant and animal extracts known to treat scars, as well as silicone gels, including silicone gels that have been used in silicone films and sheets .

In the preparation of the topical composition used in the method of the present invention, conventional adjuvants such as propionic acid, propylene glycol, acetone and lactic acid, and conventional penetration enhancers such as erucic acid, oleic acid and bahemic acid can be added. ; Conventional buffers, preservatives, hydrophilic emulsifiers, lipophilic emulsifiers, sunscreens, fragrances, emollients, deodorants, moisturizers, etc. Pigments can also be optionally added to the composition of the present invention. Obviously, adjuvants that are harmful to scar tissue or surrounding skin should be avoided, as well as those that may react with the active ingredients incorporated into the film-forming carrier and/or reduce the effectiveness of the active ingredients. The current FDA monograph-approved formulations based on collodion can be used in such topical liquid compositions.

In the method of the present invention, it is preferable to use any commonly used applicator for applying the composition to the skin, such as a brush, roller or eye drop device, to facilitate the application of the collodion-based composition to the scar tissue to be treated. It is also possible to apply the composition by filling a porous base material with the composition and applying the composition to the scar, or the porous base material includes an adhesive that fixes the porous base material to the skin near the scar, and wherein the film-forming object and The active ingredient is placed on the scar to be treated. The composition used in the method of the present invention is a relatively viscous liquid, which can be directly and accurately applied to scar tissue without the need to apply additional force or friction like some oily or greasy ones used previously. Therefore, it is believed that the use of collodion-based membrane formations with one or more drugs for treating hyperplastic scars is a novel use.

The second aspect of the present invention is to provide a composition for treating hyperplastic scars so as to reduce the size of scars or improve the appearance of scars. In this aspect of the invention, an active ingredient in the form of a steroid is added to a collodion type film-forming carrier. Therefore, it has been found that dermatological active ingredients such as hydrocortisone, betamethasone and any other known corticosteroids that can be applied topically, as well as its pharmaceutically acceptable salts, including chloride and acetate It is added to the collodion film-forming carrier in an amount of about 0.25% to about 70% by weight to produce a composition that can be conveniently and directly applied to the scar tissue to be treated. The composition forms a transparent film after drying, and keeps the steroid active ingredients in contact with the scar tissue, and provides a beneficial and continuous steroid treatment effect. As mentioned above, adjuvants commonly used in topical compositions, including solvents, penetration enhancers, emollients, buffers, etc., can be added, as long as this addition does not negatively interfere with the effect of the steroid.

The present invention also relates to a topical composition that can be used to conveniently and effectively treat undesirable skin symptoms, including hypertrophic scars, eczema, psoriasis, atopic dermatitis and other immune skin diseases. In this aspect of the invention, topical active ingredients such as steroids, including corticosteroids, silicone gums, ie, non-volatile polysiloxanes, vitamins including vitamins A and E, or mixtures thereof, are incorporated into collodion Or the elastic collodion film is formed in the carrier. The concentration of each active ingredient will vary according to the skin disease to be treated, and can be easily selected from known dosage forms of active ingredients contained in other carriers such as lotions, grease, oil, or porous structures such as bandages, gauze, etc. To be sure. In general, the most practical concentration is 0.25 wt% to 75 wt%, but changes within the scope of the present invention are allowed.

Another aspect of the present invention is to provide a composition for improving the size and appearance of hypertrophic scars. This composition is also based on a collodion type film forming carrier. In this aspect of the present invention, three components that are active in improving hyperplastic scars and have been used on an individual basis are combined with a collodion type film-forming carrier, and the film-forming carrier is dried to become a transparent film covering the receiver. Treat the area and provide the base for the three components to act on the scar tissue and provide the desired improvement. Therefore, according to the present invention, the collodion type carrier incorporates dermatologically active steroids, silicone gum and optionally vitamin E.

The dermatologically active steroids that can be used are those described above, specifically, corticosteroids such as hydrocortisone, betamethasone, etc., including their pharmaceutically acceptable salts.

In addition, it was found that in addition to dermatologically active steroid ingredients, silicone gum can be further added to the combined species so that the collodion type carrier can still maintain the film forming effect and form a particularly advantageous composition. The silicone gums that can be added to the composition of the present invention are those that have been found to be effective in improving the appearance and size of hypertrophic scars. Silicone glue is a group of fully synthetic polymers, which includes a repeating group -SiR2O-, where R is substituted or unsubstituted such as alkyl, phenyl or vinyl. The simpler silicone glue is an oil with a very low melting point, and at the other extreme of the physical property specification is a highly cross-linked silicone glue that can form a rigid solid. The physical properties of the intermediate are silicone rubber elastomers, such as silicone rubber and rubber. Many silicone glues are used as wound dressings, as disclosed in U.S. Patent No. 4,838,253 assigned to Johnson and Johnson and U.S. Patent No. 4,991,574 assigned to Dow. Examples of commercially available silicone glues are under the trade name SILASTIC(R).

There is no final proof of how silicone glue acts on scar tissues to improve them. Based on the measurement including physical parameters related to the application of this silicone glue, the investigator concluded that the mode of action of silicone glue and scar treatment are not Including pressure, temperature, oxygen, tension or occlusion. As reported, a more suitable mechanism may include the hydration of the stratum corneum and the release of low-molecular-weight silicone gum fluid from the gel.

Any known silicone glue that has been previously used as a wound dressing as described above can be used in the composition of the present invention. Generally speaking, silicone rubber has a viscosity of 100-30000 centipoise at 25°C. Preferably, phenyltrimethicone such as Dow Corning 556 liquid or non-volatile polydimethylsiloxane can be used.

Although optional, it is preferable to include vitamin E (α-tocopherol) in the composition. In this most preferred embodiment, the three active ingredients known to treat hypertrophic scars on an individual basis are very useful in combination in a single membrane-forming carrier, and there is no adverse interaction between the ingredients. Useful compositions may include about 0.25-50% by weight of steroids such as hydrocortisone, preferably about 0.5-5% steroids; 2-70%, preferably 5-25% silicone gum and 0-25%, preferably 10 % Vitamin E. The remainder is the collodion type film forming carrier, no matter it is collodion or elastic collodion. Although collodion film forming support is preferred, other film forming supports can also be used. These examples include polyvinyl-pyrrolidone polymers and copolymers, polyacylated polymers and copolymers, and the like.

As mentioned above, other adjuvants can also be added to enhance the penetration of active ingredients, control the humidity on the scar tissue, provide antiseptic and antibacterial effects, and so on. In the most preferred embodiment, a small amount of xanthan gum may be added, which can both provide thickening properties and act as a dispersion enhancer for active substances including steroids such as hydrocortisone and silicone gum ingredients. If xanthan gum is added, its content should be about 0.5-4%, preferably about 0.75-2.5% by weight.

The composition of the present invention is considered a novel composition. Because of the carrier system, collodion type membrane-forming materials containing steroids and silicone glue have not been used to treat hypertrophic scars. Hydrocortisone can be used as a topical ointment or cream. Silicone glue can be applied in the form of liquid, ointment or as a bandage (it must be cut and adhered to the skin with a tape or other mechanism). The composition of the present invention combines the two Combine the active ingredients and disperse the agent on the matrix of the encapsulating dressing. When applied to the skin or by other methods, it is dried immediately, keeping the active ingredients in contact with the skin to exert their expected effects, and can be used at the end of the treatment It can be easily removed after or when applying the following medicine. The composition of the present invention does not require the help of other mechanisms, such as adhesive bandages, gauze, or medicine-impregnated cover sheets. The operation is conveniently completed by brushing the medical adhesive matrix to the scar area and allowing it to dry. The liquid matrix dries completely within one minute, resulting in a transparent, flexible closed bandage cover film. In addition to the easy application of the composition to the skin, other methods can also be used, including dispersive devices, which can roll the material onto the scar, and eye drop-type devices. It is important that the carrier containing the active ingredient of the present invention does not need to be rubbed or massaged on the scar area (rubbing or massage may be painful in some cases). In addition, the carrier forms a completely dry film after drying, and it does not stick to clothes. It has been found that the composition of the present invention can produce the best softening, shrinking and reducing hypertrophic scar effects when applied once or twice a day for 3-4 months.

EXAMPLES The following compositions are formulated as scar healing compositions and represent preferred embodiments of the present invention. The composition is prepared by adding the following ingredients to the carrier matrix (in this example, elastic collodion, USP): 10wt% silicone gum 5561wt% hydrocortisone hydrochloride 0.5wt% α-tocopherol (Vitamin E) 1.2wt% xanthan gum balance elastic collodion USP

This example is not intended to strictly limit the invention to the illustrated embodiment. It should be understood that the foregoing detailed description is for illustrative purposes only. Obviously, without departing from the spirit and scope of the present invention, any modifications and changes in the above are allowed. Therefore, only these restrictions stated in the appended claims should be complied with.